USPatent applicationPatented

Compositions and methods for immunooncology

Granted 26 Dec 2023 · 3 office actions

Assignee: Intellia Therapeutics

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Inventors: Morag Stewart, Hyungwook Lim, Yi Yang, Sarah Hesse +2 · Examiner: Kevin K Hill · AU 1631 · TC 1600

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Abstract

The present disclosure is directed to genome editing systems, reagents and methods for immunooncology.

Description

178 parts
›RELATED APPLICATIONS

This application claims priority to U.S. Provisional patent application No. 62/475,024, filed Mar. 22, 2017. The entire content of this application is incorporated herein by reference.

›SEQUENCE LISTING

The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Mar. 15, 2018, is named PAT057662-WO-PCT_SL.txt and is 3,460,141 bytes in size.

›BACKGROUND

CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats) evolved in bacteria as an adaptive immune system to defend against viral attack. Upon exposure to a virus, short segments of viral DNA are integrated into the CRISPR locus of the bacterial genome. RNA is transcribed from a portion of the CRISPR locus that includes the viral sequence. That RNA, which comprises a sequence complementary to the viral genome, mediates targeting of a Cas9 protein to the sequence in the viral genome. The Cas9 protein cleaves and thereby silences the viral target.

Recently, the CRISPR/Cas system has been adapted for genome editing in eukaryotic cells. The introduction of site-specific single-strand breaks (SSBs) or double-strand breaks (DSBs) allows for target sequence alteration through, for example, non-homologous end-joining (NHEJ) or homology-directed repair (HDR).

›SUMMARY · 1 of 7

In an aspect, the disclosure provides a gRNA molecule including a tracr and crRNA, wherein the crRNA includes a targeting domain that is complementary with a target sequence of a TET2 intron or TET2 intron-exon junction.

In an aspect, the disclosure provides a gRNA molecule, wherein the targeting domain is complementary to a sequence within a genomic region selected from: a) chr4:105146980-105190359; b) chr4:105190506-105233896; c) chr4:105237352-105241338; d) chr4:105241430-105242833; e) chr4:105242928-105243569; f) chr4:105243779-105259618; g) chr4:105259770-105261758; h) chr4:105261849-105269609; i) chr4:105269748-105272563; and j) chr4:105272919-105275047, wherein said genomic region is according to human reference genome hg38, for example, wherein the genomic region is chr4:105269748-105272563 (the intron between exon 9 and exon 10 of TET2).

In an aspect, the disclosure provides a gRNA molecule, wherein the targeting domain is complementary to a sequence within a genomic region selected from chr4:105270624-105270643; chr4:105270630-105270649; chr4:105271863-105271883; chr4:105271340-105271360; chr4:105271204-105271223; chr4:105271526-105271546; chr4:105270350-105270370; chr4:105270268-105270288; chr4:105272182-105272202; chr4:105272465-105272485; chr4:105271387-105271407; chr4:105272436-105272456; chr4:105271924-105271944; chr4:105272323-105272343; chr4:105272057-105272077; chr4:105272309-105272329; chr4:105272324-105272344; chr4:105272324-105272344; chr4:105271184-105271204; chr4:105271190-105271210; chr4:105271295-105271315; chr4:105271292-105271312; chr4:105271458-105271478; chr4:105270635-105270655; chr4:105271173-105271192; chr4:105271232-105271252; chr4:105271845-105271865; chr4:105271849-105271869; and chr4:105271056-105271076.

In an aspect, the disclosure provides a gRNA molecule, wherein the targeting domain is complementary to a sequence within a genomic region selected from chr4:105270624-105270643; chr4:105270630-105270649; chr4:105271387-105271407; chr4:105271924-105271944; chr4:105272323-105272343; chr4:105272057-105272077; chr4:105272309-105272329; chr4:105272324-105272344; chr4:105272324-105272344; chr4:105271184-105271204; chr4:105271190-105271210; chr4:105271295-105271315; chr4:105271292-105271312; chr4:105271458-105271478; chr4:105270635-105270655; chr4:105271173-105271192; chr4:105271232-105271252; and chr4:105271056-105271076.

In an aspect, the disclosure provides a gRNA molecule, wherein the targeting domain is complementary to a sequence within a genomic region selected from chr4:105271863-105271883; chr4:105271340-105271360; chr4:105271204-105271223; chr4:105271526-105271546; chr4:105270350-105270370; chr4:105270268-105270288; chr4:105272182-105272202; and chr4:105272465-105272485. In some embodiments, the gRNA molecule is capable of generating the editing repair pattern described in Table 22 and/or >75% indel frequencies as described in Table 23.

In an aspect, the disclosure provides a gRNA molecule, wherein the targeting domain is complementary to a sequence within a genomic region selected from chr4:105271340-105271360; chr4:105271526-105271546; chr4:105270350-105270370; chr4:105270268-105270288; chr4:105272182-105272202; and chr4:105272465-105272485. In some embodiments, the gRNA molecule is capable of generating the editing repair pattern described in Table 22 and/or >80% indel frequencies as described in Table 23.

In an aspect, the disclosure provides a gRNA molecule, wherein the targeting domain is complementary to a sequence within a genomic region selected from chr4:105270624-105270643, chr4:105270630-105270649, and chr4:105271863-105271883. In an aspect, including in any of the previous aspects, a gRNA molecule of the disclosure includes a targeting domain includes, e.g., consists of, any one of SEQ ID NO: 1000 to SEQ ID NO: 10514, e.g., of Table 1 or Table 2, e.g., includes, e.g., consists of, any one of SEQ ID NO: 10102 to SEQ ID NO: 10324.

In an aspect of the gRNA molecule, including in any of the previous aspects, a gRNA molecule of the disclosure includes a targeting domain that includes, e.g., consists of, a targeting domain sequence listed in Table 2, for example, includes, e.g., consists of, any one of SEQ ID NO: 10148, SEQ ID NO: 10184, SEQ ID NO: 10185, SEQ ID NO: 10188, SEQ ID NO: 10209, SEQ ID NO: 10212, SEQ ID NO: 10317, SEQ ID NO: 10318, SEQ ID NO: 10187, SEQ ID NO: 10224, SEQ ID NO: 10292, SEQ ID NO: 10149, SEQ ID NO: 10177, SEQ ID NO: 10151, SEQ ID NO: 10225 or SEQ ID NO: 10509.

In an aspect of the gRNA, including in any of the previous aspects, a gRNA molecule of the disclosure includes a targeting domain that comprises or consists of SEQ ID NO: 10148, 10149, 10206, 10191, 10515, 10203, 10259, 10136, 10314, 10234, 10290, 10233, 10209, 10224, 10212, 10317, 10318, 10225, 10184, 10185, 10188, 10187, 10292, 10151, 10509, 10281, 10299, 10301, or 10177; or a fragment thereof.

In an aspect of the gRNA, including in any of the previous aspects, a gRNA molecule of the disclosure includes a targeting domain that comprises or consists of SEQ ID NO: 10148, 10149, 10290, 10209, 10224, 10212, 10317, 10318, 10225, 10184, 10185, 10188, 10187, 10292, 10151, 10509, 10281, or 10177; or a fragment thereof.

In an aspect of the gRNA, including in any of the previous aspects, a gRNA molecule of the disclosure includes a targeting domain that comprises or consists of SEQ ID NO: 10206, 10191, 10515, 10203, 10259, 10136, 10314, or 10234; or a fragment thereof.

In an aspect of the gRNA, including in any of the previous aspects, a gRNA molecule of the disclosure includes a targeting domain that comprises or consists of SEQ ID NO: 10191, 10203, 10259, 10136, 10314, or 10234; or a fragment thereof. In some embodiments, the gRNA molecule is capable of generating the editing repair pattern described in Table 22 and/or >75% indel frequencies as described in Table 23.

In an aspect of the gRNA, including in any of the previous aspects, a gRNA molecule of the disclosure includes a targeting domain that comprises or consists of SEQ ID NO: 10148, SEQ ID NO: 10149, or SEQ ID NO: 10206; or a fragment thereof. In some embodiments, the gRNA molecule is capable of generating the editing repair pattern described in Table 22 and/or >80% indel frequencies as described in Table 23.

›SUMMARY · 2 of 7

In some embodiments, the gRNA molecules are capable of generating the editing repair pattern described in Table 22 and/or the indel frequencies described in Table 23. In an aspect of the gRNA molecule, including in any of the previous aspects, the targeting domain includes 17, 18, 19 or, 20 consecutive nucleic acids of any one of the recited targeting domain sequences. In an aspect, including in any of the previous aspects, the targeting domain consists of 17, 18, 19, or 20 consecutive nucleic acids of any one of the recited targeting domain sequences. In an aspect, the 17, 18, 19, or 20 consecutive nucleic acids of any one of the recited targeting domain sequences are the 17, 18, 19, or 20 consecutive nucleic acids disposed at the 3′ end of the recited targeting domain sequence. In another aspect, the 17, 18, 19, or 20 consecutive nucleic acids of any one of the recited targeting domain sequences are the 17, 18, 19, or 20 consecutive nucleic acids disposed at the 5′ end of the recited targeting domain sequence. In another aspect, the 17, 18, 19, or 20 consecutive nucleic acids of any one of the recited targeting domain sequences do not include either the 5′ or 3′ nucleic acid of the recited targeting domain sequence.

In an aspect of the gRNA molecule, including in any of the previous aspects, the targeting domain consists of the recited targeting domain sequence.

In an aspect of the gRNA molecule, including in any of the previous aspects, a portion of the crRNA and a portion of the tracr hybridize to form a flagpole including SEQ ID NO: 50 or SEQ ID NO: 51. In an aspect of the gRNA molecule, including in any of the previous aspects, the flagpole further includes a first flagpole extension, located 3′ to the crRNA portion of the flagpole, wherein said first flagpole extension includes SEQ ID NO: 55. In an aspect of the gRNA molecule, including in any of the previous aspects, the flagpole further includes a second flagpole extension located 3′ to the crRNA portion of the flagpole and, if present, the first flagpole extension, wherein said second flagpole extension includes SEQ ID NO: 57.

In an aspect of the gRNA molecule, including in any of the previous aspects, the tracr includes: (a) SEQ ID NO: 87, optionally further including, at the 3′ end, an additional 1, 2, 3, 4, 5, 6, or 7 uracil (U) nucleotides; (b) SEQ ID NO: 65; or (c) SEQ ID NO: 84.

In an aspect of the gRNA molecule, including in any of the previous aspects, the crRNA portion of the flagpole includes SEQ ID NO: 79 or SEQ ID NO: 80.

In an aspect of the gRNA molecule, including in any of the previous aspects, the tracr includes SEQ ID NO: 53 or SEQ ID NO: 54, and optionally, if a first flagpole extension is present, a first tracr extension, disposed 5′ to SEQ ID NO: 53 or SEQ ID NO: 54, said first tracr extension including SEQ ID NO: 56.

In an aspect of the gRNA molecule, including in any of the previous aspects, the targeting domain and the tracr are disposed on separate nucleic acid molecules.

In an aspect of the gRNA molecule, including in any of the previous aspects, the crRNA includes, from 5′ to 3′, [targeting domain]-: a) SEQ ID NO: 50; b) SEQ ID NO: 51; c) SEQ ID NO: 77; d) SEQ ID NO: 78; e) SEQ ID NO: 79; f) SEQ ID NO: 80; or g) SEQ ID NO: 81.

In an aspect of the gRNA molecule, including in any of the previous aspects, the tracr includes, from 5′ to 3′: a) SEQ ID NO: 53; b) SEQ ID NO: 54; c) SEQ ID NO: 82; d) SEQ ID NO: 83; e) SEQ ID NO: 65; f) SEQ ID NO: 84; g) SEQ ID NO: 87; h) SEQ ID NO: 76; i) SEQ ID NO: 85; j) SEQ ID NO: 86; k) any of a) to j), above, further including, at the 3′ end, at least 1, 2, 3, 4, 5, 6 or 7 uracil (U) nucleotides, e.g., 1, 2, 3, 4, 5, 6, or 7 uracil (U) nucleotides; 1) any of a) to k), above, further including, at the 3′ end, at least 1, 2, 3, 4, 5, 6 or 7 adenine (A) nucleotides, e.g., 1, 2, 3, 4, 5, 6, or 7 adenine (A) nucleotides; or m) any of a) to 1), above, further including, at the 5′ end (e.g., at the 5′ terminus), at least 1, 2, 3, 4, 5, 6 or 7 adenine (A) nucleotides, e.g., 1, 2, 3, 4, 5, 6, or 7 adenine (A) nucleotides.

In an aspect of the gRNA molecule, including in any of the previous aspects, the targeting domain and the tracr are disposed on separate nucleic acid molecules, and wherein the nucleic acid molecule including the targeting domain includes SEQ ID NO: 79, optionally disposed immediately 3′ to the targeting domain, and the nucleic acid molecule including the tracr includes, e.g., consists of, SEQ ID NO: 65.

In an aspect of the gRNA molecule, including in any of the previous aspects, the targeting domain and the tracr are disposed on a single nucleic acid molecule, and wherein the tracr is disposed 3′ to the targeting domain. In an aspect of the gRNA molecule, including in any of the previous aspects involving a sgRNA, the gRNA molecule further includes a loop, disposed 3′ to the targeting domain and 5′ to the tracr, for example a loop that includes SEQ ID NO: 52.

In an aspect of the gRNA molecule, including in any of the previous aspects, the gRNA molecule includes, from 5′ to 3′, [targeting domain]-: (a) SEQ ID NO: 71; (b) SEQ ID NO: 72; (c) SEQ ID NO: 73; (d) SEQ ID NO: 74; (e) SEQ ID NO: 75; or (f) any of (a) to (e), above, further including, at the 3′ end, 1, 2, 3, 4, 5, 6 or 7 uracil (U) nucleotides.

In an aspect of the gRNA molecule, including in any of the previous aspects, the targeting domain and the tracr are disposed on a single nucleic acid molecule, and wherein said nucleic acid molecule includes, e.g., consists of, said targeting domain and SEQ ID NO: 71, optionally disposed immediately 3′ to said targeting domain.

In an aspect of the gRNA molecule, including in any of the previous aspects, the targeting domain and the tracr are disposed on a single nucleic acid molecule, and wherein said nucleic acid molecule includes, e.g., consists of, said targeting domain and SEQ ID NO: 75, optionally disposed immediately 3′ to said targeting domain.

In an aspect of the gRNA molecule, including in any of the previous aspects, one, or optionally more than one, of the nucleic acid molecules including the gRNA molecule includes: a) a, e.g., three, phosphorothioate modification(s) at the 3′ end of said nucleic acid molecule or molecules; b) a, e.g., three, phosphorothioate modification(s) at the 5′ end of said nucleic acid molecule or molecules; c) a, e.g., three, 2′-O-methyl modification(s) at the 3′ end of said nucleic acid molecule or molecules; d) a, e.g., three, 2′-O-methyl modification(s) at the 5′ end of said nucleic acid molecule or molecules; e) a 2′ O-methyl modification at each of the 4th-to-terminal, 3rd-to-terminal, and 2nd-to-terminal 3′ residues of said nucleic acid molecule or molecules; or f) any combination thereof.

›SUMMARY · 3 of 7

In an aspect of the gRNA molecule, including in any of the previous aspects, when a CRISPR system (e.g., an RNP as described herein) including the gRNA molecule is introduced into a cell, an indel is formed at or near the target sequence complementary to the targeting domain of the gRNA molecule, for example, an indel that includes a deletion of greater than 10 nucleotides, e.g., 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, or 35 nucleotides.

In an aspect of the gRNA molecule, including in any of the previous aspects, when a CRISPR system (e.g., an RNP as described herein) including the gRNA molecule is introduced into a population of cells, an indel is formed at or near the target sequence complementary to the targeting domain of the gRNA molecule in at least about 40%, e.g., at least about 50%, e.g., at least about 60%, e.g., at least about 70%, e.g., at least about 80%, e.g., at least about 90%, e.g., at least about 95%, e.g., at least about 96%, e.g., at least about 97%, e.g., at least about 98%, e.g., at least about 99%, of the cells of the population, for example, as measured by next generation sequencing (NGS). In an aspect of the gRNA molecule, including in any of the previous aspects, the indel that includes a deletion of greater than 10 nucleotides, e.g., 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, or 35 nucleotides is detected in at least about 5%, e.g., at least about 10%, 15%, 20%, 25%, 30% or more of the cells of the population, for example, as measured by next generation sequencing (NGS).

In an aspect of the gRNA molecule, including in any of the previous aspects, when a CRISPR system (e.g., an RNP as described herein) including the gRNA molecule is introduced into a cell, expression of TET2, e.g., at least one isoform of TET2, is reduced or eliminated in said cell.

In an aspect of the gRNA molecule, including in any of the previous aspects, when a CRISPR system (e.g., an RNP as described herein) including the gRNA molecule is introduced into a cell, a function, e.g., a catalytic function, of TET2 is reduced or eliminated in said cell.

In an aspect of the gRNA molecule, including in any of the previous aspects, the function, e.g., the catalytic function, of TET2 is reduced, e.g., by at least about 10%, 20%, 30%, 40% or 50%, but said function, e.g., said catalytic function, is not reduced by more than about 80%, e.g., is not eliminated, in said cell.

In an aspect of the gRNA molecule, including in any of the previous aspects, when a CRISPR system (e.g., an RNP as described herein) including the gRNA molecule is introduced into a cell, TET2 expression, e.g., expression of at least one TET2 isoform, and/or at least one TET2 function is not altered relative to the level of expression and/or function in the same type of cell but to which said CRISPR system is not introduced (e.g., an unaltered cell of the same type).

In an aspect of the gRNA molecule, including in any of the previous aspects, when a CRISPR system (e.g., an RNP as described herein) including the gRNA molecule is introduced into a cell, no off-target indels are formed in said cell, e.g., as detectible by next generation sequencing and/or a nucleotide insertional assay. In an aspect of the gRNA molecule, including in any of the previous aspects, when a CRISPR system (e.g., an RNP as described herein) including the gRNA molecule is introduced into a population of cells, an off-target indel is detected in no more than about 5%, e.g., no more than about 1%, e.g., no more than about 0.1%, e.g., no more than about 0.01%, of the cells of the population of cells e.g., as detectible by next generation sequencing and/or a nucleotide insertional assay.

In some embodiments, when a CRISPR system (e.g., an RNP as described herein) including the gRNA molecule (e.g., described herein) is introduced into a cell, e.g., a T cell, a non-naturally occurring indel at or near the target sequence of a gRNA described herein is formed, e.g., an indel comprising a non-naturally occurring indel as described in Table 22 is formed. In some embodiments, when a CRISPR system (e.g., an RNP as described herein) including the gRNA molecule (e.g., described herein) is introduced into a population of cells, e.g., a population of T cells, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of the cells of the population comprise one or more non-naturally occurring indels at or near the target sequence of a gRNA described herein, e.g., comprise one or more non-naturally occurring indels selected from the indels described in Table 22 (e.g., the indels described in Table 2 associated with a gRNA targeting domain sequence).

In some embodiments, when a CRISPR system (e.g., an RNP as described herein) including a gRNA molecule (e.g., described herein) and a template nucleic acid molecule (e.g., as described herein) is introduced into a cell, e.g., a T cell, a cell comprising heterologous sequence inserted at or near the target sequence of a gRNA is formed. In some embodiments, the heterologous sequence comprises sequence encoding a CAR, e.g., as described herein. In some embodiments, the heterologous sequence comprises sequence encoding a CAR, e.g., as described herein, operably linked to sequence encoding a promoter, e.g., an EF1-alpha promoter, e.g., as described herein. In an aspect the disclosure provides a composition including a first gRNA molecule of any of the preceding gRNA aspects and embodiments. In an aspect, the composition further includes a Cas9 molecule, for example, a Cas9 molecule that includes, e.g., consists of, any one of SEQ ID NO: 90 or SEQ ID NO: 111 to SEQ ID NO: 121 or SEQ ID NO: 123, or for example, an active or inactive S. pyogenes Cas9.

In an aspect of the composition, including in any of the previous composition aspects, the first gRNA molecule and Cas9 molecule are present in a ribonuclear protein complex (RNP).

›SUMMARY · 4 of 7

In an aspect of the composition, including in any of the previous composition aspects, the composition further includes a template nucleic acid, for example, a template nucleic acid that is double-stranded or single stranded, or for example, wherein the template nucleic acid is or is included in a vector, for example, a lentivirus vector, and AAV vector, an adenovirus vector, a plasmid, a minicircle or a nanoplasmid. In an aspect of the composition, including in any of the previous composition aspects, the template nucleic acid includes at least one (e.g., at least a 5′ or at least a 3′) homology arm, and wherein said homology arm includes sequence homologous to sequence of a TET2 intron. In an aspect of the composition, including in any of the previous composition aspects, the template nucleic acid includes both a 5′ and a 3′ homology arm, and wherein at least one of the homology arms includes sequence homologous to sequence of a TET2 intron. In an aspect of the composition, including in any of the previous composition aspects, the composition the template nucleic acid includes nucleic acid encoding a chimeric antigen receptor (CAR), for example, a CAR as described herein. In aspects, the CAR is: (a) a CD19 CAR, e.g., as described in herein; or (b) a BCMA CAR, e.g., as described herein. In aspects, the CAR is a CD19 CAR including an antigen binding domain including any one of SEQ ID NO: 160 to SEQ ID NO: 172 or SEQ ID NO: 175. In aspects, the CAR is a CD19 CAR and includes any one of SEQ ID NO: 185 to SEQ ID NO: 197. In other aspects, the CAR is a BCMA CAR including an antigen binding domain including any one of SEQ ID NO: 239 to SEQ ID NO: 412. In aspects, the CAR is a BCMA CAR and includes any one of SEQ ID NO: 849 to SEQ ID NO: 863 or SEQ ID NO: 879 to SEQ ID NO: 899, e.g., includes SEQ ID NO: 859. In an aspect of the composition, including in any of the previous composition aspects, the composition includes a template nucleic acid that includes a promotor, e.g., an EF1-alpha promoter, operably linked to the nucleic acid sequence encoding the CAR.

In an aspect of the composition, including in any of the previous composition aspects, the composition further includes at least one additional gRNA molecule (e.g., a second gRNA molecule; a second gRNA molecule and a third gRNA molecule; or a second gRNA molecule, a third gRNA molecule, and a fourth gRNA molecule), and wherein each gRNA molecule of the composition is complementary to a different target sequence. In an aspect, the at least one additional gRNA molecule, e.g., a second gRNA molecule, the third gRNA molecule (if present), and the fourth gRNA molecule (if present), are complementary to target sequences within the same TET2 intron. In another aspect, the first gRNA molecule, the second gRNA molecule, the third gRNA molecule (if present), and the fourth gRNA molecule (if present) are complementary to target sequence within different genes, for example, the first gRNA molecule is a gRNA molecule of any of the previous gRNA aspects and embodiments (e.g., as described herein), and the second gRNA molecule includes a targeting domain complementary to a target sequence of an inhibitory molecule (e.g., PDCD1), a component of the T cell receptor (e.g., TRAC or TRBC), B2M, or CIITA.

In an aspect of the composition, including in any of the previous composition aspects, the composition is formulated in a medium suitable for electroporation, for example, wherein each of said gRNA molecules is in a RNP complex with a Cas9 molecule described herein, and wherein each of said RNP complexes is at a concentration of less than about 10 uM, e.g., less than about 3 uM, e.g., less than about 1 uM, e.g., less than about 0.5 uM, e.g., less than about 0.3 uM, e.g., less than about 0.1 uM.

In an aspect, the disclosure provides a nucleic acid sequence that encodes a gRNA molecule of any of the preceding gRNA aspects and embodiments or a, e.g., all, components of a composition of any of the preceding composition aspects and embodiments.

In an aspect, the disclosure provides a vector including a nucleic acid of any of the preceding nucleic acid aspects and embodiments, for example, wherein in the vector is selected from the group consisting of a lentiviral vector, an adenoviral vector, an adeno-associated viral (AAV) vector, a herpes simplex virus (HSV) vector, a plasmid, a minicircle, a nanoplasmid, and an RNA vector.

In an aspect, the disclosure provides a method of altering e.g., altering the structure, e.g., sequence of, a target sequence of a cell, including contacting said cell with: a) a gRNA molecule, e.g., more than one gRNA molecule, of any of the preceding gRNA aspects and embodiments and a Cas9 molecule; b) a gRNA molecule, e.g., more than one gRNA molecule, of any of the preceding gRNA aspects and embodiments and nucleic acid encoding a Cas9 molecule; c) nucleic acid encoding a gRNA molecule, e.g., more than one gRNA molecule, of any of the preceding gRNA aspects and embodiments and a Cas9 molecule; d) nucleic acid encoding a gRNA molecule, e.g., more than one gRNA molecule, of any of the preceding gRNA aspects and embodiments and nucleic acid encoding a Cas9 molecule; e) any of a) to d), above, and a template nucleic acid, e.g., a template nucleic acid as described in any of the preceding aspects and embodiments, e.g., as described herein; g) the composition of any of the preceding composition aspects and embodiments; or h) the vector of any of the preceding vector aspects and embodiments.

In an aspect of the method, including in any of the previous method aspects, the gRNA molecule of any of the preceding gRNA aspects and embodiments (or nucleic acid encoding the gRNA molecule of any of the preceding gRNA aspects and embodiments), and the Cas9 molecule or nucleic acid encoding the Cas9 molecule, are formulated in a single composition.

In an aspect of the method, including in any of the previous method aspects, when the composition includes a template nucleic acid, e.g., a template nucleic acid as described in of any of the preceding aspects and embodiments (e.g., as described herein), the template nucleic acid is formulated in a separate composition from the gRNA molecule of any of the preceding gRNA aspects and embodiments (or nucleic acid encoding the gRNA molecule of any of the preceding gRNA aspects and embodiments) and the Cas9 molecule or nucleic acid encoding the Cas9 molecule. In an aspect the more than one compositions are delivered (to a cell) sequentially.

›SUMMARY · 5 of 7

In an aspect of the method, including in any of the previous method aspects, the method results in insertion of at least a portion of the template nucleic acid at or near the target sequence of the gRNA molecule of any of the preceding gRNA aspects and embodiments. In an aspect, insertion occurs at only at one allele.

In an aspect, the disclosure provides a method of engineering a cell to express a chimeric antigen receptor (CAR), including: (a) introducing into said cell a CRISPR system including a gRNA molecule of any of the preceding gRNA aspects and embodiments or a composition of any of the preceding composition aspects and embodiments; and (b) introducing into said cell a template nucleic acid including nucleic acid sequence encoding a CAR; wherein said nucleic acid sequence encoding a CAR is integrated into the genome, e.g., optionally at only a single allele of the genome, at or near the target sequence of said gRNA molecule. In an aspect, the method further includes introducing into said cell one or more CRISPR systems including one or more gRNA molecules complementary to a target sequence of an inhibitory molecule, a component of the T cell receptor, B2M and/or CIITA.

In an aspect of the method, including in any of the previous method aspects, the cell is an animal cell, for example, a mammalian, primate, or human cell, for example, an immune effector cell (e.g., a population of immune effector cells), for example, a T cell or NK cell, e.g., a T cell, e.g., a CD4+ T cell, a CD8+ T cell, or a combination thereof.

In an aspect of the method, including in any of the previous method aspects, the CAR is a CAR described herein, for example: (a) a CD19 CAR, e.g., as described in herein; or (b) a BCMA CAR, e.g., as described herein. In aspects, the CAR is: (a) a CD19 CAR, e.g., as described in herein; or (b) a BCMA CAR, e.g., as described herein. In aspects, the CAR is a CD19 CAR including an antigen binding domain including any one of SEQ ID NO: 160 to SEQ ID NO: 172 or SEQ ID NO: 175. In aspects, the CAR is a CD19 CAR and includes any one of SEQ ID NO: 185 to SEQ ID NO: 197. In other aspects, the CAR is a BCMA CAR including an antigen binding domain including any one of SEQ ID NO: 239 to SEQ ID NO: 412. In aspects, the CAR is a BCMA CAR and includes any one of SEQ ID NO: 849 to SEQ ID NO: 863 or SEQ ID NO: 879 to SEQ ID NO: 899, e.g., includes SEQ ID NO: 859.

In an aspect of the method, including in any of the previous method aspects, the cell is autologous or allogeneic with respect to a patient to be administered said cell.

In an aspect, the disclosure provides a cell as described herein, for example, a cell altered by the method of any of the herein method aspects and embodiments (e.g., by a method described herein). In aspects, the cell includes a first gRNA molecule of any of the preceding gRNA aspects and embodiments (e.g., as described herein), or a composition of any of the preceding composition aspects and embodiments (e.g., as described herein), a nucleic acid, e.g., as described herein, or a vector of any of the preceding vector aspects and embodiments. In aspects, the cell is an animal cell, e.g., a mammalian, primate, or human cell. In aspects, the cell is an immune effector cell (e.g., a population of immune effector cells), e.g., a T cell or NK cell, e.g., a T cell, e.g., a CD4+ T cell, a CD8+ T cell, or a combination thereof.

In an aspect of the cell, including in any of the previous cell aspects, the cell has reduced or eliminated expression of an inhibitory molecule, a component of the T cell receptor (e.g., TRAC, TRBC1, TRBC2, CD3E, CD3D, or CD3G), B2M, CIITA, or combinations thereof, e.g., relative to an unmodified cell of the same type.

In an aspect of the cell, including in any of the previous cell aspects, the cell includes nucleic acid sequence encoding a chimeric antigen receptor (CAR) (e.g., a CAR as described herein) integrated into the genome at a TET2 intron or intron-exon junction, e.g., integrated at only a single allele.

In an aspect of the cell, including in any of the previous cell aspects, the cell includes reduced or eliminated TET2 expression, e.g., expression of at least one TET2 isoform, and/or reduced or eliminated function of TET2, e.g., at least one function of TET2, e.g., catalytic function of TET2, relative to the level of expression and/or function of an unaltered cell of the same cell type.

In an aspect of the cell, including in any of the previous cell aspects, the cell is a T cell and exhibits: (a) enhanced proliferative capacity; (b) enhanced cytotoxicity; (c) a less-exhausted phenotype (e.g., reduced expression of an inhibitory molecule, e.g., PD1, TIM3, LAG3, PD-L1, or combinations thereof); or (d) a Tscm phenotype (e.g., is CD45RA+CD62L+CD27+CD95+), relative to an unaltered cell of similar type.

In an aspect of the cell, including in any of the previous cell aspects, the cell is autologous with respect to a patient to be administered said cell. In other aspects of the cell, including in any of the previous cell aspects, the cell is allogeneic with respect to a patient to be administered said cell.

In an aspect, the disclosure provides a modified cell, which has reduced or eliminated expression and/or function of TET2, and includes heterologous nucleic acid sequence (e.g., nucleic acid sequence encoding a chimeric antigen receptor, e.g., as described herein) integrated at a site within a TET2 intron, wherein said site within a TET2 intron is selected from: a) chr4:105146980-105190359; b) chr4:105190506-105233896; c) chr4:105237352-105241338; d) chr4:105241430-105242833; e) chr4:105242928-105243569; f) chr4:105243779-105259618; g) chr4:105259770-105261758; h) chr4:105261849-105269609; i) chr4:105269748-105272563; and j) chr4:105272919-105275047, wherein the coordinates above are according to hg38.

In an aspect of the cell, including in any of the previous cell aspects, the cell has reduced or eliminated expression and/or function of a component of the T cell receptor, B2M, CIITA or a combination thereof, relative to an unmodified cell of the same type.

›SUMMARY · 6 of 7

In some embodiments, including in any of the previous cell aspects and embodiments, the cell, e.g., the T cell, comprises a non-naturally occurring indel at or near the target sequence of a gRNA described herein, e.g., comprises an indel comprising a non-naturally occurring indel as described in Table 22. In some embodiments, including in any of the previous cell aspects and embodiments, the disclosure provides a population of cells, e.g., a population of T cells, wherein at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of the cells of the population comprise one or more non-naturally occurring indels at or near the target sequence of a gRNA described herein, e.g., comprise one or more non-naturally occurring indels selected from the indels described in Table 22 (e.g., the indels described in Table 2 associated with a gRNA targeting domain sequence).

In some embodiments, the disclosure provides a cell comprising heterologous sequence inserted at or near the target sequence of a gRNA, e.g., a gRNA described herein. In some embodiments, the heterologous sequence comprises sequence encoding a CAR, e.g., as described herein. In some embodiments, the heterologous sequence comprises sequence encoding a CAR, e.g., as described herein, operably linked to sequence encoding a promoter, e.g., an EF1-alpha promoter, e.g., as described herein. In preferred embodiments, the CAR in expressed in said cell.

In an aspect, the disclosure provides a method of providing an anti-tumor immunity in a subject, the method including administering to the subject an effective amount of a cell of any of the preceding cell aspects and embodiments (e.g., as described herein).

In an aspect, the disclosure provides a method of treating a subject having a disease associated with expression of a tumor antigen, e.g., a proliferative disease, a precancerous condition, a cancer, and a non-cancer related indication associated with expression of the tumor antigen, the method including administering to the subject an effective amount of a cell of any of the preceding cell aspects and embodiments (e.g., as described herein), for example, wherein the disease associated with expression of a tumor antigen is cancer or a non-cancer related indication, for example, wherein the disease is cancer, for example, a cancer selected from colon cancer, rectal cancer, renal-cell carcinoma, liver cancer, non-small cell carcinoma of the lung, cancer of the small intestine, cancer of the esophagus, melanoma, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, non-Hodgkin's lymphoma, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, solid tumors of childhood, cancer of the bladder, cancer of the kidney or ureter, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain stem glioma, pituitary adenoma, Kaposi's sarcoma, epidermoid cancer, squamous cell cancer, T-cell lymphoma, environmentally induced cancers, chronic lymphocytic leukemia (CLL), acute leukemias, acute lymphoid leukemia (ALL), B-cell acute lymphoid leukemia (B-ALL), T-cell acute lymphoid leukemia (T-ALL), chronic myelogenous leukemia (CML), acute myeloid leukemia (AML), B cell prolymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B cell lymphoma, follicular lymphoma, hairy cell leukemia, small cell- or a large cell-follicular lymphoma, malignant lymphoproliferative conditions, MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndrome, Hodgkin's lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenstrom macroglobulinemia, and pre-leukemia, combinations of said cancers, and metastatic lesions of said cancers.

In an aspect of the method, including in any of the previous method aspects, the method further includes administering a chemotherapeutic agent, for example, cyclophosphamide, fludarabine, or cyclophosphamide and fludarabine.

In an aspect of the method, including in any of the previous method aspects, the method includes administering a lympho-depleting agent or immunosuppressant prior to administering to the subject an effective amount of the cell of any of the preceding cell aspects and embodiments (e.g., as described herein).

In an aspect, the disclosure provides a population of cells including the cell of any of the previous cell aspects and embodiments (e.g., as described herein), wherein at least about 30% of the cells, e.g., at least about 40%, 50%, 60%, 70%, 80% or 90% of the cells, are a cell of any of the preceding cell aspects and embodiments (e.g., as described herein).

In an aspect, the disclosure provides a gene editing system which binds a sequence of a TET2 intron or intron-exon junction, for example, wherein the sequence of a TET2 intron or intron-exon junction is a sequence within a genomic region selected from: a) chr4:105146980-105190359; b) chr4:105190506-105233896; c) chr4:105237352-105241338; d) chr4:105241430-105242833; e) chr4:105242928-105243569; f) chr4:105243779-105259618; g) chr4:105259770-105261758; h) chr4:105261849-105269609; i) chr4:105269748-105272563; and j) chr4:105272919-105275047, wherein said genomic region is according to hg38, for example, wherein the genomic region is chr4:105269748-105272563. In an aspect, the gene editing system is a zinc finger nuclease (ZFN) gene editing system, a TALEN gene editing system, a CRISPR gene editing system, or a meganuclease gene editing system. In an aspect, the gene editing system further includes a template nucleic acid (e.g., as described herein), for example, a template nucleic acid including nucleic acid sequence encoding a CAR (e.g., as described herein). In an aspect of the gene editing system, including in any of the previous gene editing system aspects, when said gene editing system (and/or nucleic acid sequence encoding one or more components of the gene editing system) is introduced into a cell, the nucleic acid sequence encoding the CAR is integrated into the genome of said cell at or near the sequence of a TET2 intron or intron-exon junction bound by said genome editing system.

›SUMMARY · 7 of 7

In an aspect, the disclosure provides a cell, modified by the gene editing system of any of the preceding gene editing system aspects and embodiments (e.g., as described herein).

In an aspect, the disclosure provides a cell including the gene editing system of any of the preceding gene editing system aspects and embodiments (e.g., as described herein).

In an aspect, the disclosure provides a gRNA molecule of any of the preceding gRNA aspects and embodiments (e.g., as described herein), a composition of any of the preceding composition aspects and embodiments (e.g., as described herein), a nucleic acid of any of the preceding nucleic acid aspects and embodiments (e.g., as described herein), a vector of any of the preceding vector aspects and embodiments (e.g., as described herein), a cell (or population of cells) of any of the preceding cell aspects and embodiments (e.g., as described herein), or a gene editing system of any of the preceding gene editing system aspects and embodiments (e.g., as described herein), for use as a medicament.

In an aspect, the disclosure provides a gRNA molecule of any of the preceding gRNA aspects and embodiments (e.g., as described herein), a composition of any of the preceding composition aspects and embodiments (e.g., as described herein), a nucleic acid of any of the preceding nucleic acid aspects and embodiments (e.g., as described herein), a vector of any of the preceding vector aspects and embodiments (e.g., as described herein), a cell (or population of cells) of any of the preceding cell aspects and embodiments (e.g., as described herein), or a gene editing system of any of the preceding gene editing system aspects and embodiments (e.g., as described herein), for use in the manufacture of a medicament.

In an aspect, the disclosure provides a gRNA molecule of any of the preceding gRNA aspects and embodiments (e.g., as described herein), a composition of any of the preceding composition aspects and embodiments (e.g., as described herein), a nucleic acid of any of the preceding nucleic acid aspects and embodiments (e.g., as described herein), a vector of any of the preceding vector aspects and embodiments (e.g., as described herein), a cell (or population of cells) of any of the preceding cell aspects and embodiments (e.g., as described herein), or a gene editing system of any of the preceding gene editing system aspects and embodiments (e.g., as described herein), for use in the treatment of a disease.

In an aspect, the disclosure provides a gRNA molecule of any of the preceding gRNA aspects and embodiments (e.g., as described herein), a composition of any of the preceding composition aspects and embodiments (e.g., as described herein), a nucleic acid of any of the preceding nucleic acid aspects and embodiments (e.g., as described herein), a vector of any of the preceding vector aspects and embodiments (e.g., as described herein), a cell (or population of cells) of any of the preceding cell aspects and embodiments (e.g., as described herein), or a gene editing system of any of the preceding gene editing system aspects and embodiments (e.g., as described herein), for use in the treatment of a disease, wherein the disease is a disease associated with expression of a tumor antigen, e.g., a proliferative disease, a precancerous condition, a cancer, and a non-cancer related indication associated with expression of the tumor antigen.

In an aspect, the disclosure provides a gRNA molecule of any of the preceding gRNA aspects and embodiments (e.g., as described herein), a composition of any of the preceding composition aspects and embodiments (e.g., as described herein), a nucleic acid of any of the preceding nucleic acid aspects and embodiments (e.g., as described herein), a vector of any of the preceding vector aspects and embodiments (e.g., as described herein), a cell (or population of cells) of any of the preceding cell aspects and embodiments (e.g., as described herein), or a gene editing system of any of the preceding gene editing system aspects and embodiments (e.g., as described herein), for use in the treatment of a cancer, wherein the cancer is a hematologic cancer selected from the group consisting of chronic lymphocytic leukemia (CLL), acute leukemias, acute lymphoid leukemia (ALL), B-cell acute lymphoid leukemia (B-ALL), T-cell acute lymphoid leukemia (T-ALL), chronic myelogenous leukemia (CML), acute myeloid leukemia (AML), B cell prolymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B cell lymphoma, follicular lymphoma, hairy cell leukemia, small cell- or a large cell-follicular lymphoma, malignant lymphoproliferative conditions, MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndrome, non-Hodgkin's lymphoma, Hodgkin's lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenstrom macroglobulinemia, and pre-leukemia.

In an aspect, the disclosure provides a gRNA molecule of any of the preceding gRNA aspects and embodiments (e.g., as described herein), a composition of any of the preceding composition aspects and embodiments (e.g., as described herein), a nucleic acid of any of the preceding nucleic acid aspects and embodiments (e.g., as described herein), a vector of any of the preceding vector aspects and embodiments (e.g., as described herein), a cell (or population of cells) of any of the preceding cell aspects and embodiments (e.g., as described herein), or a gene editing system of any of the preceding gene editing system aspects and embodiments (e.g., as described herein), for use in the treatment of a cancer, e.g., wherein the cancer is selected from the group consisting of mesothelioma, adenocarcinoma, glioblastoma, colon cancer, rectal cancer, renal-cell carcinoma, liver cancer, non-small cell carcinoma of the lung, cancer of the small intestine, cancer of the esophagus, melanoma, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, non-Hodgkin's lymphoma, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, solid tumors of childhood, cancer of the bladder, cancer of the kidney or ureter, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain stem glioma, pituitary adenoma, Kaposi's sarcoma, epidermoid cancer, squamous cell cancer, T-cell lymphoma, environmentally induced cancers, combinations of said cancers, and metastatic lesions of said cancers.

›BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 : Editing efficiency at targeted B2M locus in CD34+ hematopoietic stem cells by different Cas9 variants, as evaluated by NGS and Flow cytometry. NLS=SV40 NLS; His6 (SEQ ID NO: 108) or His8 (SEQ ID NO: 109) refers to 6 or 8 histidine residues, respectively; TEV=tobacco etch virus cleavage site; Cas9=wild type S. pyogenes Cas9-mutations or variants are as indicated).

FIG. 2 : Editing efficiency at targeted B2M locus in primary human T cells by different Cas9 variants and a range of concentrations, as measured by flow cytometry.

FIG. 3 : Editing efficiency of two different Cas9 variants, at various concentrations, in primary human T cells using two different gRNAs targeting either B2M (left panel) or TRAC (right panel). Editing efficiency (% editing) was measured by flow cytometry by measuring the loss of cell surface expression of B2M (left panel) or TCR (right panel).

FIG. 4 : Schematic for gRNA design targeting intron 9-10 (the intron between exon 9 and exon 10) of hTET2.

FIG. 5 : Schematic for AAV targeting construct (not drawn to scale).

FIG. 6 : FACS staining shows that 11.4% of CD3+ cells were BCMA10_CAR+ using g1-RNA and 13.5% using g45-RNA at day 7. The percentage of BCMA10_CAR+ cells increased over time.

FIG. 7 : FACS staining shows CD3+ cells that were BCMA10_CAR+ using g45 and a different donor than used in FIG. 6 . The percentage of BCMA10_CAR+ cells increased over time.

FIG. 8 : The total cell fold change is shown for RNP-AAV treated, RNP treated, and debeaded only groups. The expansion of BCMA-CAR+ cells from day 7 to day 10 was slightly faster than the total population (4.3 vs 2.7 fold)

FIG. 9 : Schematic of PCR primers designed to amplify from outside of the homology region to the BCMA10_CAR insert in order to confirm correct integration at both 5′ and 3′ sites (SEQ ID NOS 10557-10558, 10557-10558, 10559-10560, and 10559-10560, respectively, in order of appearance).

FIG. 10 A and FIG. 10 B : Exemplary guides were evaluated in CD3+ T cells. For each target site, two sets of primers were designed to amplify each locus. The total percent editing, the percent of insertion and the deletion at each target sequence was determined using NGS.

FIG. 11 : An oligo insertion-based assay (see, e.g., Tsai et al., Nature Biotechnology. 33, 187-197; 2015) was used to determine potential off-target genomic sites cleaved by Cas9 targeting TET2. Exemplary gRNAs targeting TET2 and control guides were screened in Cas9-expressing HEK293 cells. High-efficiency editing at the expected target sequences, potential off-targets for some of the guides, and no off-targets for three of the guides were detected.

›DEFINITIONS · 1 of 13

The terms “gene editing system” or “genome editing system” refer to a system of one or more molecules comprising at least a nuclease (or nuclease domain) and a programmable nucleotide binding domain, which necessary and sufficient to direct and effect modification (e.g., single or double-strand break) of nucleic acid at a target sequence by the nuclease (or nuclease domain). In embodiments, the gene editing system is a CRISPR system. In embodiments, the gene editing system is a zinc finger nuclease system (ZFN). In embodiments, the gene editing system is a TALEN system. In embodiments, the gene editing system is a meganuclease system. In embodiments, the gene editing system modifies a site within a TET2 intron. In embodiments, the gene editing system further comprises a template nucleic acid, e.g., a template nucleic acid comprising sequence encoding a chimeric antigen receptor, e.g., as described herein. In embodiments, one or more of the components of the gene editing system may be introduced into cells as nucleic acid encoding said component or components. Without being bound by theory, upon expression of said component or component, the gene editing system is constituted, e.g., in the cell.

The terms “CRISPR system,” “Cas system” or “CRISPR/Cas system” refer to a set of molecules comprising an RNA-guided nuclease or other effector molecule and a guide RNA molecule that together are necessary and sufficient to direct and effect modification of nucleic acid at a target sequence by the RNA-guided nuclease or other effector molecule. In one embodiment, a CRISPR system comprises a guide RNA and a Cas protein, e.g., a Cas9 protein. Such systems comprising a Cas9 or modified Cas9 molecule are referred to herein as “Cas9 systems” or “CRISPR/Cas9 systems.” In one example, the guide RNA molecule and Cas molecule may be complexed, to form a ribonuclear protein (RNP) complex.

The terms “guide RNA,” “guide RNA molecule,” “gRNA molecule” or “gRNA” are used interchangeably, and refer to a set of nucleic acid molecules that promote the specific directing of a RNA-guided nuclease or other effector molecule (typically in complex with the gRNA molecule) to a target sequence. In some embodiments, said directing is accomplished through hybridization of a portion of the gRNA to DNA (e.g., through the gRNA targeting domain), and by binding of a portion of the gRNA molecule to the RNA-guided nuclease or other effector molecule (e.g., through at least the gRNA tracr). In embodiments, a gRNA molecule consists of a single contiguous polynucleotide molecule, referred to herein as a “single guide RNA,” “sgRNA,” or “single-molecule DNA-targeting RNA” and the like. In other embodiments, a gRNA molecule consists of a plurality, usually two, polynucleotide molecules, which are themselves capable of association, usually through hybridization, referred to herein as a “dual guide RNA,” “dgRNA,” or “double-molecule DNA-targeting RNA” and the like. gRNA molecules are described in more detail below, but generally include a targeting domain and a tracr. In embodiments the targeting domain and tracr are disposed on a single polynucleotide. In other embodiments, the targeting domain and tracr are disposed on separate polynucleotides.

The term “targeting domain” as used herein in connection with a gRNA, is the portion of the gRNA molecule that recognizes, e.g., is complementary to, a target sequence, e.g., a target sequence within the nucleic acid of a cell, e.g., within a gene.

The term “crRNA” as used herein in connection with a gRNA molecule, is a portion of the gRNA molecule that comprises a targeting domain and a region that interacts with a tracr to form a flagpole region.

The term “target sequence” refers to a sequence of nucleic acids complementary, for example fully complementary, to a gRNA targeting domain. In embodiments, the target sequence is disposed on genomic DNA. In an embodiment the target sequence is adjacent to (either on the same strand or on the complementary strand of DNA) a protospacer adjacent motif (PAM) sequence recognized by a protein having nuclease or other effector activity, e.g., a PAM sequence recognized by Cas9. The PAM sequence and length may depend on the Cas9 protein used. Non-limiting examples of PAM sequences include 5′-NGG-3′, 5′-NGGNG-3′, 5′-NG-3′, 5′-NAAAAN-3′, 5′-NNAAAAW-3′, 5′-NNNNACA-3′, 5′-GNNNCNNA-3′, and 5′-NNNNGATT-3′ where N represents any nucleotide, and W represents A or T.

In embodiments, the target sequence is a target sequence of an allogeneic T cell target. In embodiments, the target sequence is a target sequence of an inhibitory molecule. In embodiments, the target sequence is a target sequence of a downstream effector of an inhibitory molecule.

The term “flagpole” as used herein in connection with a gRNA molecule, refers to the portion of the gRNA where the crRNA and the tracr bind to, or hybridize to, one another.

The term “tracr” or “tracrRNA” as used herein in connection with a gRNA molecule refers to the portion of the gRNA that binds to a nuclease or other effector molecule. In embodiments, the tracr comprises nucleic acid sequence that binds specifically to Cas9. In embodiments, the tracr comprises nucleic acid sequence that forms part of the flagpole.

The term “Cas” refers to an RNA-guided nuclease of the CRISPR system that together with a guide RNA molecule are necessary and sufficient to direct and effect modification of nucleic acid at a target sequence. One non-limiting example is a Cas molecule from the Type II CRISPR system, e.g., a Cas9 molecule. Another non-limiting example is a Cas molecule is from a Type V CRISPR system, e.g., a Cpf1 molecule.

The terms “Cas9” and “Cas9 molecule” refer to an enzyme from bacterial Type II CRISPR/Cas system responsible for DNA cleavage. In embodiments, Cas9 also includes wild-type protein, mutant protein, variant protein, including non-catalytic protein, and functional fragments thereof. Non-limiting examples of Cas9 sequences are known in the art and provided herein. In some embodiments, Cas9 refers to a Cas9 sequence that comprises at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% homology with; differs at no more than 1%, 2%, 5%, 10%, 15%, 20%, 30%, or 40% of the amino acid residues when compared with; differs by at least 1, 2, 5, 10 or 20 amino acids but by no more than 100, 80, 70, 60, 50, 40 or 30 amino acids from; or is identical to any Cas9 sequence, e.g., wild-type, mutant, variant, non-catalytic, or functional fragment thereof, known in the art or disclosed herein.

›DEFINITIONS · 2 of 13

The terms “Cpf1” and “Cpf1 molecule” refer to an enzyme from a bacterial Type V CRISPR/Cas system responsible for DNA cleavage. In embodiments, Cpf1 also includes wild-type protein, mutant protein, variant protein, including non-catalytic protein, and functional fragments thereof. Non-limiting examples of Cpf1 sequences are known in the art. In some embodiments, Cpf1 refers to a Cpf1 sequence that comprises at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% homology with; differs at no more than 1%, 2%, 5%, 10%, 15%, 20%, 30%, or 40% of the amino acid residues when compared with; differs by at least 1, 2, 5, 10 or 20 amino acids but by no more than 100, 80, 70, 60, 50, 40 or 30 amino acids from; or is identical to any Cpf1 sequence, e.g., wild-type, mutant, variant, non-catalytic, or functional fragment thereof, known in the art.

The term “complementary” as used in connection with nucleic acid, refers to the pairing of bases, A with T or U, and G with C. The term complementary can also refer to nucleic acid molecules that are completely complementary, that is, form A to T or U pairs and G to C pairs across the entire reference sequence, as well as molecules that are at least about 80%, 85%, 90%, 95%, or 99% complementary.

As used herein, “template nucleic acid” refers to a nucleic acid sequence which can be used with a gene editing system, e.g., a CRISPR system, to insert nucleic acid sequence at or near a target sequence e.g., in homology-directed repair or homologous recombination. In embodiments, part of the template nucleic acid sequence is inserted at or near a target sequence. In embodiments, all or substantially all of the template nucleic acid sequence is inserted at or near a target sequence. The template nucleic acid can be single- or double-stranded RNA or DNA. In embodiments, the template nucleic acid is a vector, or is included in a vector, for example an AAV vector, plasmid DNA, minicircle or nanoplasmid. In aspects, the template nucleic acid comprises nucleic acid sequence encoding a chimeric antigen receptor (CAR), e.g., as described herein. In aspects, the template nucleic acid comprises or is included in a vector comprising nucleic acid sequence encoding a chimeric antigen receptor (CAR), e.g., as described herein. In embodiments, the template nucleic acid comprises nucleic acid sequence which is complementary to nucleic acid sequence at or near the target sequence.

An “indel,” as the term is used herein, refers to a nucleic acid comprising one or more insertions of nucleotides, one or more deletions of nucleotides, or a combination of insertions and deletions of nucleotides, relative to an unmodified reference nucleic acid, that results from being exposed to a composition comprising a gRNA molecule, e.g., a CRISPR system. In some embodiments, an indel comprises nucleotides outside of the target sequence. Indels can be determined by sequencing nucleic acid after being exposed to a composition comprising a gRNA molecule, for example, by NGS. With respect to the site of an indel, an indel is said to be “at or near” a reference site (e.g., a site complementary to a targeting domain of a gRNA molecule) if it comprises at least one insertion or deletion within about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 nucleotide(s) of the reference site, or is overlapping with part or all of said reference site (e.g., comprises at least one insertion or deletion overlapping with, or within 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 nucleotides of a site complementary to the targeting domain of a gRNA molecule, e.g., a gRNA molecule described herein). In embodiments, indels are non-naturally occurring, for example, do not correspond to any naturally-occurring genetic mutation (e.g., insertion, deletion or combination thereof), for example, in the target cell.

An “indel pattern,” as the term is used herein, refers to a set of indels that results after exposure to a composition comprising a gene editing system, e.g., a CRISPR system, or gRNA molecule. In an embodiment, the indel pattern comprises or consists of, the top three indels, by frequency of appearance. In an embodiment, the indel pattern comprises or consists of, the top five indels, by frequency of appearance. In an embodiment, the indel pattern comprises or consists of, the indels which are present at greater than about 5% frequency relative to all sequencing reads. In an embodiment, the indel pattern comprises or consists of, the indels which are present at greater than about 10% frequency relative to total number of indel sequencing reads (i.e., those reads that do not consist of the unmodified reference nucleic acid sequence). In an embodiment, the indel pattern includes of any 3 of the top five most frequently observed indels. The indel pattern may be determined, for example, by sequencing cells of a population of cells which were exposed to a gene editing system, e.g., a CRISPR system, e.g., a CRISPR system comprising a gRNA molecule described herein.

An “off-target indel,” as the term I used herein, refers to an indel at or near a site other than the target sequence of the targeting domain of the gRNA molecule. Such sites may comprise, for example, 1, 2, 3, 4, 5 or more mismatch nucleotides relative to the sequence complementary to the targeting domain of the gRNA. In exemplary embodiments, such sites are detected using targeted sequencing of in silico predicted off-target sites, or by an insertional method known in the art.

The term “inhibitory molecule” refers to a molecule, which when activated causes or contributes to an inhibition of cell survival, activation, proliferation and/or function. The term also refers to the gene encoding said molecule and its associated regulatory elements, e.g., promoters, enhancers, etc. In embodiments, an inhibitory molecule is a molecule expressed on an immune effector cell, e.g., on a T cell. Non-limiting examples of inhibitory molecules are PD-1, PD-L1, PD-L2, CTLA4, TIM3, LAG3, CEACAM (e.g., CEACAM-1, CEACAM-3 and/or CEACAM-5), VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, CD80, CD86, B7-H3 (CD276), B7-H4 (VTCN1), HVEM (TNFRSF14 or CD107), KIR, A2aR, MHC class I, MHC class II, GAL9, adenosine, and TGF beta. It will be understood that the term inhibitory molecule may refer to the gene (and its associated regulatory elements) encoding an inhibitory molecule protein when it is used in connection with a target sequence or gRNA molecule. In some embodiments, gene editing systems, e.g., CRISPR systems, comprising one or more gRNA molecules comprising a targeting domain to a sequence of an inhibitory molecule are used in conjunction with the other features disclosed herein (e.g., a CRISPR system to a TET2 intron).

›DEFINITIONS · 3 of 13

The terms “allogeneic T cell target” and “allogeneic T-cell target” are used interchangeably herein, and refer to a protein that mediates or contributes to a host versus graft response, mediates or contributes to a graft versus host response, or is a target for an immunosuppressant; and the gene encoding said molecule and its associated regulatory elements, e.g., promoters. It will be understood that the term allogeneic T cell target may refer to the gene (and its associated regulatory elements) encoding an allogeneic T cell target protein when it is used in connection with a target sequence or gRNA molecule. Without being bound by theory, inhibition or elimination of one or more allogeneic T cell targets, e.g., by use of gene editing systems, e.g., CRISPR systems, to such targets, may improve the efficacy, survival, function and/or viability of, e.g., an allogeneic cell, e.g., an allogeneic T cell, for example, by reducing or eliminating undesirable immunogenicity (such as a host versus graft response or a graft versus host response). An allogeneic T cell target may also refer to a functional fragment, splice variant, or domain of a specified target.

In some embodiments, immunogenicity refers to the initiation of a humoral or cell-mediated immune response. In certain embodiments, undesirable immunogenicity may result from graft versus host disease (GvHD) or graft versus host response, e.g., following an allogeneic transplant, in which the donor/grafted cells or tissues attack the donee/host cells or tissues as foreign. In other embodiments, undesirable immunogenicity may result from host versus graft disease (HvGD), e.g., following an allogeneic transplant, in which the donee/host cells or tissues attack the donor/grafted cells or tissues as foreign.

In a non-limiting example, the protein that mediates or contributes to a graft versus host response or host versus graft response is one or more components of the T cell receptor. In an embodiment, the component of the T cell receptor is the T cell receptor alpha, for example the constant domain of the TCR alpha. In an embodiment, the component of the T cell receptor is the T cell receptor beta chain, for example the constant domain 1 or constant domain 2 of the TCR beta. In an embodiment, the component of the T cell receptor is the T cell receptor delta chain. In an embodiment, the component of the T cell receptor is the T cell receptor epsilon chain. In an embodiment, the component of the T cell receptor is the T cell receptor zeta chain. In an embodiment, the component of the T cell receptor is the T cell receptor gamma chain. Thus, in embodiments where the protein encoded by the allogeneic T cell target is a component of the TCR, the gene encoding the allogeneic T cell target may be, for example, TRAC, TRBC1, TRBC2, CD3D, CD3E, CD3G or CD247, and combinations thereof.

In a non-limiting example, the protein that mediates or contributes to a graft versus host response or host versus graft response is an HLA protein or B2M. Examples of HLA proteins include HLA-A, HLA-B and HLA-C. Thus, in embodiments where the allogeneic T cell target protein is a HLA or B2M protein, the gene encoding the allogeneic T cell target may be, for example, HLA-A, HLA-B, HLA-C or B2M, and combinations thereof. In other embodiments, the allogeneic T cell target protein is NLRC5, and the gene encoding the allogeneic T cell target may be, for example, NLRC5.

In some embodiments, the protein that mediates or contributes to a graft versus host response or a host versus graft response is selected from: HLA-DM, HLA-DO, HLA-DR, HLA-DQ, HLA-DP, CIITA, RFXANK, RFXAP, RFX1, RFX5, NF-YA, NF-YB, NF-YC, X2BP, OCAB, HLA-A, HLA-B, HLA-C, B2M, NLRC5, TRAC, TRBC1, TRBC2, CD247, CD3, CD3D, CD3E, CD3G, DCK, CD52, FKBP1A, and NR3C1. In a non-limiting example, the protein that mediates or contributes to a graft versus host response or host versus graft response is a major histocompatibility complex class II (MHC II) molecule (e.g., HLA-Dx (where x refers to a letter of a MHC II protein, e.g., HLA-DM, HLA-DO, HLA-DR, HLA-DQ and/or HLA-DP)), or a regulatory factor for expression of a MHC II, and combinations thereof. A non-limiting example is CIITA (also referred to herein as C2TA). Thus, in embodiments where the allogeneic T cell target protein is a CIITA, the gene encoding the allogeneic T cell target may be, for example, CIITA. In another non-limiting example, the protein that mediates or contributes to a graft versus host response or host versus graft response is RFXANK. In another non-limiting example, the protein that mediates or contributes to a graft versus host response or host versus graft response is RFXAP. In another non-limiting example, the protein that mediates or contributes to a graft versus host response or host versus graft response is RFX5. In another non-limiting example, the protein that mediates or contributes to a graft versus host response or host versus graft response is RFX1.

In some embodiments, gene editing systems, e.g., CRISPR systems, comprising one or more gRNA molecules comprising a targeting domain to a sequence of an allogenic T cell target are used alone or in conjunction with the other features disclosed herein (e.g., a CRISPR system to a TET2 intron). In embodiments, CRISPR systems targeting TRAC, B2M and/or CIITA are used in conjunction with the other features disclosed herein (e.g., a CRISPR system to a TET2 intron).

The term “target for an immunosuppressant” as used herein refers to a molecular target, for example a receptor or other protein, for an immunosuppressant agent (the terms, “immunosuppressant” and “immunosuppressive” are used interchangeably herein in connection with an agent, or target for an agent). An immunosuppressant agent is an agent that suppresses immune function by one or more mechanisms of action. In other words, an immunosuppressive agent is a role played by a compound which is exhibited by a capability to diminish the extent and/or voracity of an immune response. One example of a type of activity exhibited by an immunosuppressant agent is eliminating T-cells, for example, activated T-cells. Another example of a type of activity exhibited by an immunosuppressant agent is reducing the activity or activation level of T-cells.

›DEFINITIONS · 4 of 13

As a non-limiting example, an immunosuppressive agent can be a calcineurin inhibitor, a target of rapamycin, an interleukin-2 a-chain blocker, an inhibitor of inosine monophosphate dehydrogenase, an inhibitor of dihydrofolic acid reductase, a corticosteroid, cyclosporine, or an immunosuppressive antimetabolite. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-cells or by inhibiting the activation of helper cells. As non-limiting examples, targets for immunosuppressive agent can be a receptor for an immunosuppressive agent such as: deoxycytidine kinase, CD52, glucocorticoid receptor (GR), a FKBP family gene member, e.g., FKBP12, and a cyclophilin family gene member. In an embodiment, the target for an immunosuppressant is deoxycytidine kinase (DCK), and the immunosuppressant is a nucleoside analog-based drug such as cytarabine (cytosine arabinoside) or gemcitabine. In an embodiment, the target for an immunosuppressant is GR, and the immunosuppressant is a corticosteroid such as dexamethasone. In an embodiment, the target for an immunosuppressant is CD52, and the immunosuppressant is an anti-CD52 antibody or antigen-binding fragment thereof such as alemtuzumab (CAMPATH®). In an embodiment, the target for an immunosuppressant is FKBP12, and the immunosuppressant is FK506 (or analog or FKBP12-binding fragment thereof), cyclosporine, rapamycin or rapalog, or mTor inhibitor such as RAD001. Thus, in embodiments where the allogeneic T cell target is a target for an immunosuppressant protein, the gene encoding the allogeneic T cell target may be, for example, NR3C1, FKBP1A, CD52, or DCK, and combinations thereof. In some embodiments, gene editing systems, e.g., CRISPR systems, comprising one or more gRNA molecules comprising a targeting domain to a sequence of allogenic T cell target are used in conjunction with the other features disclosed herein (e.g., a CRISPR system to a TET2 intron). In embodiments, CRISPR systems targeting TRAC and FKBP1A are used in conjunction with the other features disclosed herein (e.g., a CRISPR system to a TET2 intron).

“Tet” as the term is used herein, refers to the family of genes, and the proteins encoded by said genes, of the ten-eleven translocation methlcytosine dioxygenase family. Tet includes, for example, Tet1, Tet2 and Tet3.

“Tet2” as the term is used herein, refers to gene, tet methylcytosine dioxygenase 2, and the protein encoded by said gene, the tet2 methylcytosine dioxygenase, which catalyzes the conversion of methylcytosine to 5-hydroxymethylcytosine. It is sometimes also referred to as “KIAA1546,” “FLJ20032” and “tet oncogene family member 2.” The encoded protein is involved in myelopoiesis, and defects in this gene have been associated with several myeloproliferative disorders. In the human genome, TET2 is located on chromosome 4q24. The Tet2 gene includes both the introns and exons of the associated gene. Currently six TET2 isoforms have been described and their Genebank numbers are: NM_001127208.2; XM_005263082.1; XM_006714242.2; NM_017628.4; XM_011532044.1; and XM_011532043.1.

An example of the protein sequence of human Tet2 is provided as UniProt accession number Q6N021:

The tet2 gene is located on chromosome 4, location GRCh38.p2 (GCF_000001405.28) (NC_000004.12 (105145875 to 105279803); Gene ID 54790.

Examples of nucleic acid sequences encoding Tet2 are provided below. There are 6 identified isoforms of human Tet2 have been identified. The mRNA sequences are provided below (In embodiments, in each sequence, T may be replaced with U). In embodiments, Tet2 includes the proteins encoded by each of the sequences below:

The term “gene” or “gene sequence” is meant to refer to a genetic sequence, e.g., a nucleic acid sequence. The term “gene” is intended to encompass a complete gene sequence or a partial gene sequence. The term “gene” refers to a sequence that encodes a protein or polypeptide or a sequence that does not encode a protein or polypeptide, e.g., a regulatory sequence, leader sequence, signal sequence, intron, or other non-protein coding sequence. The term “intron” refers to nucleic acid sequence within a gene which is noncoding for the protein expressed from said gene. Intronic sequence may be transcribed from DNA into RNA, but may be removed before the protein is expressed.

The term “exon” refers to nucleic acid sequence within a gene which encodes a protein expressed from said gene.

The term “intron-exon junction,” when used in connection with a gene editing system or gRNA molecule, refers to a sequence which includes nucleotides of an exon and nucleotides of an intron. In exemplary embodiments, an intron-exon junction is a gRNA target sequence, whereby, when recognized by a CRISPR system comprising a gRNA comprising a targeting domain complementary to the intron-exon junction target sequence, said CRISPR system modifies, e.g., produces a break, at or near the target sequence between two nucleotides of an intron. In other exemplary embodiments, an intron-exon junction is a gRNA target sequence, whereby, when recognized by a CRISPR system comprising a gRNA comprising a targeting domain complementary to the intron-exon junction target sequence, said CRISPR system modifies, e.g., produces a break, at or near the target sequence between two nucleotides of an exon. In other exemplary embodiments, an intron-exon junction is a gRNA target sequence, whereby, when recognized by a CRISPR system comprising a gRNA comprising a targeting domain complementary to the intron-exon junction target sequence, said CRISPR system modifies, e.g., produces a break, at or near the target sequence between a nucleotide of an exon and a nucleotide of an intron.

The term “a,” “an,” or “the” refers to one or to more than one of the grammatical object of the article. The term may mean “one,” “one or more,” “at least one,” or “one or more than one.” By way of example, “an element” means one element or more than one element. The term “or” means “and/or” unless otherwise stated. The term “including” or “containing” is not limiting.

›DEFINITIONS · 5 of 13

The term “about” when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of +20% or in some instances +10%, or in some instances +5%, or in some instances +1%, or in some instances +0.1% from the specified value, as such variations are appropriate to perform the disclosed methods.

The term “Chimeric Antigen Receptor” or alternatively a “CAR” refers to a set of polypeptides, typically two in the simplest embodiments, which when in an immune effector cell, provides the cell with specificity for a target cell, typically a cancer cell, and with intracellular signal generation. In some embodiments, a CAR comprises at least an extracellular antigen binding domain, a transmembrane domain and a cytoplasmic signaling domain (also referred to herein as “an intracellular signaling domain”) comprising a functional signaling domain derived from a stimulatory molecule and/or costimulatory molecule as defined below. In some aspects, the set of polypeptides are contiguous with each other. In some embodiments, the set of polypeptides include a dimerization switch that, upon the presence of a dimerization molecule, can couple the polypeptides to one another, e.g., can couple an antigen binding domain to an intracellular signaling domain. In one aspect, the stimulatory molecule is the zeta chain associated with the T cell receptor complex. In one aspect, the cytoplasmic signaling domain further comprises one or more functional signaling domains derived from at least one costimulatory molecule as defined below. In one aspect, the costimulatory molecule is chosen from the costimulatory molecules described herein, e.g., 41BB (i.e., CD137), CD27 and/or CD28. In one aspect, the CAR comprises a chimeric fusion protein comprising an extracellular antigen binding domain, a transmembrane domain and an intracellular signaling domain comprising a functional signaling domain derived from a stimulatory molecule. In one aspect, the CAR comprises a chimeric fusion protein comprising an extracellular antigen binding domain, a transmembrane domain and an intracellular signaling domain comprising a functional signaling domain derived from a costimulatory molecule and a functional signaling domain derived from a stimulatory molecule. In one aspect, the CAR comprises a chimeric fusion protein comprising an extracellular antigen binding domain, a transmembrane domain and an intracellular signaling domain comprising two functional signaling domains derived from one or more costimulatory molecule(s) and a functional signaling domain derived from a stimulatory molecule. In one aspect, the CAR comprises a chimeric fusion protein comprising an extracellular antigen binding domain, a transmembrane domain and an intracellular signaling domain comprising at least two functional signaling domains derived from one or more costimulatory molecule(s) and a functional signaling domain derived from a stimulatory molecule. In one aspect the CAR comprises an optional leader sequence at the amino-terminus (N-ter) of the CAR fusion protein. In one aspect, the CAR further comprises a leader sequence at the N-terminus of the extracellular antigen binding domain, wherein the leader sequence is optionally cleaved from the antigen binding domain (e.g., a scFv) during cellular processing and localization of the CAR to the cellular membrane.

A CAR that comprises an antigen binding domain (e.g., a scFv, or TCR) that targets a specific tumor marker X, such as those described herein, is also referred to as XCAR. For example, a CAR that comprises an antigen binding domain that targets CD19 is referred to as CD19CAR. As another example, a CAR that comprises an antigen binding domain that targets BCMA is referred to as a BCMA CAR.

The term “signaling domain” refers to the functional portion derived from protein which acts by transmitting information within a cell to regulate cellular activity via defined signaling pathways, for example, by generating second messengers or functioning as effectors by responding to such messengers. In embodiments, a signaling domain refers to a variant or homolog, e.g., a functional variant or homolog, of a naturally occurring signaling domain, for example a signaling domain variant having at least about 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to a naturally-occurring signaling domain.

The term “antibody,” as used herein, refers to one or more proteins or polypeptide sequence derived from an immunoglobulin molecule which specifically binds an antigen. Antibodies can be polyclonal or monoclonal, multiple or single chain, functional fragments (e.g., Fab fragments or scFv), or intact immunoglobulins, and may be derived from natural sources or from recombinant sources. Antibodies can be, e.g., dimers or tetramers of immunoglobulin molecules. Antibodies can be from any species or chimeric, including human or humanized antibodies.

The term “antibody fragment” refers to at least one portion of an antibody, that retains the ability to specifically interact with (e.g., by binding, steric hindrance, stabilizing/destabilizing, spatial distribution) an epitope of an antigen. In some embodiments, the antibody fragment retains an affinity for the epitope of an antigen broadly comparable to that of the intact immunoglobulin. For example, the antibody fragment may retain 80%, 85%, 90%, 95%, 99%, or more of the affinity seen with the intact immunoglobulin, as measured, e.g., by ELISA, Biacore, or other suitable assays. Examples of antibody fragments include, but are not limited to, Fab, Fab′, F(ab′)2, Fv fragments, scFv antibody fragments, disulfide-linked Fvs (sdFv), a Fd fragment consisting of the VH and CH1 domains, linear antibodies, single domain antibodies such as sdAb (either VL or VH), camelid VHH domains, multi-specific antibodies formed from antibody fragments such as a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region, and an isolated CDR or other epitope binding fragments of an antibody. An antigen binding fragment can also be incorporated into single domain antibodies, maxibodies, minibodies, nanobodies, intrabodies, diabodies, triabodies, tetrabodies, v-NAR and bis-scFv (see, e.g., Hollinger and Hudson, Nature Biotechnology 23:1126-1136, 2005). Antigen binding fragments can also be grafted into scaffolds based on polypeptides such as a fibronectin type III (Fn3) (see U.S. Pat. No. 6,703,199, which describes fibronectin polypeptide minibodies).

›DEFINITIONS · 6 of 13

The term “scFv” refers to a fusion protein comprising at least one antibody fragment comprising a variable region of a light chain and at least one antibody fragment comprising a variable region of a heavy chain, wherein the light and heavy chain variable regions are contiguously linked, e.g., directly or via a synthetic linker, e.g., a short flexible polypeptide linker, and capable of being expressed as a single chain polypeptide, and wherein the scFv retains the specificity of the intact antibody from which it is derived. Unless specified, as used herein an scFv may have the VL and VH variable regions in either order, e.g., with respect to the N-terminal and C-terminal ends of the polypeptide, the scFv may comprise VL-linker-VH or may comprise VH-linker-VL.

The portion of the CAR comprising an antibody or antibody fragment thereof may exist in a variety of forms where the antigen binding domain is expressed as part of a contiguous polypeptide chain including, for example, a single domain antibody fragment (sdAb), a single chain antibody (scFv), a humanized antibody or bispecific antibody (Harlow et al., 1999, In: Using Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, NY; Harlow et al., 1989, In: Antibodies: A Laboratory Manual, Cold Spring Harbor, New York; Houston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879-5883; Bird et al., 1988, Science 242:423-426). In one aspect, the antigen binding domain of a CAR composition comprises an antibody fragment. In a further aspect, the CAR comprises an antibody fragment that comprises a scFv. In another aspect, the CAR comprises a full antibody including the Fc region.

The portion of the CAR comprising a full antibody may be of any type (e.g., IgG, IgE, IgM, IgD, IgA and IgY), any class (e.g., IgG 1, IgG2, IgG 3, IgG4, IgA1 and IgA2) or any subclass. In some embodiments the Fc region is an IgG type constant region. In certain embodiments the Fc region of the full antibody includes an Fc region from IgG1, IgG2, IgG3, IgG4, IgA, IgA1, IgA2, IgM, IgE, IgD, and IgY, or a fragment thereof. In some embodiments the Fc region is an IgG1. The Fc region may be a native sequence Fc region, or a variant Fc region. In one embodiment, the Fc region is a human Fc region.

The portion of the CAR comprising an antibody or antibody fragment thereof may comprise the CDR sequences of an antibody coupled with human or other antibody framework sequences. The framework sequences may be the same or different from those in a starting antibody. The precise amino acid sequence boundaries of a given CDR can be determined using any of a number of well-known schemes, including those described by Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (“Kabat” numbering scheme), A1-Lazikani et al., (1997) JMB 273,927-948 (“Chothia” numbering scheme), or a combination thereof. As used herein, the term “binding domain” or “antibody molecule” refers to a protein, e.g., an immunoglobulin chain or fragment thereof, comprising at least one immunoglobulin variable domain sequence. The term “binding domain” or “antibody molecule” encompasses antibodies and antibody fragments, as well as multispecific binding constructs. In an embodiment, an antibody molecule is a multispecific antibody molecule, e.g., it comprises a plurality of immunoglobulin variable domain sequences forming antigen-binding sites for different epitopes of antigens, when a first immunoglobulin variable domain sequence of the plurality has binding specificity for a first epitope and at least a second immunoglobulin variable domain sequence of the plurality has binding specificity for a second epitope. In an embodiment, a multispecific antibody molecule is a bispecific antibody molecule. A bispecific antibody has specificity for no more than two antigens. A bispecific antibody molecule is characterized by a first immunoglobulin variable domain sequence which has binding specificity for a first epitope and a second immunoglobulin variable domain sequence that has binding specificity for a second epitope. In other embodiments, a “binding domain” or “antibody molecule” encompasses multivalent antibody molecules, e.g., it comprises a plurality of immunoglobulin variable domain sequences forming two or more antigen binding sites for the same epitope of an antigen.

The term “antibody heavy chain,” refers to the larger of the two types of polypeptide chains present in antibody molecules in their naturally occurring conformations, and which normally determines the class to which the antibody belongs.

The term “antibody light chain,” refers to the smaller of the two types of polypeptide chains present in antibody molecules in their naturally occurring conformations. Kappa (K) and lambda (k) light chains refer to the two major antibody light chain isotypes.

The term “recombinant antibody” refers to an antibody which is generated using recombinant DNA technology, such as, for example, an antibody expressed by a bacteriophage or yeast expression system or in any other host cell. The term also includes an antibody which has been generated by the synthesis of a DNA molecule encoding the antibody and which DNA molecule expresses an antibody protein, or an amino acid sequence specifying the antibody, wherein the DNA or amino acid sequence has been obtained using recombinant DNA or amino acid sequence technology which is available and well known in the art.

The term “antigen” or “Ag” refers to a molecule that provokes an immune response. This immune response may involve either antibody production, or the activation of specific immunologically-competent cells, or both. The term also refers to any peptide bound by an antibody or antibody fragment thereof. The skilled artisan will understand that any macromolecule, including virtually all proteins or peptides, can serve as an antigen. Furthermore, antigens can be derived from recombinant or genomic DNA. A skilled artisan will understand that any DNA, which comprises a nucleotide sequences or a partial nucleotide sequence encoding a protein that elicits an immune response therefore encodes an “antigen” as that term is used herein. Furthermore, one skilled in the art will understand that an antigen need not be encoded solely by a full length nucleotide sequence of a gene. It is readily apparent that the present disclosure includes, but is not limited to, the use of partial nucleotide sequences of more than one gene and that these nucleotide sequences are arranged in various combinations to encode polypeptides that elicit the desired immune response. Moreover, a skilled artisan will understand that an antigen need not be encoded by a “gene” at all. It is readily apparent that an antigen can be generated synthesized or can be derived from a biological sample, or might be macromolecule besides a polypeptide. Such a biological sample can include, but is not limited to a tissue sample, a tumor sample, a cell or a fluid with other biological components.

›DEFINITIONS · 7 of 13

The term “anti-cancer effect” refers to a biological effect which can be manifested by various means, including but not limited to, e.g., a decrease in tumor volume, a decrease in the number of cancer cells, a decrease in the number of metastases, an increase in life expectancy, decrease in cancer cell proliferation, decrease in cancer cell survival, or amelioration of various physiological symptoms associated with the cancerous condition. An “anti-cancer effect” can also be manifested by the ability of the peptides, polynucleotides, cells and antibodies in prevention of the occurrence of cancer in the first place. The term “anti-tumor effect” refers to a biological effect which can be manifested by various means, including but not limited to, e.g., a decrease in tumor volume, a decrease in the number of tumor cells, a decrease in tumor cell proliferation, or a decrease in tumor cell survival.

The term “autologous” refers to any material derived from the same individual into whom it is introduced.

The term “allogeneic” refers to any material derived from a different animal of the same species as the individual to whom the material is introduced. Two or more individuals are said to be allogeneic to one another when the genes at one or more loci are not identical. In some aspects, allogeneic material from individuals of the same species may be sufficiently unlike genetically to interact antigenically

The term “xenogeneic” refers to a graft derived from an animal of a different species.

The term “cancer” refers to a disease characterized by the uncontrolled growth of aberrant cells. Cancer cells can spread locally or through the bloodstream and lymphatic system to other parts of the body. Examples of various cancers are described herein and include but are not limited to, breast cancer, prostate cancer, ovarian cancer, cervical cancer, skin cancer, pancreatic cancer, colorectal cancer, renal cancer, liver cancer, brain cancer, lymphoma, leukemia, lung cancer and the like. The terms “tumor” and “cancer” are used interchangeably herein, e.g., both terms encompass solid and liquid, e.g., diffuse or circulating, tumors. As used herein, the term “cancer” or “tumor” includes premalignant, as well as malignant cancers and tumors.

“Derived from” as that term is used herein, indicates a relationship between a first and a second molecule. It generally refers to structural similarity between the first molecule and a second molecule and does not connote or include a process or source limitation on a first molecule that is derived from a second molecule. For example, in the case of an intracellular signaling domain that is derived from a CD3zeta molecule, the intracellular signaling domain retains sufficient CD3zeta structure such that is has the required function, namely, the ability to generate a signal under the appropriate conditions. It does not connote or include a limitation to a particular process of producing the intracellular signaling domain, e.g., it does not mean that, to provide the intracellular signaling domain, one must start with a CD3zeta sequence and delete unwanted sequence, or impose mutations, to arrive at the intracellular signaling domain.

The phrase “disease associated with expression of a tumor antigen as described herein” includes, but is not limited to, a disease associated with expression of a tumor antigen as described herein or condition associated with cells which express a tumor antigen as described herein including, e.g., proliferative diseases such as a cancer or malignancy or a precancerous condition such as a myelodysplasia, a myelodysplastic syndrome or a preleukemia; or a noncancer-related indication associated with cells which express a tumor antigen as described herein. In one aspect, a cancer associated with expression of a tumor antigen as described herein is a hematological cancer. In one aspect, a cancer associated with expression of a tumor antigen as described herein is a solid cancer. Further diseases associated with expression of a tumor antigen described herein include, but not limited to, e.g., atypical and/or non-classical cancers, malignancies, precancerous conditions or proliferative diseases associated with expression of a tumor antigen as described herein. Non-cancer related indications associated with expression of a tumor antigen as described herein include, but are not limited to, e.g., autoimmune disease, (e.g., lupus), inflammatory disorders (allergy and asthma) and transplantation. In some embodiments, the tumor antigen-expressing cells express, or at any time expressed, mRNA encoding the tumor antigen. In an embodiment, the tumor antigen-expressing cells produce the tumor antigen protein (e.g., wild-type or mutant), and the tumor antigen protein may be present at normal levels or reduced levels. In an embodiment, the tumor antigen-expressing cells produced detectable levels of a tumor antigen protein at one point, and subsequently produced substantially no detectable tumor antigen protein.

The term “conservative sequence modifications” refers to amino acid modifications that do not significantly affect or alter the binding characteristics of the antibody or antibody fragment containing the amino acid sequence. Such conservative modifications include amino acid substitutions, additions and deletions. Modifications can be introduced into an antibody or antibody fragment described herein by standard techniques known in the art, such as site-directed mutagenesis and PCR-mediated mutagenesis. Conservative amino acid substitutions are ones in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, tryptophan), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, one or more amino acid residues within a CAR of the disclosure can be replaced with other amino acid residues from the same side chain family and the altered CAR can be tested using the functional assays described herein.

›DEFINITIONS · 8 of 13

The term “stimulation,” refers to a primary response induced by binding of a stimulatory molecule (e.g., a TCR/CD3 complex or CAR) with its cognate ligand (or tumor antigen in the case of a CAR) thereby mediating a signal transduction event, such as, but not limited to, signal transduction via the TCR/CD3 complex or signal transduction via the appropriate NK receptor or signaling domains of the CAR. Stimulation can mediate altered expression of certain molecules.

The term “stimulatory molecule,” refers to a molecule expressed by an immune cell (e.g., T cell, NK cell, B cell) that provides the cytoplasmic signaling sequence(s) that regulate activation of the immune cell in a stimulatory way for at least some aspect of the immune cell signaling pathway. In one aspect, the signal is a primary signal that is initiated by, for instance, binding of a TCR/CD3 complex with an MHC molecule loaded with peptide, and which leads to mediation of a T cell response, including, but not limited to, proliferation, activation, differentiation, and the like. A primary cytoplasmic signaling sequence (also referred to as a “primary signaling domain”) that acts in a stimulatory manner may contain a signaling motif which is known as immunoreceptor tyrosine-based activation motif or ITAM. Examples of an ITAM containing cytoplasmic signaling sequence that is of particular use includes, but is not limited to, those derived from CD3 zeta, common FcR gamma (FCERIG), Fc gamma RIIa, FcR beta (Fc Epsilon R1b), CD3 gamma, CD3 delta, CD3 epsilon, CD79a, CD79b, DAP10, and DAP12. In a specific CAR embodiment, the intracellular signaling domain in any one or more CARS of the disclosure comprises an intracellular signaling sequence, e.g., a primary signaling sequence of CD3-zeta. In a specific CAR of the disclosure, the primary signaling sequence of CD3-zeta is the sequence provided as SEQ ID NO:21, or the equivalent residues from a non-human species, e.g., mouse, rodent, monkey, ape and the like. In a specific CAR of the disclosure, the primary signaling sequence of CD3-zeta is the sequence as provided in SEQ ID NO: 24, or the equivalent residues from a non-human species, e.g., mouse, rodent, monkey, ape and the like.

The term “antigen presenting cell” or “APC” refers to an immune system cell such as an accessory cell (e.g., a B-cell, a dendritic cell, and the like) that displays a foreign antigen complexed with major histocompatibility complexes (MHC's) on its surface. T-cells may recognize these complexes using their T-cell receptors (TCRs). APCs process antigens and present them to T-cells.

An “intracellular signaling domain,” as the term is used herein, refers to an intracellular portion derived from a molecule, e.g., a stimulatory or costimulatory molecule. The intracellular signaling domain generates a signal that promotes an immune effector function of the CAR containing cell, e.g., a CART cell. Examples of immune effector function, e.g., in a CART cell, include cytolytic activity and helper activity, including the secretion of cytokines.

In an embodiment, the intracellular signaling domain can comprise a primary intracellular signaling domain. Exemplary primary intracellular signaling domains include those derived from the molecules responsible for primary stimulation, or antigen dependent simulation. In an embodiment, the intracellular signaling domain can comprise a costimulatory intracellular domain. Exemplary costimulatory intracellular signaling domains include those derived from molecules responsible for costimulatory signals, or antigen independent stimulation. For example, in the case of a CART, a primary intracellular signaling domain can comprise a cytoplasmic sequence of a T cell receptor, and a costimulatory intracellular signaling domain can comprise cytoplasmic sequence from co-receptor or costimulatory molecule.

A primary intracellular signaling domain can comprise a signaling motif which is known as an immunoreceptor tyrosine-based activation motif or ITAM. Examples of ITAM containing primary cytoplasmic signaling sequences include, but are not limited to, those derived from CD3 zeta, common FcR gamma (FCER1G), Fc gamma RIIa, FcR beta (Fc Epsilon R1b), CD3 gamma, CD3 delta, CD3 epsilon, CD79a, CD79b, DAP10, and DAP12.

The term “zeta” or alternatively “zeta chain”, “CD3-zeta” or “TCR-zeta” is defined as the protein provided as GenBan Acc. No. BAG36664.1, or the equivalent residues from a non-human species, e.g., mouse, rodent, monkey, ape and the like, and a “zeta stimulatory domain” or alternatively a “CD3-zeta stimulatory domain” or a “TCR-zeta stimulatory domain” is defined as the amino acid residues from the cytoplasmic domain of the zeta chain, or functional derivatives thereof, that are sufficient to functionally transmit an initial signal necessary for T cell activation. In one aspect the cytoplasmic domain of zeta comprises residues 52 through 164 of GenBank Acc. No. BAG36664.1 or the equivalent residues from a non-human species, e.g., mouse, rodent, monkey, ape and the like, that are functional orthologs thereof. In one aspect, the “zeta stimulatory domain” or a “CD3-zeta stimulatory domain” is the sequence provided as SEQ ID NO: 21. In one aspect, the “zeta stimulatory domain” or a “CD3-zeta stimulatory domain” is the sequence provided as SEQ ID NO: 24.

The term “costimulatory molecule” refers to a cognate binding partner on a T cell that specifically binds with a costimulatory ligand, thereby mediating a costimulatory response by the T cell, such as, but not limited to, proliferation. Costimulatory molecules are cell surface molecules other than antigen receptors or their ligands that are contribute to an efficient immune response. Costimulatory molecules include, but are not limited to an MHC class I molecule, BTLA and a Toll ligand receptor, as well as OX40, CD27, CD28, CDS, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), and 4-1BB (CD137). Further examples of such costimulatory molecules include CDS, ICAM-1, GITR, BAFFR, HVEM (LIGHTR), SLAMF7, NKp80 (KLRF1), NKp44, NKp30, NKp46, CD160, CD19, CD4, CD8alpha, CD8beta, IL2R beta, IL2R gamma, IL7R alpha, ITGA4, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CD11d, ITGAE, CD103, ITGAL, CD11a, LFA-1, ITGAM, CD11b, ITGAX, CD11c, ITGB1, CD29, ITGB2, CD18, LFA-1, ITGB7, NKG2D, NKG2C, TNFR2, TRANCE/RANKL, DNAM1 (CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (Tactile), CEACAM1, CRTAM, Ly9 (CD229), CD160 (BY55), PSGL1, CD100 (SEMA4D), CD69, SLAMF6 (NTB-A, Lyl08), SLAM (SLAMFi, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, LAT, GADS, SLP-76, PAG/Cbp, CD19a, and a ligand that specifically binds with CD83.

›DEFINITIONS · 9 of 13

A costimulatory intracellular signaling domain can be the intracellular portion of a costimulatory molecule. A costimulatory molecule can be represented in the following protein families: TNF receptor proteins, Immunoglobulin-like proteins, cytokine receptors, integrins, signaling lymphocytic activation molecules (SLAM proteins), and activating NK cell receptors. Examples of such molecules include CD27, CD28, 4-1BB (CD137), OX40, GITR, CD30, CD40, ICOS, BAFFR, HVEM, ICAM-1, lymphocyte function-associated antigen-1 (LFA-1), CD2, CDS, CD7, CD287, LIGHT, NKG2C, NKG2D, SLAMF7, NKp80, NKp30, NKp44, NKp46, CD160, B7-H3, and a ligand that specifically binds with CD83, and the like.

The intracellular signaling domain can comprise the entire intracellular portion, or the entire native intracellular signaling domain, of the molecule from which it is derived, or a functional fragment or derivative thereof.

The term “4-1BB” refers to a member of the TNFR superfamily with an amino acid sequence provided as GenBank Acc. No. AAA62478.2, or the equivalent residues from a non-human species, e.g., mouse, rodent, monkey, ape and the like; and a “4-1BB costimulatory domain” is defined as amino acid residues 214-255 of GenBank Acc. No. AAA62478.2, or the equivalent residues from a non-human species, e.g., mouse, rodent, monkey, ape and the like. In one aspect, the “4-1BB costimulatory domain” is the sequence provided as SEQ ID NO: 16 or the equivalent residues from a non-human species, e.g., mouse, rodent, monkey, ape and the like.

“Immune effector cell,” as that term is used herein, refers to a cell that is involved in an immune response, e.g., in the promotion of an immune effector response. Examples of immune effector cells include T cells, e.g., alpha/beta T cells and gamma/delta T cells, B cells, natural killer (NK) cells, natural killer T (NKT) cells, mast cells, and myeloic-derived phagocytes.

“Immune effector function or immune effector response,” as that term is used herein, refers to function or response, e.g., of an immune effector cell, that enhances or promotes an immune attack of a target cell. E.g., an immune effector function or response refers a property of a T or NK cell that promotes killing or the inhibition of growth or proliferation, of a target cell. In the case of a T cell, primary stimulation and co-stimulation are examples of immune effector function or response.

The term “encoding” refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (e.g., rRNA, tRNA and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom. Thus, a gene, cDNA, or RNA, encodes a protein if transcription and translation of mRNA corresponding to that gene produces the protein in a cell or other biological system. Both the coding strand, the nucleotide sequence of which is identical to the mRNA sequence and is usually provided in sequence listings, and the non-coding strand, used as the template for transcription of a gene or cDNA, can be referred to as encoding the protein or other product of that gene or cDNA.

Unless otherwise specified, a “nucleotide sequence encoding an amino acid sequence” includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. The phrase nucleotide sequence that encodes a protein or an RNA may also include introns to the extent that the nucleotide sequence encoding the protein may in some version contain an intron(s).

The term “effective amount” or “therapeutically effective amount” are used interchangeably herein, and refer to an amount of a compound, formulation, material, or composition, as described herein effective to achieve a particular biological result.

The term “endogenous” refers to any material from or produced inside an organism, cell, tissue or system.

The term “exogenous” refers to any material introduced from or produced outside an organism, cell, tissue or system.

The term “expression” refers to the transcription and/or translation of a particular nucleotide sequence driven by a promoter.

The term “transfer vector” refers to a composition of matter which comprises an isolated nucleic acid and which can be used to deliver the isolated nucleic acid to the interior of a cell. Numerous vectors are known in the art including, but not limited to, linear polynucleotides, polynucleotides associated with ionic or amphiphilic compounds, plasmids, and viruses. Thus, the term “transfer vector” includes an autonomously replicating plasmid or a virus. The term should also be construed to further include non-plasmid and non-viral compounds which facilitate transfer of nucleic acid into cells, such as, for example, a polylysine compound, liposome, and the like. Examples of viral transfer vectors include, but are not limited to, adenoviral vectors, adeno-associated virus vectors, retroviral vectors, lentiviral vectors, and the like.

The term “expression vector” refers to a vector comprising a recombinant polynucleotide comprising expression control sequences operatively linked to a nucleotide sequence to be expressed. An expression vector comprises sufficient cis-acting elements for expression; other elements for expression can be supplied by the host cell or in an in vitro expression system. Expression vectors include all those known in the art, including cosmids, plasmids (e.g., naked or contained in liposomes) and viruses (e.g., lentiviruses, retroviruses, adenoviruses, and adeno-associated viruses) that incorporate the recombinant polynucleotide.

The term “homologous” or “identity” refers to the subunit sequence identity between two polymeric molecules, e.g., between two nucleic acid molecules, such as, two DNA molecules or two RNA molecules, or between two polypeptide molecules. When a subunit position in both of the two molecules is occupied by the same monomeric subunit; e.g., if a position in each of two DNA molecules is occupied by adenine, then they are homologous or identical at that position. The homology between two sequences is a direct function of the number of matching or homologous positions; e.g., if half (e.g., five positions in a polymer ten subunits in length) of the positions in two sequences are homologous, the two sequences are 50% homologous; if 90% of the positions (e.g., 9 of 10), are matched or homologous, the two sequences are 90% homologous.

›DEFINITIONS · 10 of 13

“Humanized” forms of non-human (e.g., murine) antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab′, F(ab′)2 or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non-human immunoglobulin. For the most part, humanized antibodies and antibody fragments thereof are human immunoglobulins (recipient antibody or antibody fragment) in which one or more, e.g., all six, complementary-determining regions (CDRs) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity, and capacity. In some instances, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, a humanized antibody/antibody fragment can comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences as long as the same antigen specificity is retained. These modifications can further refine and optimize antibody or antibody fragment performance. In general, the humanized antibody or antibody fragment thereof will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or a significant portion of the FR regions are those of a human immunoglobulin sequence. The humanized antibody or antibody fragment can also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For further details, see Jones et al., Nature, 321: 522-525, 1986; Reichmann et al., Nature, 332: 323-329, 1988; Presta, Curr. Op. Struct. Biol., 2: 593-596, 1992.

“Fully human” refers to an immunoglobulin, such as an antibody or antibody fragment, where the whole molecule is of human origin or consists of an amino acid sequence identical to a human form of the antibody or immunoglobulin.

The term “isolated” means altered or removed from the natural state. For example, a nucleic acid or a peptide naturally present in a living animal is not “isolated,” but the same nucleic acid or peptide partially or completely separated from the coexisting materials of its natural state is “isolated.” An isolated nucleic acid or protein can exist in substantially purified form, or can exist in a non-native environment such as, for example, a host cell.

The term “operably linked” or “transcriptional control” refers to functional linkage between a regulatory sequence and a heterologous nucleic acid sequence resulting in expression of the latter. For example, a first nucleic acid sequence is operably linked with a second nucleic acid sequence when the first nucleic acid sequence is placed in a functional relationship with the second nucleic acid sequence. For instance, a promoter is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. The promoter or regulatory sequence may be a cis-acting element or a trans-acting element. Operably linked DNA sequences can be contiguous with each other and, e.g., where necessary to join two protein coding regions, are in the same reading frame.

The term “parenteral” administration of an immunogenic composition includes, e.g., subcutaneous (s.c.), intravenous (i.v.), intramuscular (i.m.), or intrasternal injection, intratumoral, or infusion techniques.

The term “nucleic acid” or “polynucleotide” refers to deoxyribonucleic acids (DNA) or ribonucleic acids (RNA) and polymers thereof in either single- or double-stranded form. Unless specifically limited, the term encompasses nucleic acids containing known analogues of natural nucleotides that have similar binding properties as the reference nucleic acid and are metabolized in a manner similar to naturally occurring nucleotides. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions), alleles, orthologs, SNPs, and complementary sequences as well as the sequence explicitly indicated. Specifically, degenerate codon substitutions may be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed-base and/or deoxyinosine residues (Batzer et al., Nucleic Acid Res. 19:5081 (1991); Ohtsuka et al., J. Biol. Chem. 260:2605-2608 (1985); and Rossolini et al., Mol. Cell. Probes 8:91-98 (1994)).

The terms “peptide,” “polypeptide,” and “protein” are used interchangeably, and refer to a compound comprised of amino acid residues covalently linked by peptide bonds. A protein or peptide must contain at least two amino acids, and no limitation is placed on the maximum number of amino acids that can comprise a protein's or peptide's sequence. Polypeptides include any peptide or protein comprising two or more amino acids joined to each other by peptide bonds. As used herein, the term refers to both short chains, which also commonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and to longer chains, which generally are referred to in the art as proteins, of which there are many types. “Polypeptides” include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, among others. A polypeptide includes a natural peptide, a recombinant peptide, or a combination thereof.

The term “promoter” refers to a DNA sequence recognized by the synthetic machinery of the cell, or introduced synthetic machinery, required to initiate the specific transcription of a polynucleotide sequence.

The term “promoter/regulatory sequence” refers to a nucleic acid sequence which is required for expression of a gene product operably linked to the promoter/regulatory sequence. In some instances, this sequence may be the core promoter sequence and in other instances, this sequence may also include an enhancer sequence and other regulatory elements which are required for expression of the gene product. The promoter/regulatory sequence may, for example, be one which expresses the gene product in a tissue specific manner.

›DEFINITIONS · 11 of 13

A “constitutive” promoter refers to a nucleotide sequence which, when operably linked with a polynucleotide which encodes or specifies a gene product, causes the gene product to be produced in a cell under most or all physiological conditions of the cell.

An “inducible” promoter refers to a nucleotide sequence which, when operably linked with a polynucleotide which encodes or specifies a gene product, causes the gene product to be produced in a cell substantially only when an inducer which corresponds to the promoter is present in the cell.

A “tissue-specific” promoter refers to a nucleotide sequence which, when operably linked with a polynucleotide encodes or specified by a gene, causes the gene product to be produced in a cell substantially only if the cell is a cell of the tissue type corresponding to the promoter.

The terms “cancer associated antigen” or “tumor antigen” interchangeably refers to a molecule (typically a protein, carbohydrate or lipid) that is expressed on the surface of a cancer cell, either entirely or as a fragment (e.g., MHC or peptide fragment), and which is useful for the preferential targeting of a pharmacological agent to the cancer cell. In some embodiments, a tumor antigen is a marker expressed by both normal cells and cancer cells, e.g., a lineage marker, e.g., CD19 on B cells. In some embodiments, a tumor antigen is a cell surface molecule that is overexpressed in a cancer cell in comparison to a normal cell, for instance, 1-fold over expression, 2-fold overexpression, 3-fold overexpression or more in comparison to a normal cell. In some embodiments, a tumor antigen is a cell surface molecule that is underexpressed in a cancer cell in comparison to a normal cell, for instance, 1-fold underexpression, 2-fold underexpression, 3-fold underexpression or more in comparison to a normal cell. In some embodiments, a tumor antigen is a cell surface molecule that is inappropriately synthesized in the cancer cell, for instance, a molecule that contains deletions, additions or mutations in comparison to the molecule expressed on a normal cell.

In some embodiments, a tumor antigen will be expressed exclusively on the cell surface of a cancer cell, entirely or as a fragment (e.g., MHC or peptide fragment), and not synthesized or expressed on the surface of a normal cell. In some embodiments, the CARs of the present disclosure includes CARs comprising an antigen binding domain (e.g., antibody or antibody fragment) that binds to a tumor antigen or fragment, e.g., a MHC presented peptide.

Normally, peptides derived from endogenous proteins fill the pockets of Major histocompatibility complex (MHC) class I molecules, and are recognized by T cell receptors (TCRs) on CD8+ T lymphocytes. The MHC class I complexes are constitutively expressed by all nucleated cells. In cancer, virus-specific and/or tumor-specific peptide/MHC complexes represent a unique class of cell surface targets for immunotherapy. TCR-like antibodies targeting peptides derived from viral or tumor antigens in the context of human leukocyte antigen (HLA)-A1 or HLA-A2 have been described (see, e.g., Sastry et al., J Virol. 2011 85(5):1935-1942; Sergeeva et al., Blood, 2011 117(16):4262-4272; Verma et al., J Immunol 2010 184(4):2156-2165; Willemsen et al., Gene Ther 2001 8(21):1601-1608; Dao et al., Sci Transl Med 2013 5(176):176ra33; Tassev et al., Cancer Gene Ther 2012 19(2):84-100). For example, TCR-like antibody can be identified from screening a library, such as a human scFv phage displayed library.

The term “tumor-supporting antigen” or “cancer-supporting antigen” interchangeably refer to a molecule (typically a protein, carbohydrate or lipid) that is expressed on the surface of a cell that is, itself, not cancerous, but supports the cancer cells, e.g., by promoting their growth or survival e.g., resistance to immune cells. Exemplary cells of this type include stromal cells and myeloid-derived suppressor cells (MDSCs). The tumor-supporting antigen itself need not play a role in supporting the tumor cells so long as the antigen is present on a cell that supports cancer cells.

The term “flexible polypeptide linker” or “linker” as used in the context of a scFv refers to a peptide linker that consists of amino acids such as glycine and/or serine residues used alone or in combination, to link variable heavy and variable light chain regions together. In one embodiment, the flexible polypeptide linker is a Gly/Ser linker and comprises the amino acid sequence (Gly-Gly-Gly-Ser)n, where n is a positive integer equal to or greater than 1. For example, n=1, n=2, n=3. n=4, n=5 and n=6, n=7, n=8, n=9 and n=10 (SEQ ID NO: 32). In one embodiment, the flexible polypeptide linkers include, but are not limited to, (Gly4 Ser)4 (SEQ ID NO: 34) or (Gly4 Ser)3 (SEQ ID NO: 35). In another embodiment, the linkers include multiple repeats of (Gly2Ser), (GlySer) or (Gly3Ser) (SEQ ID NO: 36). Also included within the scope of the disclosure are linkers described in WO2012/138475, incorporated herein by reference).

As used herein in connection with a messenger RNA (mRNA), a 5′ cap (also termed an RNA cap, an RNA 7-methylguanosine cap or an RNA m7G cap) is a modified guanine nucleotide that has been added to the “front” or 5′ end of a eukaryotic messenger RNA shortly after the start of transcription. The 5′ cap consists of a terminal group which is linked to the first transcribed nucleotide. Its presence is critical for recognition by the ribosome and protection from RNases. Cap addition is coupled to transcription, and occurs co-transcriptionally, such that each influences the other. Shortly after the start of transcription, the 5′ end of the mRNA being synthesized is bound by a cap-synthesizing complex associated with RNA polymerase. This enzymatic complex catalyzes the chemical reactions that are required for mRNA capping. Synthesis proceeds as a multi-step biochemical reaction. The capping moiety can be modified to modulate functionality of mRNA such as its stability or efficiency of translation.

›DEFINITIONS · 12 of 13

As used herein, “in vitro transcribed RNA” refers to RNA, preferably mRNA, that has been synthesized in vitro. Generally, the in vitro transcribed RNA is generated from an in vitro transcription vector. The in vitro transcription vector comprises a template that is used to generate the in vitro transcribed RNA.

As used herein, a “poly(A)” is a series of adenosines attached by polyadenylation to the mRNA. In the preferred embodiment of a construct for transient expression, the polyA is between 50 and 5000 (SEQ ID NO: 10517), preferably greater than 64, more preferably greater than 100, most preferably greater than 300 or 400. Poly(A) sequences can be modified chemically or enzymatically to modulate mRNA functionality such as localization, stability or efficiency of translation.

As used herein, “polyadenylation” refers to the covalent linkage of a polyadenylyl moiety, or its modified variant, to a messenger RNA molecule. In eukaryotic organisms, most messenger RNA (mRNA) molecules are polyadenylated at the 3′ end. The 3′ poly(A) tail is a long sequence of adenine nucleotides (often several hundred) added to the pre-mRNA through the action of an enzyme, polyadenylate polymerase. In higher eukaryotes, the poly(A) tail is added onto transcripts that contain a specific sequence, the polyadenylation signal. The poly(A) tail and the protein bound to it aid in protecting mRNA from degradation by exonucleases. Polyadenylation is also important for transcription termination, export of the mRNA from the nucleus, and translation. Polyadenylation occurs in the nucleus immediately after transcription of DNA into RNA, but additionally can also occur later in the cytoplasm. After transcription has been terminated, the mRNA chain is cleaved through the action of an endonuclease complex associated with RNA polymerase. The cleavage site is usually characterized by the presence of the base sequence AAUAAA near the cleavage site. After the mRNA has been cleaved, adenosine residues are added to the free 3′ end at the cleavage site.

As used herein, “transient” refers to expression of a non-integrated transgene for a period of hours, days or weeks, wherein the period of time of expression is less than the period of time for expression of the gene if integrated into the genome or contained within a stable plasmid replicon in the host cell.

As used herein, the terms “treat”, “treatment” and “treating” refer to a partial or complete reduction or amelioration of the progression, severity and/or duration of a proliferative disorder, or the amelioration of one or more symptoms (preferably, one or more discernible symptoms) of a proliferative disorder resulting from the administration of one or more therapies (e.g., one or more therapeutic agents such as a CAR of the disclosure). In specific embodiments, the terms “treat”, “treatment” and “treating” refer to the amelioration of at least one measurable physical parameter of a proliferative disorder, such as growth of a tumor, as well as parameters not necessarily discernible by the patient. In other embodiments the terms “treat”, “treatment” and “treating”-refer to the inhibition of the progression of a proliferative disorder, such as stabilization of a tumor size, either physically by, e.g., stabilization of a discernible symptom, physiologically by, e.g., stabilization of a physical parameter, or both. In other embodiments the terms “treat”, “treatment” and “treating” refer to the reduction or stabilization of tumor size or cancerous cell count.

A “signal transduction pathway” refers to the biochemical relationship between two or more signal transduction molecules that play a role in the transmission of a signal from one portion of a cell to another portion of the cell or to another cell. The phrase “cell surface receptor” includes molecules and complexes of molecules capable of receiving a signal and transmitting signal across the membrane of a cell.

A “subject” is intended to include living organisms in which an immune response can be elicited (e.g., a mammal such as a human).

A “substantially purified” cell refers to a cell that is essentially free of other cell types. A substantially purified cell also refers to a cell which has been separated from other cell types with which it is normally associated in its naturally occurring state. In some instances, a population of substantially purified cells refers to a homogenous population of cells. In other instances, this term refers simply to cell that have been separated from the cells with which they are naturally associated in their natural state. In some aspects, the cells are cultured in vitro. In other aspects, the cells are not cultured in vitro.

A “therapeutic” as used herein means a treatment. A therapeutic effect is obtained by partial or complete reduction, suppression, remission, or eradication of a disease state or symptom.

The term “prophylaxis” as used herein means the partial or complete prevention of or protective treatment for a disease or disease state.

In the context of the present disclosure, “tumor antigen” or “hyperproliferative disorder antigen” or “antigen associated with a hyperproliferative disorder” refers to antigens that are common to specific hyperproliferative disorders. In certain aspects, the hyperproliferative disorder antigens of the present disclosure are derived from, cancers including but not limited to primary or metastatic melanoma, thymoma, lymphoma, sarcoma, lung cancer, liver cancer, non-Hodgkin lymphoma, Hodgkin lymphoma, leukemias, uterine cancer, cervical cancer, bladder cancer, kidney cancer and adenocarcinomas such as breast cancer, prostate cancer, ovarian cancer, pancreatic cancer, and the like.

The term “transfected” or “transformed” or “transduced” refers to a process by which exogenous nucleic acid is transferred or introduced into the host cell. A “transfected” or “transformed” or “transduced” cell is one which has been transfected, transformed or transduced with exogenous nucleic acid. The cell includes the primary subject cell and its progeny.

›DEFINITIONS · 13 of 13

The term “specifically binds,” refers to a molecule that preferentially recognizes and binds a binding partner (e.g., a protein or nucleic acid) over other molecules present in a sample.

“Membrane anchor” or “membrane tethering domain”, as that term is used herein, refers to a polypeptide or moiety, e.g., a myristoyl group, sufficient to anchor an extracellular or intracellular domain to the plasma membrane.

The term “bioequivalent” refers to an amount of an agent other than the reference compound (e.g., RAD001), required to produce an effect equivalent to the effect produced by the reference dose or reference amount of the reference compound (e.g., RAD001). In an embodiment the effect is the level of mTOR inhibition, e.g., as measured by P70 S6 kinase inhibition, e.g., as evaluated in an in vivo or in vitro assay, e.g., as measured by an assay described herein, e.g., the Boulay assay. In an embodiment, the effect is alteration of the ratio of PD-1 positive/PD-1 negative T cells, as measured by cell sorting. In an embodiment a bioequivalent amount or dose of an mTOR inhibitor is the amount or dose that achieves the same level of P70 S6 kinase inhibition as does the reference dose or reference amount of a reference compound. In an embodiment, a bioequivalent amount or dose of an mTOR inhibitor is the amount or dose that achieves the same level of alteration in the ratio of PD-1 positive/PD-1 negative T cells as does the reference dose or reference amount of a reference compound.

The term “low, immune enhancing, dose” when used in conjunction with an mTOR inhibitor, e.g., an allosteric mTOR inhibitor, e.g., RAD001 or rapamycin, or a catalytic mTOR inhibitor, refers to a dose of mTOR inhibitor that partially, but not fully, inhibits mTOR activity, e.g., as measured by the inhibition of P70 S6 kinase activity. Methods for evaluating mTOR activity, e.g., by inhibition of P70 S6 kinase, are discussed herein. The dose is insufficient to result in complete immune suppression but is sufficient to enhance the immune response. In an embodiment, the low, immune enhancing, dose of mTOR inhibitor results in a decrease in the number of PD-1 positive T cells and/or an increase in the number of PD-1 negative T cells, or an increase in the ratio of PD-1 negative T cells/PD-1 positive T cells. In an embodiment, the low, immune enhancing, dose of mTOR inhibitor results in an increase in the number of naive T cells. In an embodiment, the low, immune enhancing, dose of mTOR inhibitor results in one or more of the following:

an increase in the expression of one or more of the following markers: CD62Lhigh, CD127high, CD27+, and BCL2, e.g., on memory T cells, e.g., memory T cell precursors; a decrease in the expression of KLRG1, e.g., on memory T cells, e.g., memory T cell precursors; and an increase in the number of memory T cell precursors, e.g., cells with any one or combination of the following characteristics: increased CD62Lhigh, increased CD127high, increased CD27+, decreased KLRG1, and increased BCL2; wherein any of the changes described above occurs, e.g., at least transiently, e.g., as compared to a non-treated subject.

“Refractory” as used herein refers to a disease, e.g., cancer, that does not respond to a treatment. In embodiments, a refractory cancer can be resistant to a treatment before or at the beginning of the treatment. In other embodiments, the refractory cancer can become resistant during a treatment. A refractory cancer is also called a resistant cancer.

“Relapsed” as used herein refers to the return of a disease (e.g., cancer) or the signs and symptoms of a disease such as cancer after a period of improvement, e.g., after prior treatment of a therapy, e.g., cancer therapy.

Ranges: throughout this disclosure, various aspects of the disclosure can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. As another example, a range such as 95-99% identity, includes something with 95%, 96%, 97%, 98% or 99% identity, and includes subranges such as 96-99%, 96-98%, 96-97%, 97-99%, 97-98% and 98-99% identity. This applies regardless of the breadth of the range. All specified ranges also include the endpoints unless otherwise stated.

›DETAILED DESCRIPTION · 1 of 9

The gRNA molecules, compositions and methods described herein relate to genome editing, for example, gene editing in eukaryotic cells, in particular at a tet gene intron or intron-exon junction, for example at a TET2 intron or intron-exon junction, for example, using a CRISPR/Cas system, e.g., a Cas9 system, e.g., described herein. In particular embodiments, the gRNA molecules, compositions and methods described herein provide for the targeting of a CRISPR system to a target sequence of an intron, or intron-exon junction of a tet gene, for example a tet2 gene. In further aspects, the disclosure provides for modification (e.g., insertion or deletion) of a target sequence of an intron or intron-exon junction of a tet gene, for example, a tet2 gene. In further aspects, the disclosure provides for insertion of a nucleic acid sequence encoding a heterologous protein, for example a CAR molecule, for example as described herein, at or near the target sequence bound by a gene editing system, e.g., bound by a gRNA molecule described herein, e.g., at an intron, or intron-exon junction, of a tet gene, for example a tet2 gene. Such nucleic acid sequence encoding a heterologous protein may be separately introduced into the cell as a template nucleic acid as described herein, for example, including homology arms, or as part of a vector, or introduced at the same time as the gene editing system.

Missense, nonsense, and frameshift mutations (i.e., loss-of-function mutations) in the TET2 gene are associated with various cancers, e.g., hematological cancers. See, e.g., Pan et al., IUBMB Life 67(6): 438-45 (June 2015). Nevertheless, without being bound by theory, the disclosure is based in part on the finding that a CAR gene insertion into the TET2 gene, and in particular into an intron of the TET2 gene, for example the intron between exon 9 and exon 10, results in a CAR-expressing T cell with improved properties. For instance, in some embodiments, a CART cell comprising a CAR gene inserted into one or more copies of the TET2 gene, e.g., an intron of the TET2 gene, is capable of disrupting the expression and/or function of TET2. In some embodiments, the resulting CART cell with TET2 loss-of-function surprisingly is capable of avoiding uncontrolled proliferation and useful in the treatment of cancer, e.g., hematological cancers.

Without being bound by theory, the insertion of a CAR gene into one or more alleles of the TET2 gene, e.g., an intron of the TET2 gene, may be capable of producing a truncated and/or dominant negative form of TET2 that is capable of partially or fully disrupting full-length form(s) of TET2.

The disclosure is further based in part on the discovery that partial (but not full) inhibition of the function and/or expression of TET2 may be beneficial to immune effector cell function. In some embodiments, a CAR gene insertion into the TET2 gene, e.g., an intron of the TET2 gene, disrupts one allele of the TET2 gene and results in partial inhibition of the function and/or expression of TET2. In some embodiments, a CAR gene insertion into the TET2 gene, e.g., an intron of the TET2 gene, disrupts both alleles of the TET2 gene and results in full inhibition of the function and/or expression of TET2. The disclosure is also based in part on the recognition of the need for targeted insertion of nucleic acid encoding a heterologous protein, for example a CAR molecule, for example as described herein, into the genome of a cell, for example an immune effector cell, for example specifically at an intron of a tet gene, e.g., at in intron of a TET2 gene, e.g., at the intron between exon 9 and exon 10 of TET2. Thus, in an aspect, the disclosure provides gene editing systems, gRNA molecules, CRISPR systems and methods useful for insertion of nucleic acid sequence encoding a heterologous protein, for example a CAR molecule, for example as described herein, within an intron of the TET2 gene of a cell, for example an immune effector cell, for example as described herein.

The disclosure is further based in part on the discovery that targeting an intron, e.g., the intron between exon 9 and exon 10 of TET2, may provide a number of advantages. First, for example, the disclosure provides gRNAs that are able to create indels, including 1- or 2-nucleotide deletion indels, at or near target sequences with surprisingly high frequencies, and in particular, combining CRISPR systems comprising these gRNA molecules with a template nucleic acid, e.g., a template nucleic acid encoding a CAR (e.g., as described herein), results in unexpectedly and surprisingly high frequencies of incorporation of sequence of the template nucleic acid at or near the site targeted by the gRNA molecule. These indels and insertions (e.g., insertions of sequence of the template nucleic acid), when created within an exon, can lead to a frameshift mutation and thus significant (e.g., total) inhibition of expression of the protein encoded by the gene. Because of the high frequency of indel formation by these gRNAs, such frameshifts can occur at both alleles of the gene in a high percentage of the cells. Without being bound by theory, targeting an intron sequence with a CRISPR system as disclosed herein, particularly as a site for insertion of nucleic acid encoding a heterologous protein (e.g., sequence of a template nucleic acid), may therefore be beneficial where reduced, but not eliminated, function and/or expression of the target gene is desired because, for example, indels of less than 50 nt, 100 nt, or 150 nt in an intronic region, even if occurring at both alleles of the gene, are not expected to disrupt expression of the functional protein. Because insertion may be a relatively low-frequency event, insertion of the nucleic acid encoding the heterologous protein (e.g., CAR molecule as described herein) may occur in most cells at only one allele of the gene targeted by the CRISPR system. In some embodiments, targeting an intron with a CRISPR system allows for targeted insertion of nucleic acid encoding a heterologous sequence (e.g., CAR molecule, e.g., as described herein) while preserving at least a portion of the expression and/or function of the gene, for example, through the allele which does not comprise the inserted nucleic acid sequence. In alternate embodiments, for example, using the gRNA molecules described herein which result in a surprisingly high rate of incorporation of sequence of the template nucleic acid, targeting an intron with a CRISPR system (e.g., as described herein) allows for targeted insertion of nucleic acid encoding a heterologous sequence (e.g., CAR molecule, e.g., as described herein) while disrupting the expression and/or function of both alleles of the gene. In an aspect, the cell is an immune effector cell, e.g., an NK cell or T cell. In an aspect, the cell is an autologous cell.

›DETAILED DESCRIPTION · 2 of 9

Thus, in an aspect, the disclosure provides a cell, e.g., an immune effector cell, e.g., an immune effector cell comprising a CAR molecule, comprising an indel at or near a target sequence within an intron of a Tet gene, for example within an intron of a Tet2 gene. In an aspect, the disclosure provides a cell, e.g., an immune effector cell, e.g., an immune effector cell comprising a CAR molecule, comprising an indel at or near a target sequence complementary to the targeting domain of a gRNA molecule to a Tet intron sequence, e.g., a Tet2 intron sequence, e.g., complementary to the targeting domain of a gRNA molecule described herein. In an aspect, the disclosure provides a cell, e.g., an immune effector cell, e.g., an immune effector cell comprising a CAR molecule, comprising nucleic acid sequence encoding a heterologous protein (e.g., a CAR molecule, e.g., described herein) integrated into the genome of said cell at or near a target sequence complementary to the targeting domain of a gRNA molecule to a Tet intron sequence, e.g., Tet2 intron sequence, or intron-exon junction sequence, e.g., complementary to the targeting domain of a gRNA molecule described herein. The disclosure further provides methods and compositions useful in connection with said cells

In any of the aforementioned aspects and embodiments the cell is an autologous cell. Alternatively, In any of the aforementioned aspects and embodiments, the cell is an allogeneic cell. Examples of allogenic cells include those in which expression and/or function of a T cell receptor chain, for example, TRAC or TRBC, has been reduced or eliminated, for example using a genome editing system (e.g., CRISPR system) targeted to said gene. The cell may further comprise reduced or eliminated expression of one or more additional genes, for example, B2M and/or CIITA. In any of the aforementioned embodiments and aspects, the cell is or will be engineered to express a chimeric antigen receptor (CAR), e.g., as described herein. In any of the aforementioned aspects and embodiments, the cell is a T cell.

Additional features of the gene editing systems, gRNA molecules, the CRISPR systems, Cas9 molecules, cells, CAR molecules, methods and other aspects of the disclosure are described in detail below.

Gene Editing Systems

In an aspect, the disclosure provides gene editing systems which target a TET, e.g., TET2, intron sequence, e.g., a sequence selected from the sequences listed in Table 3. Various gene editing systems are described more fully below.

In some embodiments, the disclosure provides gene editing systems comprising a template nucleic acid encoding a CAR and capable of integrating a CAR nucleic acid sequence such that CAR is expressed and/or TET, e.g., TET2, is disrupted. In some embodiments, the TET, e.g., TET2, is partially disrupted. In some embodiments, the TET, e.g., TET2, is fully disrupted. In some embodiments, only one allele of TET, e.g., TET2, is modified. In some embodiments, both alleles of TET, e.g., TET2, are modified.

TALEN Gene Editing Systems

TALENs are produced artificially by fusing a TAL effector DNA binding domain to a DNA cleavage domain. Transcription activator-like effects (TALEs) can be engineered to bind any desired DNA sequence, including a sequence of a TET2 intron, e.g., a sequence within a sequence of Table 3. By combining an engineered TALE with a DNA cleavage domain, a restriction enzyme can be produced which is specific to any desired DNA sequence, including a TET2 intron. These can then be introduced into a cell, wherein they can be used for genome editing. Boch (2011) Nature Biotech. 29: 135-6; and Boch et al. (2009) Science 326: 1509-12; Moscou et al. (2009) Science 326: 3501.

TALEs are proteins secreted by Xanthomonas bacteria. The DNA binding domain contains a repeated, highly conserved 33-34 amino acid sequence, with the exception of the 12th and 13th amino acids. These two positions are highly variable, showing a strong correlation with specific nucleotide recognition. They can thus be engineered to bind to a desired DNA sequence.

To produce a TALEN, a TALE protein is fused to a nuclease (N), which is, for example, a wild-type or mutated FokI endonuclease. Several mutations to FokI have been made for its use in TALENs; these, for example, improve cleavage specificity or activity. Cermak et al. (2011) Nucl. Acids Res. 39: e82; Miller et al. (2011) Nature Biotech. 29: 143-8; Hockemeyer et al. (2011) Nature Biotech. 29: 731-734; Wood et al. (2011) Science 333: 307; Doyon et al. (2010) Nature Methods 8: 74-79; Szczepek et al. (2007) Nature Biotech. 25: 786-793; and Guo et al. (2010) J. Mol. Biol. 200: 96.

The FokI domain functions as a dimer, requiring two constructs with unique DNA binding domains for sites in the target genome with proper orientation and spacing. Both the number of amino acid residues between the TALE DNA binding domain and the FokI cleavage domain and the number of bases between the two individual TALEN binding sites appear to be important parameters for achieving high levels of activity. Miller et al. (2011) Nature Biotech. 29: 143-8.

A TALEN to a TET2 intron sequence, e.g., a sequence listed in Table 3, can be used inside a cell to produce a double-stranded break (DSB). A mutation can be introduced at the break site if the repair mechanisms improperly repair the break via non-homologous end joining. For example, improper repair may introduce a frame shift mutation. Alternatively, template nucleic acid, e.g., as described herein, can be introduced into the cell along with the TALEN, e.g., template nucleic acid encoding a CAR, e.g., as described herein; depending on the sequences of the template nucleic acid and chromosomal sequence, this process can be used to integrate heterologous nucleic acid sequence, e.g., sequence encoding the CAR, e.g., as described herein, at or near the site targeted by the TALEN. Without being bound by theory, such integration may lead to the expression of the CAR as well as disruption, e.g., partial disruption, e.g., disruption of one or more functions, e.g., disruption of only one allele of, TET2. In some embodiments, both alleles of TET, e.g., TET2, are disrupted.

›DETAILED DESCRIPTION · 3 of 9

TALENs specific to sequences in TET2 introns, can be constructed using any method known in the art, including various schemes using modular components. Zhang et al. (2011) Nature Biotech. 29: 149-53; Geibler et al. (2011) PLoS ONE 6: e19509; U.S. Pat. Nos. 8,420,782; 8,470,973, the contents of which are hereby incorporated by reference in their entirety.

Zinc Finger Nuclease (“ZFN”) Gene Editing Systems to a TET2 Intron

“ZFN” or “zinc finger nuclease” refers to an artificial nuclease which can be used to modify, e.g., delete one or more nucleic acids of, a desired nucleic acid sequence, e.g., a TET2 intron, e.g., a sequence listed in Table 3. Mutant and variant ZFNs are also encompassed.

Like a TALEN, a ZFN comprises a FokI nuclease domain (or derivative thereof) fused to a DNA-binding domain. In the case of a ZFN, the DNA-binding domain comprises one or more zinc fingers. Carroll et al. (2011) Genetics Society of America 188: 773-782; and Kim et al. (1996) Proc. Natl. Acad. Sci. USA 93: 1156-1160.

A zinc finger is a small protein structural motif stabilized by one or more zinc ions. A zinc finger can comprise, for example, Cys2His2, and can recognize an approximately 3-bp sequence. Various zinc fingers of known specificity can be combined to produce multi-finger polypeptides which recognize about 6, 9, 12, 15 or 18-bp sequences. Various selection and modular assembly techniques are available to generate zinc fingers (and combinations thereof) recognizing specific sequences, including phage display, yeast one-hybrid systems, bacterial one-hybrid and two-hybrid systems, and mammalian cells.

Like a TALEN, a ZFN must dimerize to cleave DNA. Thus, a pair of ZFNs are required to target non-palindromic DNA sites. The two individual ZFNs must bind opposite strands of the DNA with their nucleases properly spaced apart. Bitinaite et al. (1998) Proc. Natl. Acad. Sci. USA 95: 10570-5.

Also like a TALEN, a ZFN can create a double-stranded break in the DNA, which can create a frame-shift mutation if improperly repaired, leading to a decrease in the expression and/or function, e.g., one or more functions, of TET2, e.g., from one allele, in a cell. ZFNs can also be used with homologous recombination to mutate the TET2 intron, or to introduce nucleic acid, e.g., encoding a CAR, at or near a site of the target sequence. As discussed above, the nucleic acid encoding a CAR may be introduced as part of a template nucleic acid. In embodiments, the template nucleic acid further comprises homology arms 5′ to, 3′ to, or both 5′ and 3′ to the nucleic acid of the template nucleic acid which encodes the molecule or molecules of interest (e.g., which encodes a CAR described herein), wherein said homology arms are complementary to genomic DNA sequence flanking the target sequence.

ZFNs specific to sequences in a TET2 intron, e.g., a sequence of Table 3, can be constructed using any method known in the art. See, e.g., Provasi (2011) Nature Med. 18: 807-815; Torikai (2013) Blood 122: 1341-1349; Cathomen et al. (2008) Mol. Ther. 16: 1200-7; and Guo et al. (2010) J. Mol. Biol. 400: 96; U.S. Patent Publication 2011/0158957; and U.S. Patent Publication 2012/0060230, the contents of which are hereby incorporated by reference in their entirety. In embodiments, The ZFN gene editing system may also comprise nucleic acid encoding one or more components of the ZFN gene editing system, e.g., a ZFN gene editing system targeted to a TET2 intron, e.g., a sequence listed in Table 3.

In a preferred aspect, the gene editing system is a CRISPR system. Additional features of the gRNA molecules, the CRISPR systems, Cas9 molecules, cells, CAR molecules, methods and other aspects of the disclosure are described in detail below.

I. gRNA Molecules

A gRNA molecule may have a number of domains, as described more fully below; however, a gRNA molecule typically comprises at least a crRNA domain (comprising a targeting domain) and a tracr. In embodiments, the crRNA and the tracr are provided on a single contiguous polynucleotide molecule. In other embodiments, the crRNA and the tracr are provided on separate polynucleotide molecules, which are themselves capable of association, e.g., through non-covalent hybridization. The gRNA molecules, used as a component of a CRISPR system, are useful for modifying (e.g., modifying the sequence) DNA at or near a target site. Such modifications include deletions and or insertions that result in, for example, reduced or eliminated expression of a functional product of the gene comprising the target site. Such modifications can also include insertion of heterologous nucleic acid sequence, for example, nucleic acid sequence encoding a heterologous protein (e.g., a CAR molecule, e.g., as described herein), that may be provided to said cell as a template nucleic acid, as described herein. In some embodiments, the inserted heterologous nucleic acid also serves to eliminate expression of the functional product of the gene comprising the target site. In some embodiments, a separate gRNA molecule and CRISPR system are used to eliminate expression of the functional product of the gene comprising the target site before, at the same time as, or after the insertion of the heterologous nucleic acid. These uses, and others, are described more fully below.

In an embodiment, a unimolecular, or sgRNA comprises, preferably from 5′ to 3′: a crRNA (which comprises a targeting domain complementary to a target sequence and a region that forms part of a flagpole (i.e., a crRNA flagpole region)); a loop; and a tracr (which comprises a domain complementary to the crRNA flagpole region, and a domain which additionally binds a nuclease or other effector molecule, e.g., a Cas molecule, e.g., a Cas9 molecule), and may take the following format (from 5′ to 3′):

[targeting domain]-[crRNA flagpole region]-[optional first flagpole extension]-[loop]-[optional first tracr extension]-[tracr flagpole region]-[tracr nuclease binding domain].

In embodiments, the tracr nuclease binding domain binds to a Cas protein, e.g., a Cas9 protein.

›DETAILED DESCRIPTION · 4 of 9

In an embodiment, a bimolecular, or dgRNA comprises two polynucleotides; the first, preferably from 5′ to 3′: a crRNA (which contains a targeting domain complementary to a target sequence and a region that forms part of a flagpole; and the second, preferably from 5′ to 3′: a tracr (which contains a domain complementary to the crRNA flagpole region, and a domain which additionally binds a nuclease or other effector molecule, e.g., a Cas molecule, e.g., Cas9 molecule), and may take the following format (from 5′ to 3′):

Polynucleotide 1 (crRNA): [targeting domain]-[crRNA flagpole region]-[optional first flagpole extension]-[optional second flagpole extension] Polynucleotide 2 (tracr): [optional first tracr extension]-[tracr flagpole region]-[tracr nuclease binding domain]

In embodiments, the tracr nuclease binding domain binds to a Cas protein, e.g., a Cas9 protein.

In some aspects, the targeting domain comprises or consists of a targeting domain sequence described herein, e.g., a targeting domain described in Table 1 or, preferably, a targeting domain described in Table 2, or a targeting domain comprising or consisting of 17, 18, 19, or 20 (preferably 20) consecutive nucleotides of a targeting domain sequence described in Table 1, or Table 2.

In some aspects, the flagpole, e.g., the crRNA flagpole region, comprises, from 5′ to 3′: GUUUUAGAGCUA (SEQ ID NO: 50).

In some aspects, the flagpole, e.g., the crRNA flagpole region, comprises, from 5′ to 3′: GUUUAAGAGCUA (SEQ ID NO: 51).

In some aspects the loop comprises, from 5′ to 3′: GAAA (SEQ ID NO: 52).

In some aspects the tracr comprises, from 5′ to 3′: UAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAG UCGGUGC (SEQ ID NO: 53) and is preferably used in a gRNA molecule comprising SEQ ID NO: 50.

In some aspects the tracr comprises, from 5′ to 3′: UAGCAAGUUUAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAG UCGGUGC (SEQ ID NO: 54) and is preferably used in a gRNA molecule comprising SEQ ID NO: 51.

In some aspects, the gRNA may also comprise, at the 3′ end, additional U nucleic acids. For example the gRNA may comprise an additional 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 U nucleic acids at the 3′ end (SEQ ID NO: 58). In an embodiment, the gRNA comprises an additional 4 U nucleic acids at the 3′ end. In the case of dgRNA, one or more of the polynucleotides of the dgRNA (e.g., the polynucleotide comprising the targeting domain and the polynucleotide comprising the tracr) may comprise, at the 3′ end, additional U nucleic acids. For example, the case of dgRNA, one or more of the polynucleotides of the dgRNA (e.g., the polynucleotide comprising the targeting domain and the polynucleotide comprising the tracr) may comprise an additional 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 U nucleic acids at the 3′ end (SEQ ID NO: 58). In an embodiment, in the case of dgRNA, one or more of the polynucleotides of the dgRNA (e.g., the polynucleotide comprising the targeting domain and the polynucleotide comprising the tracr) comprises an additional 4 U nucleic acids at the 3′ end. In an embodiment of a dgRNA, only the polynucleotide comprising the tracr comprises the additional U nucleic acid(s), e.g., 4 U nucleic acids. In an embodiment of a dgRNA, only the polynucleotide comprising the targeting domain comprises the additional U nucleic acid(s). In an embodiment of a dgRNA, both the polynucleotide comprising the targeting domain and the polynucleotide comprising the tracr comprise the additional U nucleic acids, e.g., 4 U nucleic acids.

In some aspects, the gRNA may also comprise, at the 3′ end, additional A nucleic acids. For example the gRNA may comprise an additional 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 A nucleic acids at the 3′ end (SEQ ID NO: 59). In an embodiment, the gRNA comprises an additional 4 A nucleic acids at the 3′ end. In the case of dgRNA, one or more of the polynucleotides of the dgRNA (e.g., the polynucleotide comprising the targeting domain and the polynucleotide comprising the tracr) may comprise, at the 3′ end, additional A nucleic acids. For example, the case of dgRNA, one or more of the polynucleotides of the dgRNA (e.g., the polynucleotide comprising the targeting domain and the polynucleotide comprising the tracr) may comprise an additional 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 A nucleic acids at the 3′ end (SEQ ID NO: 59). In an embodiment, in the case of dgRNA, one or more of the polynucleotides of the dgRNA (e.g., the polynucleotide comprising the targeting domain and the polynucleotide comprising the tracr) comprises an additional 4 A nucleic acids at the 3′ end. In an embodiment of a dgRNA, only the polynucleotide comprising the tracr comprises the additional A nucleic acid(s), e.g., 4 A nucleic acids. In an embodiment of a dgRNA, only the polynucleotide comprising the targeting domain comprises the additional A nucleic acid(s). In an embodiment of a dgRNA, both the polynucleotide comprising the targeting domain and the polynucleotide comprising the tracr comprise the additional U nucleic acids, e.g., 4 A nucleic acids.

In embodiments, one or more of the polynucleotides of the gRNA molecule may comprise a cap at the 5′ end.

In an embodiment, a unimolecular, or sgRNA comprises, preferably from 5′ to 3′: a crRNA (which contains a targeting domain complementary to a target sequence; a crRNA flagpole region; first flagpole extension; a loop; a first tracr extension (which contains a domain complementary to at least a portion of the first flagpole extension); and a tracr (which contains a domain complementary to the crRNA flagpole region, and a domain which additionally binds a Cas9 molecule). In some aspects, the targeting domain comprises a targeting domain sequence described herein, e.g., a targeting domain described in Table 1 or Table 2, or a targeting domain comprising or consisting of 17, 18, 19, 20 (preferably 20) consecutive nucleotides of a targeting domain sequence described in Table 1 or Table 2, for example the 3′ 17, 18, 19 or 20 (preferably 20) consecutive nucleotides of a targeting domain sequence described in Table 1 or Table 2.

›DETAILED DESCRIPTION · 5 of 9

In aspects comprising a first flagpole extension and/or a first tracr extension, the flagpole, loop and tracr sequences may be as described above. In general any first flagpole extension and first tracr extension may be employed, provided that they are complementary. In embodiments, the first flagpole extension and first tracr extension consist of 3, 4, 5, 6, 7, 8, 9, 10 or more complementary nucleotides.

In some aspects, the first flagpole extension comprises, from 5′ to 3′: UGCUG (SEQ ID NO: 55). In some aspects, the first flagpole extension consists of SEQ ID NO: 55.

In some aspects, the first tracr extension comprises, from 5′ to 3′: CAGCA (SEQ ID NO: 56). In some aspects, the first tracr extension consists of SEQ ID NO: 56.

In an embodiment, a dgRNA comprises two nucleic acid molecules. In some aspects, the dgRNA comprises a first nucleic acid which contains, preferably from 5′ to 3′: a targeting domain complementary to a target sequence; a crRNA flagpole region; optionally a first flagpole extension; and, optionally, a second flagpole extension; and a second nucleic acid (which may be referred to herein as a tracr), and comprises at least a domain which binds a Cas molecule, e.g., a Cas9 molecule) comprising preferably from 5′ to 3′: optionally a first tracr extension; and a tracr (which contains a domain complementary to the crRNA flagpole region, and a domain which additionally binds a Cas, e.g., Cas9, molecule). The second nucleic acid may additionally comprise, at the 3′ end (e.g., 3′ to the tracr) additional U nucleic acids. For example the tracr may comprise an additional 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 U nucleic acids at the 3′ end (e.g., 3′ to the tracr) (SEQ ID NO: 58). The second nucleic acid may additionally or alternately comprise, at the 3′ end (e.g., 3′ to the tracr) additional A nucleic acids. For example the tracr may comprise an additional 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 A nucleic acids at the 3′ end (e.g., 3′ to the tracr) (SEQ ID NO: 59). In some aspects, the targeting domain comprises a targeting domain sequence described herein, e.g., a targeting domain described in Table 1 or Table 2, or a targeting domain comprising or consisting of 17, 18, 19, or 20 (preferably 20) consecutive nucleotides of a targeting domain sequence described in Table 1 or Table 2.

In aspects involving a dgRNA, the crRNA flagpole region, optional first flagpole extension, optional first tracr extension and tracr sequences may be as described above.

In some aspects, the optional second flagpole extension comprises, from 5′ to 3′: UUUUG (SEQ ID NO: 57).

In embodiments, the 3′ 1, 2, 3, 4, or 5 nucleotides, the 5′ 1, 2, 3, 4, or 5 nucleotides, or both the 3′ and 5′ 1, 2, 3, 4, or 5 nucleotides of the gRNA molecule (and in the case of a dgRNA molecule, the polynucleotide comprising the targeting domain and/or the polynucleotide comprising the tracr) are modified nucleic acids, as described more fully in section XIII, below.

The domains are discussed briefly below:

1) The Targeting Domain:

Guidance on the selection of targeting domains can be found, e.g., in Fu Y el al. NAT BIOTECHNOL 2014 (doi: 10.1038/nbt.2808) and Sternberg S H el al. NATURE 2014 (doi: 10.1038/nature13011).

The targeting domain comprises a nucleotide sequence that is complementary, e.g., at least 80, 85, 90, 95, or 99% complementary, or e.g., fully complementary, to the target sequence on the target nucleic acid. The targeting domain is part of an RNA molecule and will therefore comprise the base uracil (U), while any DNA encoding the gRNA molecule will comprise the base thymine (T). While not wishing to be bound by theory, it is believed that the complementarity of the targeting domain with the target sequence contributes to specificity of the interaction of the gRNA molecule/Cas9 molecule complex with a target nucleic acid. It is understood that in a targeting domain and target sequence pair, the uracil bases in the targeting domain will pair with the adenine bases in the target sequence.

In an embodiment, the targeting domain is 5 to 50, e.g., 10 to 40, e.g., 10 to 30, e.g., 15 to 30, e.g., 15 to 25 nucleotides in length. In an embodiment, the targeting domain is 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 nucleotides in length. In an embodiment, the targeting domain is 16 nucleotides in length. In an embodiment, the targeting domain is 17 nucleotides in length. In an embodiment, the targeting domain is 18 nucleotides in length. In an embodiment, the targeting domain is 19 nucleotides in length. In an embodiment, the targeting domain is 20 nucleotides in length. In an embodiment, the targeting domain is 21 nucleotides in length. In an embodiment, the targeting domain is 22 nucleotides in length. In an embodiment, the targeting domain is 23 nucleotides in length. In an embodiment, the targeting domain is 24 nucleotides in length. In an embodiment, the targeting domain is 25 nucleotides in length. In embodiments, the aforementioned 16, 17, 18, 19, or 20 nucleotides comprise the 5′-16, 17, 18, 19 or 20 nucleotides from a targeting domain described in Table 1 or Table 2. In embodiments, the aforementioned 16, 17, 18, 19, or 20 nucleotides comprise the 3′-16, 17, 18, 19 or 20 nucleotides from a targeting domain described in Table 1 or Table 2. In embodiments, the aforementioned 16, 17, 18, 19, or 20 nucleotides consist of the 3′-16, 17, 18, 19 or 20 nucleotides from a targeting domain described in Table 1 or Table 2. In embodiments, the targeting domain consists of a targeting domain described in Table 1 or Table 2.

Without being bound by theory, it is believed that the 8, 9 or 10 nucleic acids of the targeting domain disposed at the 3′ end of the targeting domain may be important for targeting the target sequence, and may thus be referred to as the “core” region of the targeting domain. In an embodiment, the core domain is fully complementary with the target sequence.

The strand of the target nucleic acid with which the targeting domain is complementary is referred to herein as the target sequence. In some aspects, the target sequence is disposed on a chromosome, e.g., is a target within a gene. In some aspects the target sequence is disposed within an exon of a gene. In some aspects the target sequence is disposed within an intron of a gene. In some aspects, the target sequence comprises, or is proximal (e.g., within 10, 20, 30, 40, 50, 100, 200, 300, 400, 500, or 1000 nucleic acids) to a binding site of a regulatory element, e.g., a promoter or transcription factor binding site, of a gene of interest. Some or all of the nucleotides of the targeting domain can have a modification, e.g., modification found in Section XIII herein.

›DETAILED DESCRIPTION · 6 of 9

2) crRNA Flagpole Region:

The flagpole comprises a portion of gRNA in which the crRNA and the tracr bind or hybridize to one another. The crRNA flagpole region is complementary with a portion of the tracr, and in an embodiment, has sufficient complementarity to a portion of the tracr to form a duplexed region under at least some physiological conditions, for example, normal physiological conditions. In an embodiment, the crRNA flagpole region is 5 to 30 nucleotides in length. In an embodiment, the crRNA flagpole region is 5 to 25 nucleotides in length. The crRNA flagpole region can share homology with, or be derived from, a naturally occurring portion of the repeat sequence from a bacterial CRISPR system. In an embodiment, it has at least 50% homology with a crRNA flagpole region disclosed herein, e.g., an S. pyogenes , or S. thermophilus , crRNA flagpole region.

In an embodiment, the flagpole, e.g., the crRNA flagpole region, comprises SEQ ID NO: 50. In an embodiment, the flagpole, e.g., the crRNA flagpole region, consists of SEQ ID NO: 50. In an embodiment, the flagpole, e.g., the crRNA flagpole region, comprises sequence having at least 50%, 60%, 70%, 80%, 85%, 90%, 95% or 99% homology with SEQ ID NO: 50. In an embodiment, the flagpole, e.g., the crRNA flagpole region, comprises at least 5, 6, 7, 8, 9, 10, or 11 nucleotides of SEQ ID NO: 50. In an embodiment, the flagpole, e.g., the crRNA flagpole region, comprises SEQ ID NO: 51. In an embodiment, the flagpole, e.g., the crRNA flagpole region, consists of SEQ ID NO: 51. In an embodiment, the flagpole comprises sequence having at least 50%, 60%, 70%, 80%, 85%, 90%, 95% or 99% homology with SEQ ID NO: 51. In an embodiment, the flagpole, e.g., the crRNA flagpole region, comprises at least 5, 6, 7, 8, 9, 10, or 11 nucleotides of SEQ ID NO: 51.

Some or all of the nucleotides of the domain can have a modification, e.g., modification described in Section XIII herein.

3) First Flagpole Extension

When a tracr comprising a first tracr extension is used, the crRNA may comprise a first flagpole extension. In general any first flagpole extension and first tracr extension may be employed, provided that they are complementary. In embodiments, the first flagpole extension and first tracr extension consist of 3, 4, 5, 6, 7, 8, 9, 10 or more complementary nucleotides.

The first flagpole extension may comprise nucleotides that are complementary, e.g., 80%, 85%, 90%, 95% or 99%, e.g., fully complementary, with nucleotides of the first tracr extension. In some aspects, the first flagpole extension nucleotides that hybridize with complementary nucleotides of the first tracr extension are contiguous. In some aspects, the first flagpole extension nucleotides that hybridize with complementary nucleotides of the first tracr extension are discontinuous, e.g., comprises two or more regions of hybridization separated by nucleotides that do not base pair with nucleotides of the first tracr extension. In some aspects, the first flagpole extension comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more nucleotides. In some aspects, the first flagpole extension comprises, from 5′ to 3′: UGCUG (SEQ ID NO: 55). In some aspects, the first flagpole extension consists of, from 5′ to 3′: UGCUG (SEQ ID NO: 55). In some aspects, the first flagpole extension consists of SEQ ID NO: 55. In some aspects the first flagpole extension comprises nucleic acid that is at least 80%, 85%, 90%, 95% or 99% homology to SEQ ID NO: 55.

Some or all of the nucleotides of the first tracr extension can have a modification, e.g., modification found in Section XIII herein.

3) The Loop

A loop serves to link the crRNA flagpole region (or optionally the first flagpole extension, when present) with the tracr (or optionally the first tracr extension, when present) of a sgRNA. The loop can link the crRNA flagpole region and tracr covalently or non-covalently. In an embodiment, the linkage is covalent. In an embodiment, the loop covalently couples the crRNA flagpole region and tracr. In an embodiment, the loop covalently couples the first flagpole extension and the first tracr extension. In an embodiment, the loop is, or comprises, a covalent bond interposed between the crRNA flagpole region and the domain of the tracr which hybridizes to the crRNA flagpole region. Typically, the loop comprises one or more, e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides.

In dgRNA molecules the two molecules can be associated by virtue of the hybridization between at least a portion of the crRNA (e.g., the crRNA flagpole region) and at least a portion of the tracr (e.g., the domain of the tracr which is complementary to the crRNA flagpole region).

A wide variety of loops are suitable for use in sgRNAs. Loops can consist of a covalent bond, or be as short as one or a few nucleotides, e.g., 1, 2, 3, 4, or 5 nucleotides in length. In an embodiment, a loop is 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 25 or more nucleotides in length. In an embodiment, a loop is 2 to 50, 2 to 40, 2 to 30, 2 to 20, 2 to 10, or 2 to 5 nucleotides in length. In an embodiment, a loop shares homology with, or is derived from, a naturally occurring sequence. In an embodiment, the loop has at least 50% homology with a loop disclosed herein. In an embodiment, the loop comprises SEQ ID NO: 52. In an embodiment, the loop consists of SEQ ID NO: 52.

Some or all of the nucleotides of the domain can have a modification, e.g., modification described in Section XIII herein.

4) The Second Flagpole Extension

In an embodiment, a dgRNA can comprise additional sequence, 3′ to the crRNA flagpole region or, when present, the first flagpole extension, referred to herein as the second flagpole extension. In an embodiment, the second flagpole extension is 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, or 2-4 nucleotides in length. In an embodiment, the second flagpole extension is 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more nucleotides in length. In an embodiment, the second flagpole extension comprises SEQ ID NO: 57. In an embodiment, the second flagpole extension consists of SEQ ID NO: 57.

›DETAILED DESCRIPTION · 7 of 9

5) The Tracr:

The tracr is a nucleic acid sequence that can provide for nuclease, e.g., Cas9, binding. Without being bound by theory, it is believed that each Cas9 species is associated with a particular tracr sequence. Tracr sequences are utilized in both sgRNA and in dgRNA systems. The exemplary gRNA targeting domain sequences provided in Table 1 and Table 2 may be utilized in both sgRNA and in dgRNA systems.

In an embodiment, the tracr comprises sequence from, or derived from, an S. pyogenes tracr. See Jinek et al. (2012). In some aspects, the tracr has a portion that hybridizes to the flagpole portion of the crRNA, e.g., it has sufficient complementarity to the crRNA flagpole region to form a duplexed region under at least some physiological conditions (sometimes referred to herein as the tracr flagpole region or a tracr domain complementary to the crRNA flagpole region). In embodiments, the domain of the tracr that hybridizes with the crRNA flagpole region comprises at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleotides that hybridize with complementary nucleotides of the crRNA flagpole region. In some aspects, the tracr nucleotides that hybridize with complementary nucleotides of the crRNA flagpole region are contiguous. In some aspects, the tracr nucleotides that hybridize with complementary nucleotides of the crRNA flagpole region are discontinuous, e.g., comprises two or more regions of hybridization separated by nucleotides that do not base pair with nucleotides of the crRNA flagpole region. In some aspects, the portion of the tracr that hybridizes to the crRNA flagpole region comprises, from 5′ to 3′: UAGCAAGUUAAAA (SEQ ID NO: 61). In some aspects, the portion of the tracr that hybridizes to the crRNA flagpole region comprises, from 5′ to 3′: UAGCAAGUUUAAA (SEQ ID NO: 62). In embodiments, the sequence that hybridizes with the crRNA flagpole region is disposed on the tracr 5′- to the sequence of the tracr that additionally binds a nuclease, e.g., a Cas molecule, e.g., a Cas9 molecule.

The tracr further comprises a domain that additionally binds to a nuclease, e.g., a Cas molecule, e.g., a Cas9 molecule. Without being bound by theory, it is believed that Cas9 from different species bind to different tracr sequences. In some aspects, the tracr comprises sequence that binds to a S. pyogenes Cas9 molecule. See Jinek et al. (2012). In some aspects, the tracr comprises sequence that binds to a Cas9 molecule disclosed herein. In some aspects, the domain that additionally binds a Cas9 molecule comprises, from 5′ to 3′: UAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGC (SEQ ID NO: 63). In some aspects the domain that additionally binds a Cas9 molecule comprises, from 5′ to 3′: UAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCUUUU (SEQ ID NO: 64).

In some embodiments, the tracr comprises SEQ ID NO: 53. In some embodiments, the tracr comprises SEQ ID NO: 54. In some embodiments, the tracr consists of SEQ ID NO: 53. In some embodiments, the tracr consists of SEQ ID NO: 54.

Some or all of the nucleotides of the tracr can have a modification, e.g., modification found in Section XIII herein.

In embodiments, the gRNA or any of the gRNA components described above comprises an inverted abasic residue at the 5′ end, the 3′ end or both the 5′ and 3′ end (e.g., in the sgRNA or in the tracr and/or crRNA of a dgRNA). In embodiments, the gRNA or any of the gRNA components described above comprises one or more phosphorothioate bonds. For example, the one or more phosphorothioate bonds can be between residues at the 5′ end of the polynucleotide, for example, a phosphrothioate bond between the first two 5′ residues, between each of the first three 5′ residues, between each of the first four 5′ residues, or between each of the first five 5′ residues (e.g., in the sgRNA or in the tracr and/or crRNA of a dgRNA). In embodiments, the gRNA or gRNA component may alternatively or additionally comprise one or more phosphorothioate bonds between residues at the 3′ end of the polynucleotide, for example, a phosphrothioate bond between the first two 3′ residues, between each of the first three 3′ residues, between each of the first four 3′ residues, or between each of the first five 3′ residues. In an embodiment, the gRNA or gRNA components described above, comprises a phosphorothioate bond between each of the first four 5′ residues (e.g., comprises or consists of, three phosphorothioate bonds at the 5′ end(s)), and a phosphorothioate bond between each of the first four 3′ residues (e.g., comprises or consists of, three phosphorothioate bonds at the 3′ end(s)). In an embodiment, any of the phosphorothioate modifications described above can be combined with an inverted abasic residue at the 5′ end, the 3′ end, or both the 5′ and 3′ ends of the polynucleotide. In such embodiments, the inverted abasic nucleotide may be linked to the 5′ and/or 3′ nucleotide by a phosphate bond or a phosphorothioate bond.

In embodiments, the gRNA or gRNA components described above, comprises one or more nucleotides that include a 2′ O-methyl modification. In embodiments, each of the first 1, 2, 3, or more of the 5′ residues comprise a 2′ O-methyl modification. In embodiments, each of the first 1, 2, 3, or more of the 3′ residues comprise a 2′ O-methyl modification. In embodiments, the 4th-to-terminal, 3 rd -to-terminal, and 2 nd -to-terminal 3′ residues comprise a 2′ O-methyl modification. In embodiments, each of the first 1, 2, 3 or more of the 5′ residues comprise a 2′ O-methyl modification, and each of the first 1, 2, 3 or more of the 3′ residues comprise a 2′ O-methyl modification. In an embodiment, each of the first 3 of the 5′ residues comprise a 2′ O-methyl modification, and each of the first 3 of the 3′ residues comprise a 2′ O-methyl modification. In embodiments, each of the first 3 of the 5′ residues comprise a 2′ O-methyl modification, and the 4th-to-terminal, 3 rd -to-terminal, and 2 nd -to-terminal 3′ residues comprise a 2′ O-methyl modification. In embodiments, any of the 2′ O-methyl modifications described above may be combined with one or more phosphorothioate modifications, e.g., as described above, and/or one or more inverted abasic modifications, e.g., as described above.

›DETAILED DESCRIPTION · 8 of 9

In an embodiment, the gRNA or gRNA components described above, comprises or consists of, a phosphorothioate bond between each of the first four 5′ residues (e.g., comprises or consists of three phosphorothioate bonds at the 5′ end of the polynucleotide(s)), a phosphorothioate bond between each of the first four 3′ residues (e.g., comprises or consists of three phosphorothioate bonds at the 5′ end of the polynucleotide(s)), a 2′ O-methyl modification at each of the first three 5′ residues, and a 2′ O-methyl modification at each of the first three 3′ residues.

In an embodiment, the gRNA or gRNA components described above, comprises or consists of, a phosphorothioate bond between each of the first four 5′ residues (e.g., comprises or consists of three phosphorothioate bonds at the 5′ end of the polynucleotide(s)), a phosphorothioate bond between each of the first four 3′ residues (e.g., comprises or consists of three phosphorothioate bonds at the 5′ end of the polynucleotide(s)), a 2′ O-methyl modification at each of the first three 5′ residues, and a 2′ O-methyl modification at each of the 4 th -to-terminal, 3 rd -to-terminal, and 2 nd -to-terminal 3′ residues.

In an embodiment, the gRNA or gRNA components described above, comprises or consists of, a phosphorothioate bond between each of the first four 5′ residues (e.g., comprises or consists of three phosphorothioate bonds at the 5′ end of the polynucleotide(s)), a phosphorothioate bond between each of the first four 3′ residues (e.g., comprises or consists of three phosphorothioate bonds at the 5′ end of the polynucleotide(s)), a 2′ O-methyl modification at each of the first three 5′ residues, a 2′ O-methyl modification at each of the first three 3′ residues, and an additional inverted abasic residue at each of the 5′ and 3′ ends.

In an embodiment, the gRNA or gRNA components described above, comprises or consists of, a phosphorothioate bond between each of the first four 5′ residues (e.g., comprises or consists of three phosphorothioate bonds at the 5′ end of the polynucleotide(s)), a phosphorothioate bond between each of the first four 3′ residues (e.g., comprises or consists of three phosphorothioate bonds at the 5′ end of the polynucleotide(s)), a 2′ O-methyl modification at each of the first three 5′ residues, and a 2′ O-methyl modification at each of the 4th-to-terminal, 3 rd -to-terminal, and 2 nd -to-terminal 3′ residues, and an additional inverted abasic residue at each of the 5′ and 3′ ends.

Specific embodiments of gRNA molecules are described in detail below. Although each is shown with 20 nucleic acid residues of the targeting domain (N's in each of the sequences below), it will be understood that the targeting domain may comprise or consist of 5-50 residues, e.g., 15-30 residues, e.g., 15-25 residues, e.g., 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 residues. In embodiments, the gRNA is a dgRNA and comprises or consists of:

crRNA:

mN*mN*mN*GUUUUAGAGCUAU*mG*mC*mU (SEQ ID NO: 66), where m indicates a base with 2′O-Methyl modification, * indicates a phosphorothioate bond, and N's indicate the residues of the targeting domain, e.g., as described herein (optionally with an inverted abasic residue at the 5′ and/or 3′ terminus); and tracr:

AACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAA AAGUGGCACCGAGUCGGUGCUUUUUUU (SEQ ID NO: 65) (optionally with an inverted abasic residue at the 5′ and/or 3′ terminus).

In embodiments, the gRNA is a dgRNA and comprises or consists of:

crRNA:

mN*mN*mN*GUUUUAGAGCUAU*mG*mC*mU (SEQ ID NO: 66), where m indicates a base with 2′O-Methyl modification, * indicates a phosphorothioate bond, and N's indicate the residues of the targeting domain, e.g., as described herein, (optionally with an inverted abasic residue at the 5′ and/or 3′ terminus); and

tracr:

mA*mA*mC*AGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAAC UUGAAAAAGUGGCACCGAGUCGGUGCUUUU*mU*mU*mU (SEQ ID NO: 67), where m indicates a base with 2′O-Methyl modification, * indicates a phosphorothioate bond, and N's indicate the residues of the targeting domain (optionally with an inverted abasic residue at the 5′ and/or 3′ terminus).

In embodiments, the gRNA is a dgRNA and comprises or consists of:

crRNA:

mN*mN*mN*NNNNNNNNNNNNNNNNNGUUUAGAGCUAUGCUGUU*m U*mU*mG (SEQ ID NO: 68), where m indicates a base with 2′O-Methyl modification, * indicates a phosphorothioate bond, and N's indicate the residues of the targeting domain, e.g., as described herein, (optionally with an inverted abasic residue at the 5′ and/or 3′ terminus); and

tracr:

AACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAA AAGUGGCACCGAGUCGGUGCUUUUUUU (SEQ ID NO: 65) (optionally with an inverted abasic residue at the 5′ and/or 3′ terminus).

In embodiments, the gRNA is a dgRNA and comprises or consists of:

crRNA:

mN*mN*mN*NNNNNNNNNNNNNNNNNGUUUUAGAGCUAUGCUGUU*m U*mU*mG (SEQ ID NO: 68), where m indicates a base with 2′O-Methyl modification, * indicates a phosphorothioate bond, and N's indicate the residues of the targeting domain, e.g., as described herein, (optionally with an inverted abasic residue at the 5′ and/or 3′ terminus); and

tracr:

mA*mA*mC*AGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAAC UUGAAAAAGUGGCACCGAGUCGGUGCUUUU*mU*mU*mU (SEQ ID NO: 67), where m indicates a base with 2′O-Methyl modification, and * indicates a phosphorothioate bond (optionally with an inverted abasic residue at the 5′ and/or 3′ terminus).

In embodiments, the gRNA is a sgRNA and comprises or consists of:

mN*mN*mN*NNNNNNNNNNNNNNNNNGUUUUAGAGCUAGAAAUAGCA AGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAGUGGCACCGAGUCGGU GCU*mU*mU*mU (SEQ ID NO: 69), where m indicates a base with 2′O-Methyl modification, * indicates a phosphorothioate bond, and N's indicate the residues of the targeting domain, e.g., as described herein, (optionally with an inverted abasic residue at the 5′ and/or 3′ terminus).

In embodiments, the gRNA is a sgRNA and comprises or consists of:

mN*mN*mN*GUUUUAGAGCUAGAAAUAGCA AGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAGUGGCACCGAGUCGGU GCmU*mU*mU*U (SEQ ID NO: 70, where m indicates a base with 2′O-Methyl modification, * indicates a phosphorothioate bond, and N's indicate the residues of the targeting domain, e.g., as described herein, (optionally with an inverted abasic residue at the 5′ and/or 3′ terminus).

›DETAILED DESCRIPTION · 9 of 9

6) First Tracr Extension

Where the gRNA comprises a first flagpole extension, the tracr may comprise a first tracr extension. The first tracr extension may comprise nucleotides that are complementary, e.g., 80%, 85%, 90%, 95% or 99%, e.g., fully complementary to nucleotides of the first flagpole extension. In some aspects, the first tracr extension nucleotides that hybridize with complementary nucleotides of the first flagpole extension are contiguous. In some aspects, the first tracr extension nucleotides that hybridize with complementary nucleotides of the first flagpole extension are discontinuous, e.g., comprises two or more regions of hybridization separated by nucleotides that do not base pair with nucleotides of the first flagpole extension. In some aspects, the first tracr extension comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more nucleotides. In some aspects, the first tracr extension comprises SEQ ID NO: 56. In some aspects the first tracr extension comprises nucleic acid that is at least 80%, 85%, 90%, 95% or 99% homology to SEQ ID NO: 56.

Some or all of the nucleotides of the first tracr extension can have a modification, e.g., modification found in Section XIII herein.

In some embodiments, the sgRNA may comprise, from 5′ to 3′ and disposed 3′ to the targeting domain:

a)

(SEQ ID NO: 71)

›GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACU

UGAAAAAGUGGCACCGAGUCGGUGC;

b)

(SEQ ID NO: 72)

›GUUUAAGAGCUAGAAAUAGCAAGUUUAAAUAAGGCUAGUCCGUUAUCAACU

UGAAAAAGUGGCACCGAGUCGGUGC;

c)

(SEQ ID NO: 73)

›GUUUUAGAGCUAUGCUGGAAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCC

GUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGC;

d)

(SEQ ID NO: 74)

›GUUUAAGAGCUAUGCUGGAAACAGCAUAGCAAGUUUAAAUAAGGCUAGUCC

GUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGC;

e) any of a) to d), above, further comprising, at the 3′ end, at least 1, 2, 3, 4, 5, 6 or 7 uracil (U) nucleotides, e.g., 1, 2, 3, 4, 5, 6, or 7 uracil (U) nucleotides;

f) any of a) to d), above, further comprising, at the 3′ end, at least 1, 2, 3, 4, 5, 6 or 7 adenine (A) nucleotides, e.g., 1, 2, 3, 4, 5, 6, or 7 adenine (A) nucleotides; or

g) any of a) to f), above, further comprising, at the 5′ end (e.g., at the 5′ terminus, e.g., 5′ to the targeting domain), at least 1, 2, 3, 4, 5, 6 or 7 adenine (A) nucleotides, e.g., 1, 2, 3, 4, 5, 6, or 7 adenine (A) nucleotides.

In an embodiment, a sgRNA of the disclosure comprises or consists of, from 5′ to 3′: [targeting domain]-GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUG AAAAAGUGGCACCGAGUCGGUGCUUUU (SEQ ID NO: 75).

In an embodiment, a sgRNA of the disclosure comprises or consists of, from 5′ to 3′: [targeting domain]-GUUUAAGAGCUAUGCUGGAAACAGCAUAGCAAGUUUAAAUAAGGCUAGUCCGU UAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCUUUU (SEQ ID NO: 76).

In embodiments, any of a) to g) above is disposed directly 3′ to the targeting domain.

In some embodiments, the dgRNA may comprise:

A crRNA comprising, from 5′ to 3′, preferably disposed directly 3′ to the targeting domain:

In an embodiment, the sequence of k), above comprises the 3′ sequence UUUUUU, e.g., if a U6 promoter is used for transcription. In an embodiment, the sequence of k), above, comprises the 3′ sequence UUUU, e.g., if an HI promoter is used for transcription. In an embodiment, sequence of k), above, comprises variable numbers of 3′ U's depending, e.g., on the termination signal of the pol-III promoter used. In an embodiment, the sequence of k), above, comprises variable 3′ sequence derived from the DNA template if a T7 promoter is used. In an embodiment, the sequence of k), above, comprises variable 3′ sequence derived from the DNA template, e.g., if in vitro transcription is used to generate the RNA molecule. In an embodiment, the sequence of k), above, comprises variable 3′ sequence derived from the DNA template, e.g., if a pol-II promoter is used to drive transcription.

In an embodiment, the crRNA comprises SEQ ID NO: 79 and the tracr comprises or consists of

(SEQ ID NO: 65)

›AACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGU

GGCACCGAGUCGGUGCUUUUUUU.

In an embodiment, the crRNA comprises SEQ ID NO: 80 and the tracr comprises or consists of,

(SEQ ID NO: 84)

›AACAGCAUAGCAAGUUUAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGU

GGCACCGAGUCGGUGCUUUUUUU.

In an embodiment, the crRNA comprises or consists of, a targeting domain and, disposed 3′ to the targeting domain (e.g., disposed directly 3′ to the targeting domain), a sequence comprising, e.g., consisting of, GUUUUAGAGCUAUGCU (SEQ ID NO: 81), and the tracr comprises or consists of,

(SEQ ID NO: 76)

›GUUUAAGAGCUAUGCUGGAAACAGCAUAGCAAGUUUAAAUAAGGCUAGUCC

GUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCUUUU.

In an embodiment, the crRNA comprises or consists of, a targeting domain and, disposed 3′ to the targeting domain (e.g., disposed directly 3′ to the targeting domain), a sequence comprising, e.g., consisting of, GUUUUAGAGCUAUGCU (SEQ ID NO: 81), and the tracr comprises or consists of,

(SEQ ID NO: 85)

›AGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGC

ACCGAGUCGGUGCUUU.

In an embodiment, the crRNA comprises or consists of, a targeting domain and, disposed 3′ to the targeting domain (e.g., disposed directly 3′ to the targeting domain), a sequence comprising, e.g., consisting of, GUUUUAGAGCUAUGCUGUUUUG (SEQ ID NO: 79), and the tracr comprises or consists of,

(SEQ ID NO: 86)

›GUUGGAACCAUUCAAAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUA · 1 of 12

UCAACUUGAAAAAGUGGCACCGAGUCGGUGCUUU.

Targeting Domains Useful for gRNA molecules and other aspects of the disclosure.

Provided in the tables below are targeting domains for gRNA molecules for use in the CRISPR systems, cells, compositions and methods of the present disclosure, for example, in reducing or eliminating the expression and/or function of TET2 and/or insertion of heterologous nucleic acid sequence (e.g., nucleic acid sequence encoding a CAR, e.g., as described herein) at or near a target sequence of TET2, e.g., of a TET2 intron or intron-exon junction.

In preferred embodiments, the gRNA molecule targets a sequence in the intron between exon 9 and exon 10, or targets an intron-exon junction which introduces a break in the DNA in said intron. Examples of such gRNA molecules are gRNA molecules comprising, e.g., consisting of, a targeting domain of any one of SEQ ID NO: 10102 to SEQ ID NO: 10324. Particularly preferred gRNA molecules are gRNA molecules comprising, e.g., consisting of, a targeting domain shown in Table 2.

Particularly preferred gRNA molecules are gRNA molecules comprising, e.g., consisting of a targeting domain sequence of any one of SEQ ID NO: 10148, SEQ ID NO: 10184, SEQ ID NO: 10185, SEQ ID NO: 10188, SEQ ID NO: 10209, SEQ ID NO: 10212, SEQ ID NO: 10317, SEQ ID NO: 10318, SEQ ID NO: 10187, SEQ ID NO: 10224, SEQ ID NO: 10292, SEQ ID NO: 10149, SEQ ID NO: 10177, SEQ ID NO: 10151, SEQ ID NO: 10225 or SEQ ID NO: 10509.

In some embodiments, preferred gRNA molecules are gRNA molecules comprising or consisting of a targeting domain sequence of SEQ ID NO: 10148, 10149, 10206, 10191, 10515, 10203, 10259, 10136, 10314, 10234, 10290, 10233, 10209, 10224, 10212, 10317, 10318, 10225, 10184, 10185, 10188, 10187, 10292, 10151, 10509, 10281, 10299, 10301, or 10177.

In some embodiments, preferred gRNA molecules are gRNA molecules comprising or consisting of a targeting domain sequence of SEQ ID NO: 10148, 10149, 10290, 10209, 10224, 10212, 10317, 10318, 10225, 10184, 10185, 10188, 10187, 10292, 10151, 10509, 10281, or 10177.

In some embodiments, preferred gRNA molecules are gRNA molecules comprising or consisting of a targeting domain sequence of SEQ ID NO: 10206, 10191, 10515, 10203, 10259, 10136, 10314, or 10234.

In some embodiments, preferred gRNA molecules are gRNA molecules comprising or consisting of a targeting domain sequence of SEQ ID NO: 10191, 10203, 10259, 10136, 10314, or 10234.

In some embodiments, preferred gRNA molecules are gRNA molecules comprising or consisting of a targeting domain sequence of SEQ ID NO: 10148, 10149, or 10206. In some embodiments, preferred gRNA molecules are gRNA molecules comprising or consisting of a targeting domain sequence of SEQ ID NO: 10148. In some embodiments, preferred gRNA molecules are gRNA molecules comprising or consisting of a targeting domain sequence of SEQ ID NO: 10149. In some embodiments, preferred gRNA molecules are gRNA molecules comprising or consisting of a targeting domain sequence of SEQ ID NO: 10206.

In an aspect, the disclosure further provides for compositions useful for directing gene editing systems, e.g., a CRISPR system, zinc finger nuclease system, TALEN system, or meganuclease system, to a target sequence of a TET2 intron or TET2 intron-exon junction. In embodiments, the gene editing system further comprises a template nucleic acid, for example, for insertion of heterologous nucleic acid sequence (e.g., sequence encoding a CAR, e.g., as described herein) at or near the target locus. In an aspect, the gene editing system is a CRISPR system comprising a gRNA molecule comprising a targeting domain sequence complementary to a target sequence of a TET2 intron or TET2 intron-exon junction. In embodiments involving a CRISPR system, the gRNA molecule comprises a targeting domain sequence complementary to a target sequence adjacent to a PAM recognition sequence of the Cas molecule (e.g., Cas9 molecule) of the CRISPR system. Table 3 provides the genomic locations of the human TET2 introns according to hg38. In an aspect, the gene editing system, e.g., CRISPR system, creates a break (e.g., single or double-strand break) at a sequence (e.g., between two nucleotides) between the start nucleotide and the end nucleotide of an intron listed in Table 3. In one preferred aspect, the gene editing system, e.g., CRISPR system, creates a break (e.g., single or double-strand break) at a sequence (e.g., between two nucleotides) between the start nucleotide and the end nucleotide of the intron between exon 9 and exon 10 of Table 3 (e.g., at a position between ch4:105269748 and ch4:105272563 according to hg38).

III. Methods for Designing gRNAs

Methods for designing gRNAs are described herein, including methods for selecting, designing and validating target sequences. Exemplary targeting domains are also provided herein. Targeting Domains discussed herein can be incorporated into the gRNAs described herein.

Methods for selection and validation of target sequences as well as off-target analyses are described, e.g., in. Mali el al., 2013 SCIENCE 339(6121): 823-826; Hsu et al., 2013 NAT BIOTECHNOL, 31 (9): 827-32; Fu et al., 2014 NAT BIOTECHNOL, doi: 10.1038/nbt.2808. PubMed PM ID: 24463574; Heigwer et al., 2014 NAT METHODS 11 (2): 122-3. doi: 10.1038/nmeth.2812. PubMed PMID: 24481216; Bae el al, 2014 BIOINFORMATICS PubMed PMID: 24463181; Xiao A el al, 2014 BIOINFORMATICS PubMed PMID: 24389662.

For example, a software tool can be used to optimize the choice of gRNA within a user's target sequence, e.g., to minimize total off-target activity across the genome. Off target activity may be other than cleavage. For each possible gRNA choice e.g., using S. pyogenes Cas9, the tool can identify all off-target sequences (e.g., preceding either NAG or NGG PAMs) across the genome that contain up to certain number (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) of mismatched base-pairs. The cleavage efficiency at each off-target sequence can be predicted, e.g., using an experimentally-derived weighting scheme. Each possible gRNA is then ranked according to its total predicted off-target cleavage; the top-ranked gRNAs represent those that are likely to have the greatest on-target and the least off-target cleavage. Other functions, e.g., automated reagent design for CRISPR construction, primer design for the on-target Surveyor assay, and primer design for high-throughput detection and quantification of off-target cleavage via next-gen sequencing, can also be included in the tool. Candidate gRNA molecules can be evaluated by art-known methods or as described herein.

›GUUGGAACCAUUCAAAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUA · 2 of 12

Although software algorithms may be used to generate an initial list of potential gRNA molecules, cutting efficiency and specificity will not necessarily reflect the predicted values, and gRNA molecules typically require screening in specific cell lines, e.g., primary human cell lines, e.g., primary human immune effector cells, e.g., primary human T cells, to determine, for example, cutting efficiency, indel formation, cutting specificity and change in desired phenotype. These properties may be assayed by the methods described herein.

IV. Cas Molecules

In some embodiments, the Cas molecule is a Class 1 Cas nuclease. In some embodiments, the Cas molecule is a Class 2 Cas nuclease. See, e.g., Makarova et al. (2015), Nat Rev Microbiol, 13(11): 722-36; Shmakov et al. (2015), Molecular Cell, 60:385-397. A Class 2 Cas molecule may be a single-protein endonuclease. In some embodiments, the Class 2 Cas molecule is from a Type II, V, or VI CRISPR/Cas system and may be a single-protein endonuclease. Non-limiting examples of Class 2 Cas molecules include Cas9, Cpf1, C2c1, C2c2, and C2c3 proteins. See, e.g., Yang et al. (2016), Cell, 167(7): 1814-28; Zetsche et al. (2015), Cell, 163: 1-13. In some embodiments, the Cas molecule is a Cpf1 molecule. Cpf1 may be homologous to Cas9 and contain a RuvC-like nuclease domain. See, e.g., Zetsche et al. (2015), the Cpf1 sequences of which are incorporated by reference in their entirety.

Cas9 Molecules

In some embodiments, the Cas molecule is a Cas9 molecule or fragment or variant, e.g., catalytic or non-catalytic variant, thereof. Cas9 molecules of a variety of species can be used in the methods and compositions described herein. While the S. pyogenes Cas9 molecule are the subject of much of the disclosure herein, Cas9 molecules of, derived from, or based on the Cas9 proteins of other species listed herein can be used as well. In other words, other Cas9 molecules, e.g., S. thermophilus, Staphylococcus aureus and/or Neisseria meningitidis Cas9 molecules, may be used in the systems, methods and compositions described herein.

In some embodiments, the Cas9 molecule is a high-fidelity variant harboring alterations designed to reduce non-specific DNA contacts. See, e.g., Kleinstiver et al. (2016), Nature 529(7587): 490-95; Slaymaker et al. (2016), Science, 351(6268): 84-88; Tsai et al. (2014), Nat. Biotech. 32:569-577. In some embodiments, the high-fidelity Cas9 retains on-target activities comparable to wild-type Cas9. In some embodiments, the high-fidelity Cas9 reduces off-target activities by at least about 50%, 60%, 70%, 80%, 90%, 95%, or 99% as compared to wild-type Cas9, e.g., as measured by genome-wide break capture and targeted sequencing methods. In some embodiments, the high-fidelity Cas9 renders off-target activities undetectable, e.g., as measured by genome-wide break capture and targeted sequencing methods. In some embodiments, the high-fidelity Cas9 is Streptococcus pyogenes SpCas9-HF 1 (Kleinstiver 2016) or Alt-R® S.p. HiFi Cas9 Nuclease 3NLS (IDT).

Additional Cas9 species include: Acidovorax avenae, Actinobacillus pleuropneumoniae, Actinobacillus succinogenes, Actinobacillus suis, Actinomyces sp., Cycliphilus denitrificans, Aminomonas paucivorans, Bacillus cereus, Bacillus smithii, Bacillus thuringiensis, Bacteroides sp., Blastopirellula marina, Bradyrhiz' obium sp., Brevibacillus latemsporus, Campylobacter coli, Campylobacter jejuni, Campylobacter lad, Candidatus Puniceispirillum, Clostridiu cellulolyticum, Clostridium perfringens, Corynebacterium accolens, Corynebacterium diphtheria, Corynebacterium matruchotii, Dinoroseobacter sliibae, Eubacterium dolichum, gamma proteobacterium, Gluconacetobacler diazotrophicus, Haemophilus parainfluenzae, Haemophilus sputorum, Helicobacter canadensis, Helicobacter cinaedi, Helicobacter mustelae, Ilyobacler polytropus, Kingella kingae, Lactobacillus crispatus, Listeria ivanovii, Listeria monocytogenes, Listeriaceae bacterium, Methylocystis sp., Methylosinus trichosporium, Mobiluncus mulieris, Neisseria bacilliformis, Neisseria cinerea, Neisseria flavescens, Neisseria lactamica. Neisseria sp., Neisseria wadsworthii, Nitrosomonas sp., Parvibaculum lavamentivorans, Pasteurella multocida, Phascolarctobacterium succinatutens, Ralstonia syzygii, Rhodopseudomonas palustris, Rhodovulum sp., Simonsiella muelleri, Sphingomonas sp., Sporolactobacillus vineae, Staphylococcus lugdunensis, Streptococcus sp., Subdoligranulum sp., Tislrella mobilis, Treponema sp., or Verminephrobacter eiseniae.

A Cas9 molecule, as that term is used herein, refers to a molecule that can interact with a gRNA molecule (e.g., sequence of a domain of a tracr) and, in concert with the gRNA molecule, localize (e.g., target or home) to a site which comprises a target sequence and PAM sequence.

In an embodiment, the Cas9 molecule is capable of cleaving a target nucleic acid molecule, which may be referred to herein as an active Cas9 molecule. In an embodiment, an active Cas9 molecule, comprises one or more of the following activities: a nickase activity, i.e., the ability to cleave a single strand, e.g., the non-complementary strand or the complementary strand, of a nucleic acid molecule; a double stranded nuclease activity, i.e., the ability to cleave both strands of a double stranded nucleic acid and create a double stranded break, which in an embodiment is the presence of two nickase activities; an endonuclease activity; an exonuclease activity; and a helicase activity, i.e., the ability to unwind the helical structure of a double stranded nucleic acid.

In an embodiment, an enzymatically active Cas9 molecule cleaves both DNA strands and results in a double stranded break. In an embodiment, a Cas9 molecule cleaves only one strand, e.g., the strand to which the gRNA hybridizes to, or the strand complementary to the strand the gRNA hybridizes with. In an embodiment, an active Cas9 molecule comprises cleavage activity associated with an HNH-like domain. In an embodiment, an active Cas9 molecule comprises cleavage activity associated with an N-terminal RuvC-like domain. In an embodiment, an active Cas9 molecule comprises cleavage activity associated with an HNH-like domain and cleavage activity associated with an N-terminal RuvC-like domain. In an embodiment, an active Cas9 molecule comprises an active, or cleavage competent, HNH-like domain and an inactive, or cleavage incompetent, N-terminal RuvC-like domain. In an embodiment, an active Cas9 molecule comprises an inactive, or cleavage incompetent, HNH-like domain and an active, or cleavage competent, N-terminal RuvC-like domain.

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In an embodiment, the ability of an active Cas9 molecule to interact with and cleave a target nucleic acid is PAM sequence dependent. A PAM sequence is a sequence in the target nucleic acid. In an embodiment, cleavage of the target nucleic acid occurs upstream from the PAM sequence. Active Cas9 molecules from different bacterial species can recognize different sequence motifs (e.g., PAM sequences). In an embodiment, an active Cas9 molecule of S. pyogenes recognizes the sequence motif NGG and directs cleavage of a target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from that sequence. See, e.g., Mali el al., SCIENCE 2013; 339(6121): 823-826. In an embodiment, an active Cas9 molecule of S. thermophilus recognizes the sequence motif NGGNG and NNAGAAW (W=A or T) and directs cleavage of a core target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from these sequences. See, e.g., Horvath et al., SCIENCE 2010; 327(5962): 167-170, and Deveau et al, J BACTERIOL 2008; 190(4): 1390-1400. In an embodiment, an active Cas9 molecule of S. mutans recognizes the sequence motif NGG or NAAR (R-A or G) and directs cleavage of a core target nucleic acid sequence 1 to 10, e.g., 3 to 5 base pairs, upstream from this sequence. See, e.g., Deveau et al., J BACTERIOL 2008; 190(4): 1390-1400.

In an embodiment, an active Cas9 molecule of S. aureus recognizes the sequence motif NNGRR (R=A or G) and directs cleavage of a target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from that sequence. See, e.g., Ran F. et al., NATURE, vol. 520, 2015, pp. 186-191. In an embodiment, an active Cas9 molecule of N. meningitidis recognizes the sequence motif NNNNGATT and directs cleavage of a target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from that sequence. See, e.g., Hou et al., 110(39): 15644-49 (2013). The ability of a Cas9 molecule to recognize a PAM sequence can be determined, e.g., using a transformation assay described in Jinek et al, SCIENCE 2012, 337:816.

Some Cas9 molecules have the ability to interact with a gRNA molecule, and in conjunction with the gRNA molecule bind to (e.g., target or localize to) a core target domain, but are incapable of cleaving the target nucleic acid, or incapable of cleaving at efficient rates. Cas9 molecules having no, or no substantial, cleavage activity may be referred to herein as an inactive Cas9 (an enzymatically inactive Cas9), a dead Cas9, or a dCas9 molecule. See, e.g., Gilbert et al. (2013), Cell, 154(2): 442-51. For example, an inactive Cas9 molecule can lack cleavage activity or have substantially less, e.g., less than 20, 10, 5, 1 or 0.1% of the cleavage activity of a reference Cas9 molecule, as measured by an assay described herein.

Other Cas molecules, e.g., Cpf1, may also have the ability to interact with a gRNA molecule, and in conjunction with the gRNA molecule bind to (e.g., target or localize to) a core target domain, but may be incapable of cleaving the target nucleic acid, or incapable of cleaving at efficient rates. See, e.g., WO2016/205711A1, incorporated herein by reference. Cpf1 molecules having no, or no substantial, cleavage activity may be referred to herein as an inactive Cpf1 (an enzymatically inactive Cpf1), a dead Cpf1, a dCpf1, a DNase-dead Cpf1, or a ddCpf1 molecule. See, e.g., Zhang et al. (2017), Cell Discov. 3:17018. For example, a ddCpf1 molecule can lack cleavage activity, DNase activity, or have substantially less, e.g., less than 20, 10, 5, 1 or 0.1% of the cleavage activity of a reference Cpf1 molecule, as measured by an assay described herein.

Exemplary naturally occurring Cas9 molecules that may be used with the methods described herein are described in Chylinski et al, RNA Biology 2013; 10:5, 727-737. Such Cas9 molecules include Cas9 molecules of a cluster 1 bacterial family, cluster 2 bacterial family, cluster 3 bacterial family, cluster 4 bacterial family, cluster 5 bacterial family, cluster 6 bacterial family, a cluster 7 bacterial family, a cluster 8 bacterial family, a cluster 9 bacterial family, a cluster 10 bacterial family, a cluster 1 1 bacterial family, a cluster 12 bacterial family, a cluster 13 bacterial family, a cluster 14 bacterial family, a cluster 1 bacterial family, a cluster 16 bacterial family, a cluster 17 bacterial family, a cluster 1 8 bacterial family, a cluster 19 bacterial family, a cluster 20 bacterial family, a cluster 21 bacterial family, a cluster 22 bacterial family, a cluster 23 bacterial family, a cluster 24 bacterial family, a cluster 25 bacterial family, a cluster 26 bacterial family, a cluster 27 bacterial family, a cluster 28 bacterial family, a cluster 29 bacterial family, a cluster 30 bacterial family, a cluster 31 bacterial family, a cluster 32 bacterial family, a cluster 33 bacterial family, a cluster 34 bacterial family, a cluster 35 bacterial family, a cluster 36 bacterial family, a cluster 37 bacterial family, a cluster 38 bacterial family, a cluster 39 bacterial family, a cluster 40 bacterial family, a cluster 41 bacterial family, a cluster 42 bacterial family, a cluster 43 bacterial family, a cluster 44 bacterial family, a cluster 45 bacterial family, a cluster 46 bacterial family, a cluster 47 bacterial family, a cluster 48 bacterial family, a cluster 49 bacterial family, a cluster 50 bacterial family, a cluster 5 1 bacterial family, a cluster 52 bacterial family, a cluster 53 bacterial family, a cluster 54 bacterial family, a cluster 55 bacterial family, a cluster 56 bacterial family, a cluster 57 bacterial family, a cluster 58 bacterial family, a cluster 59 bacterial family, a cluster 60 bacterial family, a cluster 61 bacterial family, a cluster 62 bacterial family, a cluster 63 bacterial family, a cluster 64 bacterial family, a cluster 65 bacterial family, a cluster 66 bacterial family, a cluster 67 bacterial family, a cluster 68 bacterial family, a cluster 69 bacterial family, a cluster 70 bacterial family, a cluster 71 bacterial family, a cluster 72 bacterial family, a cluster 73 bacterial family, a cluster 74 bacterial family, a cluster 75 bacterial family, a cluster 76 bacterial family, a cluster 77 bacterial family, or a cluster 78 bacterial family.

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Exemplary naturally occurring Cas9 molecules include a Cas9 molecule of a cluster 1 bacterial family. Examples include a Cas9 molecule of: S. pyogenes (e.g., strain SF370, MGAS 10270, MGAS 10750, MGAS2096, MGAS315, MGAS5005, MGAS6180, MGAS9429, NZ131 and SSI-1), S. thermophilus (e.g., strain LMD-9), S. pseudoporcinus (e.g., strain SPIN 20026), S. mutans (e.g., strain UA 159, NN2025), S. macacae (e.g., strain NCTC1 1558), S. gallolylicus (e.g., strain UCN34, ATCC BAA-2069), S. equines (e.g., strain ATCC 9812, MGCS 124), S. dysdalactiae (e.g., strain GGS 124), S. bovis (e.g., strain ATCC 700338), S. anginosus (e.g.; strain F0211), S. agalactia (e.g., strain NEM316, A909), Listeria monocytogenes (e.g., strain F6854), Listeria innocua ( L. innocua , e.g., strain Clip 1 1262), EtUerococcus italicus (e.g., strain DSM 15952), or Enterococcus faecium (e.g., strain 1,231, 408). Additional exemplary Cas9 molecules are a Cas9 molecule of Neisseria meningitidis (Hou et al. 110(39): 15644-49 (2013)) and a S. aureus Cas9 molecule.

In an embodiment, a Cas9 molecule, e.g., an active Cas9 molecule or inactive Cas9 molecule, comprises an amino acid sequence: having 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% homology with; differs at no more than 1%, 2%, 5%, 10%, 15%, 20%, 30%, or 40% of the amino acid residues when compared with; differs by at least 1, 2, 5, 10 or 20 amino acids but by no more than 100, 80, 70, 60, 50, 40 or 30 amino acids from; or is identical to; any Cas9 molecule sequence described herein or a naturally occurring Cas9 molecule sequence, e.g., a Cas9 molecule from a species listed herein or described in Chylinski et al., RNA Biology 2013, 10:5,′I2′-T, 1 Hou et al. 110(39): 15644-49 (2013).

In an embodiment, a Cas9 molecule comprises an amino acid sequence having 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% homology with; differs at no more than 1%, 2%, 5%, 10%, 15%, 20%, 30%, or 40% of the amino acid residues when compared with; differs by at least 1, 2, 5, 10 or 20 amino acids but by no more than 100, 80, 70, 60, 50, 40 or 30 amino acids from; or is identical to; S. pyogenes Cas9:

In embodiments, the Cas9 molecule is a S. pyogenes Cas9 variant of SEQ ID NO: 90 that includes one or more mutations to positively charged amino acids (e.g., lysine, arginine or histidine) that introduce an uncharged or nonpolar amino acid, e.g., alanine, at said position. In embodiments, the mutation is to one or more positively charged amino acids in the nt-groove of Cas9. In embodiments, the Cas9 molecule is a S. pyogenes Cas9 variant of SEQ ID NO: 90 that includes a mutation at position 855 of SEQ ID NO: 90, for example a mutation to an uncharged amino acid, e.g., alanine, at position 855 of SEQ ID NO: 90. In embodiments, the Cas9 molecule has a mutation only at position 855 of SEQ ID NO: 90, relative to SEQ ID NO: 90, e.g., to an uncharged amino acid, e.g., alanine. In embodiments, the Cas9 molecule is a S. pyogenes Cas9 variant of SEQ ID NO: 90 that includes a mutation at position 810, a mutation at position 1003, and/or a mutation at position 1060 of SEQ ID NO: 90, for example a mutation to alanine at position 810, position 1003, and/or position 1060 of SEQ ID NO: 90. In embodiments, the Cas9 molecule has a mutation only at position 810, position 1003, and position 1060 of SEQ ID NO: 90, relative to SEQ ID NO: 90, e.g., where each mutation is to an uncharged amino acid, for example, alanine. In embodiments, the Cas9 molecule is a S. pyogenes Cas9 variant of SEQ ID NO: 90 that includes a mutation at position 848, a mutation at position 1003, and/or a mutation at position 1060 of SEQ ID NO: 90, for example a mutation to alanine at position 848, position 1003, and/or position 1060 of SEQ ID NO: 90. In embodiments, the Cas9 molecule has a mutation only at position 848, position 1003, and position 1060 of SEQ ID NO: 90, relative to SEQ ID NO: 90, e.g., where each mutation is to an uncharged amino acid, for example, alanine. In embodiments, the Cas9 molecule is a Cas9 molecule as described in Slaymaker et al., Science Express , available online Dec. 1, 2015 at Science DOI: 10.1126/science.aad5227.

In embodiments, the Cas9 molecule is a S pyogenes Cas9 variant of SEQ ID NO: 90 that includes one or more mutations. In embodiments, the Cas9 variant comprises a mutation at position 80 of SEQ ID NO: 90, e.g., includes a leucine at position 80 of SEQ ID NO: 90 (i.e., comprises or consists of, SEQ ID NO: 90 with a C80L mutation). In embodiments, the Cas9 variant comprises a mutation at position 574 of SEQ ID NO: 90, e.g., includes a glutamic acid at position 574 of SEQ ID NO: 90 (i.e., comprises or consists of, SEQ ID NO: 90 with a C574E mutation). In embodiments, the Cas9 variant comprises a mutation at position 80 and a mutation at position 574 of SEQ ID NO: 90, e.g., includes a leucine at position 80 of SEQ ID NO: 90, and a glutamic acid at position 574 of SEQ ID NO: 90 (i.e., comprises or consists of, SEQ ID NO: 90 with a C80L mutation and a C574E mutation). Without being bound by theory, it is believed that such mutations improve the solution properties of the Cas9 molecule.

In embodiments, the Cas9 molecule is a S pyogenes Cas9 variant of SEQ ID NO: 90 that includes one or more mutations. In embodiments, the Cas9 variant comprises a mutation at position 147 of SEQ ID NO: 90, e.g., includes a tyrosine at position 147 of SEQ ID NO: 90 (i.e., comprises or consists of, SEQ ID NO: 90 with a D147Y mutation). In embodiments, the Cas9 variant comprises a mutation at position 411 of SEQ ID NO: 90, e.g., includes a threonine at position 411 of SEQ ID NO: 90 (i.e., comprises or consists of, SEQ ID NO: 90 with a P411T mutation). In embodiments, the Cas9 variant comprises a mutation at position 147 and a mutation at position 411 of SEQ ID NO: 90, e.g., includes a tyrosine at position 147 of SEQ ID NO: 90, and a threonine at position 411 of SEQ ID NO: 90 (i.e., comprises or consists of, SEQ ID NO: 90 with a D147Y mutation and a P411T mutation). Without being bound by theory, it is believed that such mutations improve the targeting efficiency of the Cas9 molecule, e.g., in yeast.

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In embodiments, the Cas9 molecule is a S. pyogenes Cas9 variant of SEQ ID NO: 90 that includes one or more mutations. In embodiments, the Cas9 variant comprises a mutation at position 1135 of SEQ ID NO: 90, e.g., includes a glutamic acid at position 1135 of SEQ ID NO: 90 (i.e., comprises or consists of, SEQ ID NO: 90 with a D1135E mutation). Without being bound by theory, it is believed that such mutations improve the selectivity of the Cas9 molecule for the NGG PAM sequence versus the NAG PAM sequence.

In embodiments, the Cas9 molecule is a S. pyogenes Cas9 variant of SEQ ID NO: 90 that includes one or more mutations that introduce an uncharged or nonpolar amino acid, e.g., alanine, at certain positions. In embodiments, the Cas9 molecule is a S. pyogenes Cas9 variant of SEQ ID NO: 90 that includes a mutation at position 497, a mutation at position 661, a mutation at position 695 and/or a mutation at position 926 of SEQ ID NO: 90, for example a mutation to alanine at position 497, position 661, position 695 and/or position 926 of SEQ ID NO: 90. In embodiments, the Cas9 molecule has a mutation only at position 497, position 661, position 695, and position 926 of SEQ ID NO: 90, relative to SEQ ID NO: 90, e.g., where each mutation is to an uncharged amino acid, for example, alanine. Without being bound by theory, it is believed that such mutations reduce the cutting by the Cas9 molecule at off-target sites

It will be understood that the mutations described herein to the Cas9 molecule may be combined, and may be combined with any of the fusions or other modifications described herein, and the Cas9 molecule may be tested in any of the assays described herein.

Various types of Cas molecules can be used herein. In some embodiments, Cas molecules of Type II Cas systems are used. In other embodiments, Cas molecules of other Cas systems are used. For example, Type I or Type III Cas molecules may be used. Exemplary Cas molecules (and Cas systems) are described, e.g., in Haft et al., PLoS COMPUTATIONAL BIOLOGY 2005, 1(6): e60 and Makarova et al., NATURE REVIEW MICROBIOLOGY 2011 9:467-477, the contents of both references are incorporated herein by reference in their entirety.

In an embodiment, a Cas or Cas9 molecule used in the methods disclosed herein comprises one or more of the following activities: a nickase activity; a double stranded cleavage activity (e.g., an endonuclease and/or exonuclease activity); a helicase activity; or the ability, together with a gRNA molecule, to localize to a target nucleic acid.

Altered Cas9 Molecules

Naturally occurring Cas9 molecules may possess a number of properties, including: nickase activity, nuclease activity (e.g., endonuclease and/or exonuclease activity); helicase activity; the ability to associate functionally with a gRNA molecule; and the ability to target (or localize to) a site on a nucleic acid (e.g., PAM recognition and specificity). In an embodiment, a Cas9 molecule used with the methods disclosed herein can include all or a subset of these properties. In typical embodiments, Cas9 molecules have the ability to interact with a gRNA molecule and, in concert with the gRNA molecule, localize to a site in a nucleic acid. Other activities, e.g., PAM specificity, cleavage activity, or helicase activity can vary more widely in Cas9 molecules.

Cas9 molecules with desired properties can be made in a number of ways, e.g., by alteration of a parental, e.g., naturally occurring Cas9 molecule to provide an altered Cas9 molecule having a desired property. For example, one or more mutations or differences relative to a parental Cas9 molecule can be introduced. Such mutations and differences may comprise: substitutions (e.g., conservative substitutions or substitutions of non-essential amino acids); insertions; or deletions. In an embodiment, a Cas9 molecule can comprises one or more mutations or differences, e.g., at least 1, 2, 3, 4, 5, 10, 15, 20, 30, 40 or 50 mutations but less than 200, 100, or 80 mutations relative to a reference Cas9 molecule while retaining or enhancing one or more activities of the reference Cas9 molecule.

In an embodiment, a mutation or mutations do not have a substantial effect on a Cas9 activity, e.g. a Cas9 activity described herein. In an embodiment, a mutation or mutations have a substantial effect on a Cas9 activity, e.g. a Cas9 activity described herein. In an embodiment, exemplary activities comprise one or more of PAM specificity, cleavage activity, and helicase activity. A mutation(s) can be present, e.g., in: one or more RuvC-like domain, e.g., an N-terminal RuvC-like domain; an HNH-like domain; a region outside the RuvC-like domains and the HNH-like domain. In some embodiments, a mutation(s) is present in an N-terminal RuvC-like domain. In some embodiments, a mutation(s) is present in an HNH-like domain. In some embodiments, mutations are present in both an N-terminal RuvC-like domain and an HNH-like domain.

Whether or not a particular sequence, e.g., a substitution, may affect one or more activity, such as targeting activity, cleavage activity, etc., can be evaluated or predicted by, e.g., evaluating whether the mutation is conservative or by the method described in Section ΠI. In an embodiment, a “non-essential” amino acid residue, as used in the context of a Cas9 molecule, is a residue that can be altered from the wild-type sequence of a Cas9 molecule, e.g., a naturally occurring Cas9 molecule, e.g., an active Cas9 molecule, without abolishing or more preferably, without substantially altering a Cas9 activity (e.g., cleavage activity), whereas changing an “essential” amino acid residue results in a substantial loss of activity (e.g., cleavage activity).

Cas9 Molecules with Altered PAM Recognition or No PAM Recognition

Naturally occurring Cas9 molecules may recognize specific PAM sequences, for example the PAM recognition sequences described above for S. pyogenes, S. thermophilus, S. mutans, S. aureus and N. meningitidis.

In an embodiment, a Cas9 molecule has the same PAM specificities as a naturally occurring Cas9 molecule. In other embodiments, a Cas9 molecule has a PAM specificity not associated with a naturally occurring Cas9 molecule, or a PAM specificity not associated with the naturally occurring Cas9 molecule to which it has the closest sequence homology. For example, a naturally occurring Cas9 molecule can be altered, e.g., to alter PAM recognition, e.g., to alter the PAM sequence that the Cas9 molecule recognizes to decrease off target sites and/or improve specificity; or eliminate a PAM recognition requirement. In an embodiment, a Cas9 molecule can be altered, e.g., to increase length of PAM recognition sequence and/or improve Cas9 specificity to high level of identity to decrease off target sites and increase specificity. In an embodiment, the length of the PAM recognition sequence is at least 4, 5, 6, 7, 8, 9, 10 or 15 amino acids in length. Cas9 molecules that recognize different PAM sequences and/or have reduced off-target activity can be generated using directed evolution. Exemplary methods and systems that can be used for directed evolution of Cas9 molecules are described, e.g., in Esvelt el al, Nature 2011, 472(7344): 499-503. Candidate Cas9 molecules can be evaluated, e.g., by methods described herein.

›GUUGGAACCAUUCAAAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUA · 6 of 12

Non-Cleaving and Modified-Cleavage Cas9 Molecules

In an embodiment, a Cas9 molecule comprises a cleavage property that differs from a naturally occurring Cas9 molecule, e.g., that differs from the naturally occurring Cas9 molecule having the closest homology. For example, a Cas9 molecule can differ from naturally occurring Cas9 molecules, e.g., a Cas9 molecule of S. pyogenes , as follows: its ability to modulate, e.g., decreased or increased, cleavage of a double stranded break (endonuclease and/or exonuclease activity), e.g., as compared to a naturally occurring Cas9 molecule (e.g., a Cas9 molecule of S. pyogenes ); its ability to modulate, e.g., decreased or increased, cleavage of a single strand of a nucleic acid, e.g., a non-complementary strand of a nucleic acid molecule or a complementary strand of a nucleic acid molecule (nickase activity), e.g., as compared to a naturally occurring Cas9 molecule (e.g., a Cas9 molecule of S. pyogenes ); or the ability to cleave a nucleic acid molecule, e.g., a double stranded or single stranded nucleic acid molecule, can be eliminated.

Modified Cleavage Active Cas9 Molecules

In an embodiment, an active Cas9 molecule comprises one or more of the following activities: cleavage activity associated with an N-terminal RuvC-like domain; cleavage activity associated with an HNH-like domain; cleavage activity associated with an HNH domain and cleavage activity associated with an N-terminal RuvC-like domain.

In an embodiment, the Cas9 molecule is a Cas9 nickase, e.g., cleaves only a single strand of DNA. In some embodiments, the Cas9 nickase comprises a RuvC-like domain that is capable of cleavage and a HNH-like domain that has reduced cleavage capability or is incapable of cleavage. In alternate embodiments, the Cas9 nickase comprises a HNH-like domain that is capable of cleavage and a RuvC-like domain that has reduced cleavage capability or is incapable of cleavage. In an embodiment, the Cas9 nickase includes a mutation at position 10 and/or a mutation at position 840 of SEQ ID NO: 90, e.g., comprises a D10A and/or H840A mutation to SEQ ID NO: 90.

Non-Cleaving Inactive Cas9 Molecules

In an embodiment, the altered Cas9 molecule is an inactive Cas9 molecule which does not cleave a nucleic acid molecule (either double stranded or single stranded nucleic acid molecules) or cleaves a nucleic acid molecule with significantly less efficiency, e.g., less than 20, 10, 5, 1 or 0.1% of the cleavage activity of a reference Cas9 molecule, e.g., as measured by an assay described herein. The reference Cas9 molecule can by a naturally occurring unmodified Cas9 molecule, e.g., a naturally occurring Cas9 molecule such as a Cas9 molecule of S. pyogenes, S. thermophilus, S. aureus or N. meningitidis . In an embodiment, the reference Cas9 molecule is the naturally occurring Cas9 molecule having the closest sequence identity or homology. In an embodiment, the inactive Cas9 molecule lacks substantial cleavage activity associated with an N-terminal RuvC-like domain and cleavage activity associated with an HNH-like domain.

In an embodiment, the Cas9 molecule is dCas9. See, e.g., Tsai et al. (2014), Nat. Biotech. 32:569-577.

A catalytically inactive Cas9 molecule may be fused with a transcription repressor. An inactive Cas9 fusion protein complexes with a gRNA and localizes to a DNA sequence specified by gRNA's targeting domain, but, unlike an active Cas9, it will not cleave the target DNA. Fusion of an effector domain, such as a transcriptional repression domain, to an inactive Cas9 enables recruitment of the effector to any DNA site specified by the gRNA. Site specific targeting of a Cas9 fusion protein to a promoter region of a gene can block or affect polymerase binding to the promoter region, for example, a Cas9 fusion with a transcription factor (e.g., a transcription activator) and/or a transcriptional enhancer binding to the nucleic acid to increase or inhibit transcription activation. Alternatively, site specific targeting of a Cas9-fusion to a transcription repressor to a promoter region of a gene can be used to decrease transcription activation.

Transcription repressors or transcription repressor domains that may be fused to an inactive Cas9 molecule can include ruppel associated box (KRAB or SKD), the Mad mSIN3 interaction domain (SID) or the ERF repressor domain (ERD).

In another embodiment, an inactive Cas9 molecule may be fused with a protein that modifies chromatin. For example, an inactive Cas9 molecule may be fused to heterochromatin protein 1 (HP1), a histone lysine methyltransferase (e.g., SUV39H 1, SUV39H2, G9A, ESET/SETDB1, Pr-SET7/8, SUV4-20H 1,RIZ1), a histone lysine demethylates (e.g., LSD1/BHC1 10, SpLsdl/Sw, 1/Safl 10, Su(var)3-3, JMJD2A/JHDM3A, JMJD2B, JMJD2C/GASC1, JMJD2D, Rph 1, JARID 1 A/RBP2, JARI DIB/PLU-I, JAR1D 1C/SMCX, JARID1 D/SMCY, Lid, Jhn2, Jmj2), a histone lysine deacetylases (e.g., HDAC1, HDAC2, HDAC3, HDAC8, Rpd3, Hos 1, Cir6, HDAC4, HDAC5, HDAC7, HDAC9, Hdal, Cir3, SIRT 1, SIRT2, Sir2, Hst 1, Hst2, Hst3, Hst4, HDAC 11) and a DNA methylases (DNMT1,DNMT2a/DMNT3b, MET 1). An inactive Cas9-chromatin modifying molecule fusion protein can be used to alter chromatin status to reduce expression a target gene.

The heterologous sequence (e.g., the transcription repressor domain) may be fused to the N- or C-terminus of the inactive Cas9 protein. In an alternative embodiment, the heterologous sequence (e.g., the transcription repressor domain) may be fused to an internal portion (i.e., a portion other than the N-terminus or C-terminus) of the inactive Cas9 protein.

The ability of a Cas9 molecule/gRNA molecule complex to bind to and cleave a target nucleic acid can be evaluated, e.g., by the methods described herein in Section II. The activity of a Cas9 molecule, e.g., either an active Cas9 or an inactive Cas9, alone or in a complex with a gRNA molecule may also be evaluated by methods well-known in the art, including, gene expression assays and chromatin-based assays, e.g., chromatin immunoprecipitation (ChiP) and chromatin in vivo assay (CiA).

›GUUGGAACCAUUCAAAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUA · 7 of 12

Other Molecules

In embodiments, the Cas molecule, e.g., a Cas9 of S. pyogenes , may comprise one or more amino acid sequences that confer additional activity. Non-limiting examples include one or more of a nuclear localization signal or sequence, a mitochondrial localization signal, a chloroplast localization signal, a endoplasmic reticulum (ER) retention signal, a tag or a marker (e.g., a histidine tag or a fluorescent protein), or a larger polypeptide, e.g., an enzyme, a transcription factor, or a functional portion thereof (see, e.g., Maeder et al., 2013; Perez-Piniera et al., 2013; Gilbert et al., 2013; Guilinger et al., 2014).

In some aspects, the Cas9 molecule may comprise one or more nuclear localization sequences (NLSs), such as at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more NLSs. In some embodiments, the Cas9 molecule comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more NLSs at or near the amino-terminus, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more NLSs at or near the carboxy-terminus, or a combination of these (e.g. one or more NLS at the amino-terminus and one or more NLS at the carboxy terminus). When more than one NLS is present, each may be selected independently of the others, such that a single NLS may be present in more than one copy and/or in combination with one or more other NLSs present in one or more copies. In some embodiments, an NLS is considered near the N- or C-terminus when the nearest amino acid of the NLS is within about 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 40, 50, or more amino acids along the polypeptide chain from the N- or C-terminus. Typically, an NLS consists of one or more short sequences of positively charged lysines or arginines exposed on the protein surface, but other types of NLS are known. Non-limiting examples of NLSs include an NLS sequence comprising or derived from: the NLS of the SV40 virus large T-antigen, having the amino acid sequence PKKKRKV (SEQ ID NO: 91); the NLS from nucleoplasmin (e.g. the nucleoplasmin bipartite NLS with the sequence KRPAATKKAGQAKKKK (SEQ ID NO: 92); the c-myc NLS having the amino acid sequence PAAKRVKLD (SEQ ID NO: 93) or RQRRNELKRSP (SEQ ID NO: 94); the hRNPA1 M9 NLS having the sequence NQSSNFGPMKGGNFGGRSSGPYGGGGQYFAKPRNQGGY (SEQ ID NO: 95); the sequence RMRIZFKNKGKDTAELRRRRVEVSVELRKAKKDEQILKRRNV (SEQ ID NO: 96) of the IBB domain from importin-alpha; the sequences VSRKRPRP (SEQ ID NO: 97) and PPKKARED (SEQ ID NO: 98) of the myoma T protein; the sequence PQPKKKPL (SEQ ID NO: 99) of human p53; the sequence SALIKKKKKMAP (SEQ ID NO: 100) of mouse c-ab1 IV; the sequences DRLRR (SEQ ID NO: 101) and PKQKKRK (SEQ ID NO: 102) of the influenza virus NS1; the sequence RKLKKKIKKL (SEQ ID NO: 103) of the Hepatitis virus delta antigen; the sequence REKKKFLKRR (SEQ ID NO: 104) of the mouse Mxl protein; the sequence KRKGDEVDGVDEVAKKKSKK (SEQ ID NO: 105) of the human poly(ADP-ribose) polymerase; and the sequence RKCLQAGMNLEARKTKK (SEQ ID NO: 106) of the steroid hormone receptors (human) glucocorticoid. Other suitable NLS sequences are known in the art (e.g., Sorokin, Biochemistry (Moscow) (2007) 72:13, 1439-1457; Lange J Biol Chem. (2007) 282:8, 5101-5).

In some aspects, the Cas9 molecule may comprise one or more amino acid sequences that allow the Cas9 molecule to be specifically recognized, for example a tag. In one embodiment, the tag is a Histidine tag, e.g., a histidine tag comprising at least 3, 4, 5, 6, 7, 8, 9, 10 or more histidine amino acids (SEQ ID NO: 107). In embodiments, the histidine tag is a His6 tag (six histidines) (SEQ ID NO: 108). In other embodiments, the histidine tag is a His8 tag (eight histidines) (SEQ ID NO: 109). In embodiments, the histidine tag may be separated from one or more other portions of the Cas9 molecule by a linker. In embodiments, the linker is GGS or a repeat of two or more GGS sequences. An example of such a fusion is the Cas9 molecule iProt106520.

In some aspects, the Cas9 molecule may comprise one or more amino acid sequences that are recognized by a protease (e.g., comprise a protease cleavage site). In embodiments, the cleavage site is the tobacco etch virus (TEV) cleavage site, e.g., comprises the sequence ENLYFQG (SEQ ID NO: 110). In some aspects the protease cleavage site, e.g., the TEV cleavage site is disposed between a tag, e.g., a His tag, e.g., a His6 (SEQ ID NO: 108) or His8 tag (SEQ ID NO: 109), and the remainder of the Cas9 molecule. Without being bound by theory it is believed that such introduction will allow for the use of the tag for, e.g., purification of the Cas9 molecule, and then subsequent cleavage so the tag does not interfere with the Cas9 molecule function.

In embodiments, the Cas9 molecule (e.g., a Cas9 molecule as described herein) comprises an N-terminal NLS, and a C-terminal NLS (e.g., comprises, from N- to C-terminal NLS-Cas9-NLS), e.g., wherein each NLS is an SV40 NLS (PKKKRKV (SEQ ID NO: 91)). In embodiments, the Cas9 molecule (e.g., a Cas9 molecule as described herein) comprises an N-terminal NLS, a C-terminal NLS, and a C-terminal His6 tag (SEQ ID NO: 108) (e.g., comprises, from N- to C-terminal NLS-Cas9-NLS-His tag), e.g., wherein each NLS is an SV40 NLS (PKKKRKV (SEQ ID NO: 91)). In embodiments, the Cas9 molecule (e.g., a Cas9 molecule as described herein) comprises an N-terminal His tag (e.g., His6 tag (SEQ ID NO: 108)), an N-terminal NLS, and a C-terminal NLS (e.g., comprises, from N- to C-terminal His tag-NLS-Cas9-NLS), e.g., wherein each NLS is an SV40 NLS (PKKKRKV (SEQ ID NO: 91)). In embodiments, the Cas9 molecule (e.g., a Cas9 molecule as described herein) comprises an N-terminal NLS and a C-terminal His tag (e.g., His6 tag (SEQ ID NO: 108)) (e.g., comprises from N- to C-terminal His tag-Cas9-NLS), e.g., wherein the NLS is an SV40 NLS (PKKKRKV (SEQ ID NO: 91)). In embodiments, the Cas9 molecule (e.g., a Cas9 molecule as described herein) comprises an N-terminal His tag (e.g., His6 tag (SEQ ID NO: 108)) and a C-terminal NLS (e.g., comprises from N- to C-terminal NLS-Cas9-His tag), e.g., wherein the NLS is an SV40 NLS (PKKKRKV (SEQ ID NO: 91)). In embodiments, the Cas9 molecule (e.g., a Cas9 molecule as described herein) comprises an N-terminal His tag (e.g., His8 tag (SEQ ID NO: 109)), an N-terminal cleavage domain (e.g., a tobacco etch virus (TEV) cleavage domain (e.g., comprises the sequence ENLYFQG (SEQ ID NO: 110))), an N-terminal NLS (e.g., an SV40 NLS; SEQ ID NO: 91), and a C-terminal NLS (e.g., an SV40 NLS; SEQ ID NO: 91) (e.g., comprises from N- to C-terminal His tag-TEV-NLS-Cas9-NLS). In any of the aforementioned embodiments the Cas9 has the sequence of SEQ ID NO: 90. Alternatively, in any of the aforementioned embodiments, the Cas9 has a sequence of a Cas9 variant of SEQ ID NO: 90, e.g., as described herein. In any of the aforementioned embodiments, the Cas9 molecule comprises a linker between the His tag and another portion of the molecule, e.g., a GGS linker. Amino acid sequences of exemplary Cas9 molecules described above are provided below. In some embodiments, a Cas9 molecule comprises an amino sequence having at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% homology with; differs at no more than 1%, 2%, 5%, 10%, 15%, 20%, 30%, or 40% of the amino acid residues when compared with; differs by at least 1, 2, 5, 10 or 20 amino acids but by no more than 100, 80, 70, 60, 50, 40 or 30 amino acids from; or is identical to to a Cas9 sequence provided herein, e.g., SEQ ID NO: 90, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, or SEQ ID NO: 123. “iProt” identifiers match those in FIG. 1 .

›GUUGGAACCAUUCAAAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUA · 8 of 12

iProt105026 (also referred to as iProt106154, iProt106331, iProt106545, and PID426303, depending on the preparation of the protein)

(SEQ ID NO: 111): MAPKKKRKVD KKYSIGLDIG TNSVGWAVIT DEYKVPSKKF KVLGNTDRHS IKKNLIGALL FDSGETAEAT RLKRTARRRY TRRKNRICYL QEIFSNEMAK VDDSFFHRLE ESFLVEEDKK HERHPIFGNI VDEVAYHEKY PTIYHLRKKL VDSTDKADLR LIYLALAHMI KFRGHFLIEG DLNPDNSDVD KLFIQLVQTY NQLFEENPIN ASGVDAKAIL SARLSKSRRL ENLIAQLPGE KKNGLFGNLI ALSLGLTPNF KSNFDLAEDA KLQLSKDTYD DDLDNLLAQI GDQYADLFLA AKNLSDAILL SDILRVNTEI TKAPLSASMI KRYDEHHQDL TLLKALVRQQ LPEKYKEIFF DQSKNGYAGY IDGGASQEEF YKFIKPILEK MDGTEELLVK LNREDLLRKQ RTFDNGSIPH QIHLGELHAI LRRQEDFYPF LKDNREKIEK ILTFRIPYYV GPLARGNSRF AWMTRKSEET ITPWNFEEVV DKGASAQSFI ERMTNFDKNL PNEKVLPKHS LLYEYFTVYN ELTKVKYVTE GMRKPAFLSG EQKKAIVDLL FKINRKVIVK QLKEDYFKKI ECFDSVEISG VEDRFNASLG TYHDLLKIIK DKDFLDNEEN EDILEDIVLT LTLFEDREMI EERLKTYAHL FDDKVMKQLK RRRYTGWGRL SRKLINGIRD KQSGKTILDF LKSDGFANRN FMQLIHDDSL TFKEDIQKAQ VSGQGDSLHE HIANLAGSPA IKKGILQTVK VVDELVKVMG RHKPENIVIE MARENQTTQK GQKNSRERMK RIEEGIKELG SQILKEHPVE NTQLQNEKLY LYYLQNGRDM YVDQELDINR LSDYDVDHIV PQSFLKDDSI DNKVLTRSDK NRGKSDNVPS EEVVKKMKNY WRQLLNAKLI TQRKFDNLIK AERGGLSELD KAGFIKRQLV ETRQITKHVA QILDSRMNTK YDENDKLIRE VKVITLKSKL VSDFRKDFQF YKVREINNYH HAHDAYLNAV VGTALIKKYP KLESEFVYGD YKVYDVRKMI AKSEQEIGKA TAKYFFYSNI MNFFKTEITL ANGEIRKRPL IETNGETGEI VWDKGRDFAT VRKVLSMPQV NIVKKTEVQT GGFSKESILP KRNSDKLIAR KKDWDPKKYG GFDSPTVAYS VLVVAKVEKG KSKKLKSVKE LLGITIMERS SFEKNPIDFL EAKGYKEVKK DLIIKLPKYS LFELENGRKR MLASAGELQK GNELALPSKY VNFLYLASHY EKLKGSPEDN EQKQLFVEQH KHYLDEIIEQ ISEFSKRVIL ADANLDKVLS AYNKHRDKPI REQAENIIHL FTLTNLGAPA AFKYFDTTID RKRYTSTKEV LDATLIHQSI TGLYETRIDL SQLGGDSRAD PKKKRKVHHH HHH; iProt106518 (SEQ ID NO: 112): MAPKKKRKVD KKYSIGLDIG TNSVGWAVIT DEYKVPSKKF KVLGNTDRHS IKKNLIGALL FDSGETAEAT RLKRTARRRY TRRKNRILYL QEIFSNEMAK VDDSFFHRLE ESFLVEEDKK HERHPIFGNI VDEVAYHEKY PTIYHLRKKL VDSTDKADLR LIYLALAHMI KFRGHFLIEG DLNPDNSDVD KLFIQLVQTY NQLFEENPIN ASGVDAKAIL SARLSKSRRL ENLIAQLPGE KKNGLFGNLI ALSLGLTPNF KSNFDLAEDA KLQLSKDTYD DDLDNLLAQI GDQYADLFLA AKNLSDAILL SDILRVNTEI TKAPLSASMI KRYDEHHQDL TLLKALVRQQ LPEKYKEIFF DQSKNGYAGY IDGGASQEEF YKFIKPILEK MDGTEELLVK LNREDLLRKQ RTFDNGSIPH QIHLGELHAI LRRQEDFYPF LKDNREKIEK ILTFRIPYYV GPLARGNSRF AWMTRKSEET ITPWNFEEVV DKGASAQSFI ERMTNFDKNL PNEKVLPKHS LLYEYFTVYN ELTKVKYVTE GMRKPAFLSG EQKKAIVDLL FKINRKVIVK QLKEDYFKKI EEFDSVEISG VEDRFNASLG TYHDLLKIIK DKDFLDNEEN EDILEDIVLT LTLFEDREMI EERLKTYAHL FDDKVMKQLK RRRYTGWGRL SRKLINGIRD KQSGKTILDF LKSDGFANRN FMQLIHDDSL TFKEDIQKAQ VSGQGDSLHE HIANLAGSPA IKKGILQTVK VVDELVKVMG RHKPENIVIE MARENQTTQK GQKNSRERMK RIEEGIKELG SQILKEHPVE NTQLQNEKLY LYYLQNGRDM YVDQELDINR LSDYDVDHIV PQSFLKDDSI DNKVLTRSDK NRGKSDNVPS EEVVKKMKNY WRQLLNAKLI TQRKFDNLIK AERGGLSELD KAGFIKRQLV ETRQITKHVA QILDSRMNTK YDENDKLIRE VKVITLKSKL VSDFRKDFQF YKVREINNYH HAHDAYLNAV VGTALIKKYP KLESEFVYGD YKVYDVRKMI AKSEQEIGKA TAKYFFYSNI MNFFKTEITL ANGEIRKRPL IETNGETGEI VWDKGRDFAT VRKVLSMPQV NIVKKTEVQT GGFSKESILP KRNSDKLIAR KKDWDPKKYG GFDSPTVAYS VLVVAKVEKG KSKKLKSVKE LLGITIMERS SFEKNPIDFL EAKGYKEVKK DLIIKLPKYS LFELENGRKR MLASAGELQK GNELALPSKY VNFLYLASHY EKLKGSPEDN EQKQLFVEQH KHYLDEIIEQ ISEFSKRVIL ADANLDKVLS AYNKHRDKPI REQAENIIHL FTLTNLGAPA AFKYFDTTID RKRYTSTKEV LDATLIHQSI TGLYETRIDL SQLGGDSRAD PKKKRKVHHH HHH iProt106519 (SEQ ID NO: 113): MGSSHHHHHH HHENLYFQGS MDKKYSIGLD IGTNSVGWAV ITDEYKVPSK KFKVLGNTDR HSIKKNLIGA LLFDSGETAE ATRLKRTARR RYTRRKNRIC YLQEIFSNEM AKVDDSFFHR LEESFLVEED KKHERHPIFG NIVDEVAYHE KYPTIYHLRK KLVDSTDKAD LRLIYLALAH MIKFRGHFLI EGDLNPDNSD VDKLFIQLVQ TYNQLFEENP INASGVDAKA ILSARLSKSR RLENLIAQLP GEKKNGLFGN LIALSLGLTP NFKSNFDLAE DAKLQLSKDT YDDDLDNLLA QIGDQYADLF LAAKNLSDAI LLSDILRVNT EITKAPLSAS MIKRYDEHHQ DLTLLKALVR QQLPEKYKEI FFDQSKNGYA GYIDGGASQE EFYKFIKPIL EKMDGTEELL VKLNREDLLR KQRTFDNGSI PHQIHLGELH AILRRQEDFY PFLKDNREKI EKILTFRIPY YVGPLARGNS RFAWMTRKSE ETITPWNFEE VVDKGASAQS FIERMTNFDK NLPNEKVLPK HSLLYEYFTV YNELTKVKYV TEGMRKPAFL SGEQKKAIVD LLFKINRKVT VKQLKEDYFK KIECFDSVEI SGVEDRFNAS LGTYHDLLKI IKDKDFLDNE ENEDILEDIV LTLTLFEDRE MIEERLKTYA HLFDDKVMKQ LKRRRYTGWG RLSRKLINGI RDKQSGKTIL DFLKSDGFAN RNFMQLIHDD SLTFKEDIQK AQVSGQGDSL HEHIANLAGS PAIKKGILQT VKVVDELVKV MGRHKPENIV IEMARENQTT QKGQKNSRER MKRIEEGIKE LGSQILKEHP VENTQLQNEK LYLYYLQNGR DMYVDQELDI NRLSDYDVDH IVPQSFLKDD SIDNKVLTRS DKNRGKSDNV PSEEVVKKMK NYWRQLLNAK LITQRKFDNL TKAERGGLSE LDKAGFIKRQ LVETRQITKH VAQILDSRMN TKYDENDKLI REVKVITLKS KLVSDFRKDF QFYKVREINN YHHAHDAYLN AVVGTALIKK YPKLESEFVY GDYKVYDVRK MIAKSEQEIG KATAKYFFYS NIMNFFKTEI TLANGEIRKR PLIETNGETG EIVWDKGRDF ATVRKVLSMP QVNIVKKTEV QTGGFSKESI LPKRNSDKLI ARKKDWDPKK YGGFDSPTVA YSVLVVAKVE KGKSKKLKSV KELLGITIME RSSFEKNPID FLEAKGYKEV KKDLIIKLPK YSLFELENGR KRMLASAGEL QKGNELALPS KYVNFLYLAS HYEKLKGSPE DNEQKQLFVE QHKHYLDEII EQISEFSKRV ILADANLDKV LSAYNKHRDK PIREQAENII HLFTLTNLGA PAAFKYFDTT IDRKRYTSTK EVLDATLIHQ SITGLYETRI DLSQLGGDGG GSPKKKRKV iProt106520 (SEQ ID NO: 114): MAHHHHHHGG SPKKKRKVDK KYSIGLDIGT NSVGWAVITD EYKVPSKKFK VLGNTDRHSI KKNLIGALLF DSGETAEATR LKRTARRRYT RRKNRICYLQ EIFSNEMAKV DDSFFHRLEE SFLVEEDKKH ERHPIFGNIV DEVAYHEKYP TIYHLRKKLV DSTDKADLRL IYLALAHMIK FRGHFLIEGD LNPDNSDVDK LFIQLVQTYN QLFEENPINA SGVDAKAILS ARLSKSRRLE NLIAQLPGEK KNGLFGNLIA LSLGLTPNFK SNFDLAEDAK LQLSKDTYDD DLDNLLAQIG DQYADLFLAA KNLSDAILLS DILRVNTEIT KAPLSASMIK RYDEHHQDLT LLKALVRQQL PEKYKEIFFD QSKNGYAGYI DGGASQEEFY KFIKPILEKM DGTEELLVKL NREDLLRKQR TFDNGSIPHQ IHLGELHAIL RRQEDFYPFL KDNREKIEKI LTFRIPYYVG PLARGNSRFA WMTRKSEETI TPWNFEEVVD KGASAQSFIE RMTNFDKNLP NEKVLPKHSL LYEYFTVYNE LTKVKYVTEG MRKPAFLSGE QKKAIVDLLF KINRKVIVKQ LKEDYFKKIE CFDSVEISGV EDRFNASLGT YHDLLKIIKD KDFLDNEENE DILEDIVLTL TLFEDREMIE ERLKTYAHLF DDKVMKQLKR RRYTGWGRLS RKLINGIRDK QSGKTILDFL KSDGFANRNF MQLIHDDSLT FKEDIQKAQV SGQGDSLHEH IANLAGSPAI KKGILQTVKV VDELVKVMGR HKPENIVIEM ARENQTTQKG QKNSRERMKR IEEGIKELGS QILKEHPVEN TQLQNEKLYL YYLQNGRDMY VDQELDINRL SDYDVDHIVP QSFLKDDSID NKVLTRSDKN RGKSDNVPSE EVVKKMKNYW RQLLNAKLIT QRKFDNLTKA ERGGLSELDK AGFIKRQLVE TRQITKHVAQ ILDSRMNTKY DENDKLIREV KVITLKSKLV SDFRKDFQFY KVREINNYHH AHDAYLNAVV GTALIKKYPK LESEFVYGDY KVYDVRKMIA KSEQEIGKAT AKYFFYSNIM NFFKTEITLA NGEIRKRPLI ETNGETGEIV WDKGRDFATV RKVLSMPQVN IVKKTEVQTG GFSKESILPK RNSDKLIARK KDWDPKKYGG FDSPTVAYSV LVVAKVEKGK SKKLKSVKEL LGITIMERSS FEKNPIDFLE AKGYKEVKKD LIIKLPKYSL FELENGRKRM LASAGELQKG NELALPSKYV NFLYLASHYE KLKGSPEDNE QKQLFVEQHK HYLDEIIEQI SEFSKRVILA DANLDKVLSA YNKHRDKPIR EQAENIIHLF TLTNLGAPAA FKYFDTTIDR KRYTSTKEVL DATLIHQSIT GLYETRIDLS QLGGDSRADP KKKRKV iProt106521 (SEQ ID NO: 115): MAPKKKRKVD KKYSIGLDIG TNSVGWAVIT DEYKVPSKKF KVLGNTDRHS IKKNLIGALL FDSGETAEAT RLKRTARRRY TRRKNRICYL QEIFSNEMAK VDDSFFHRLE ESFLVEEDKK HERHPIFGNI VDEVAYHEKY PTIYHLRKKL VDSTDKADLR LIYLALAHMI KFRGHFLIEG DLNPDNSDVD KLFIQLVQTY NQLFEENPIN ASGVDAKAIL SARLSKSRRL ENLIAQLPGE KKNGLFGNLI ALSLGLTPNF KSNFDLAEDA KLQLSKDTYD DDLDNLLAQI GDQYADLFLA AKNLSDAILL SDILRVNTEI TKAPLSASMI KRYDEHHQDL TLLKALVRQQ LPEKYKEIFF DQSKNGYAGY IDGGASQEEF YKFIKPILEK MDGTEELLVK LNREDLLRKQ RTFDNGSIPH QIHLGELHAI LRRQEDFYPF LKDNREKIEK ILTFRIPYYV GPLARGNSRF AWMTRKSEET ITPWNFEEVV DKGASAQSFI ERMTNFDKNL PNEKVLPKHS LLYEYFTVYN ELTKVKYVTE GMRKPAFLSG EQKKAIVDLL FKINRKVIVK QLKEDYFKKI ECFDSVEISG VEDRFNASLG TYHDLLKIIK DKDFLDNEEN EDILEDIVLT LTLFEDREMI EERLKTYAHL FDDKVMKQLK RRRYTGWGRL SRKLINGIRD KQSGKTILDF LKSDGFANRN FMQLIHDDSL TFKEDIQKAQ VSGQGDSLHE HIANLAGSPA IKKGILQTVK VVDELVKVMG RHKPENIVIE MARENQTTQK GQKNSRERMK RIEEGIKELG SQILKEHPVE NTQLQNEKLY LYYLQNGRDM YVDQELDINR LSDYDVDHIV PQSFLKDDSI DNKVLTRSDK NRGKSDNVPS EEVVKKMKNY WRQLLNAKLI TQRKFDNLIK AERGGLSELD KAGFIKRQLV ETRQITKHVA QILDSRMNTK YDENDKLIRE VKVITLKSKL VSDFRKDFQF YKVREINNYH HAHDAYLNAV VGTALIKKYP KLESEFVYGD YKVYDVRKMI AKSEQEIGKA TAKYFFYSNI MNFFKTEITL ANGEIRKRPL IETNGETGEI VWDKGRDFAT VRKVLSMPQV NIVKKTEVQT GGFSKESILP KRNSDKLIAR KKDWDPKKYG GFDSPTVAYS VLVVAKVEKG KSKKLKSVKE LLGITIMERS SFEKNPIDFL EAKGYKEVKK DLIIKLPKYS LFELENGRKR MLASAGELQK GNELALPSKY VNFLYLASHY EKLKGSPEDN EQKQLFVEQH KHYLDEIIEQ ISEFSKRVIL ADANLDKVLS AYNKHRDKPI REQAENIIHL FTLTNLGAPA AFKYFDTTID RKRYTSTKEV LDATLIHQSI TGLYETRIDL SQLGGDSRAD HHHHHH iProt106522 (SEQ ID NO: 116): MAHHHHHHGG SDKKYSIGLD IGTNSVGWAV ITDEYKVPSK KFKVLGNTDR HSIKKNLIGA LLFDSGETAE ATRLKRTARR RYTRRKNRIC YLQEIFSNEM AKVDDSFFHR LEESFLVEED KKHERHPIFG NIVDEVAYHE KYPTIYHLRK KLVDSTDKAD LRLIYLALAH MIKFRGHFLI EGDLNPDNSD VDKLFIQLVQ TYNQLFEENP INASGVDAKA ILSARLSKSR RLENLIAQLP GEKKNGLFGN LIALSLGLTP NFKSNFDLAE DAKLQLSKDT YDDDLDNLLA QIGDQYADLF LAAKNLSDAI LLSDILRVNT EITKAPLSAS MIKRYDEHHQ DLTLLKALVR QQLPEKYKEI FFDQSKNGYA GYIDGGASQE EFYKFIKPIL EKMDGTEELL VKLNREDLLR KQRTFDNGSI PHQIHLGELH AILRRQEDFY PFLKDNREKI EKILTFRIPY YVGPLARGNS RFAWMTRKSE ETITPWNFEE VVDKGASAQS FIERMTNFDK NLPNEKVLPK HSLLYEYFTV YNELTKVKYV TEGMRKPAFL SGEQKKAIVD LLFKINRKVT VKQLKEDYFK KIECFDSVEI SGVEDRFNAS LGTYHDLLKI IKDKDFLDNE ENEDILEDIV LTLTLFEDRE MIEERLKTYA HLFDDKVMKQ LKRRRYTGWG RLSRKLINGI RDKQSGKTIL DFLKSDGFAN RNFMQLIHDD SLTFKEDIQK AQVSGQGDSL HEHIANLAGS PAIKKGILQT VKVVDELVKV MGRHKPENIV IEMARENQTT QKGQKNSRER MKRIEEGIKE LGSQILKEHP VENTQLQNEK LYLYYLQNGR DMYVDQELDI NRLSDYDVDH IVPQSFLKDD SIDNKVLTRS DKNRGKSDNV PSEEVVKKMK NYWRQLLNAK LITQRKFDNL TKAERGGLSE LDKAGFIKRQ LVETRQITKH VAQILDSRMN TKYDENDKLI REVKVITLKS KLVSDFRKDF QFYKVREINN YHHAHDAYLN AVVGTALIKK YPKLESEFVY GDYKVYDVRK MIAKSEQEIG KATAKYFFYS NIMNFFKTEI TLANGEIRKR PLIETNGETG EIVWDKGRDF ATVRKVLSMP QVNIVKKTEV QTGGFSKESI LPKRNSDKLI ARKKDWDPKK YGGFDSPTVA YSVLVVAKVE KGKSKKLKSV KELLGITIME RSSFEKNPID FLEAKGYKEV KKDLIIKLPK YSLFELENGR KRMLASAGEL QKGNELALPS KYVNFLYLAS HYEKLKGSPE DNEQKQLFVE QHKHYLDEII EQISEFSKRV ILADANLDKV LSAYNKHRDK PIREQAENII HLFTLTNLGA PAAFKYFDTT IDRKRYTSTK EVLDATLIHQ SITGLYETRI DLSQLGGDSR ADPKKKRKV iProt106658 (SEQ ID NO: 117): MGSSHHHHHH HHENLYFQGS MDKKYSIGLD IGTNSVGWAV ITDEYKVPSK KFKVLGNTDR HSIKKNLIGA LLFDSGETAE ATRLKRTARR RYTRRKNRIC YLQEIFSNEM AKVDDSFFHR LEESFLVEED KKHERHPIFG NIVDEVAYHE KYPTIYHLRK KLVDSTDKAD LRLIYLALAH MIKFRGHFLI EGDLNPDNSD VDKLFIQLVQ TYNQLFEENP INASGVDAKA ILSARLSKSR RLENLIAQLP GEKKNGLFGN LIALSLGLTP NFKSNFDLAE DAKLQLSKDT YDDDLDNLLA QIGDQYADLF LAAKNLSDAI LLSDILRVNT EITKAPLSAS MIKRYDEHHQ DLTLLKALVR QQLPEKYKEI FFDQSKNGYA GYIDGGASQE EFYKFIKPIL EKMDGTEELL VKLNREDLLR KQRTFDNGSI PHQIHLGELH AILRRQEDFY PFLKDNREKI EKILTFRIPY YVGPLARGNS RFAWMTRKSE ETITPWNFEE VVDKGASAQS FIERMTNFDK NLPNEKVLPK HSLLYEYFTV YNELTKVKYV TEGMRKPAFL SGEQKKAIVD LLFKINRKVT VKQLKEDYFK KIECFDSVEI SGVEDRFNAS LGTYHDLLKI IKDKDFLDNE ENEDILEDIV LTLTLFEDRE MIEERLKTYA HLFDDKVMKQ LKRRRYTGWG RLSRKLINGI RDKQSGKTIL DFLKSDGFAN RNFMQLIHDD SLTFKEDIQK AQVSGQGDSL HEHIANLAGS PAIKKGILQT VKVVDELVKV MGRHKPENIV IEMARENQTT QKGQKNSRER MKRIEEGIKE LGSQILKEHP VENTQLQNEK LYLYYLQNGR DMYVDQELDI NRLSDYDVDH IVPQSFLKDD SIDNKVLTRS DKNRGKSDNV PSEEVVKKMK NYWRQLLNAK LITQRKFDNL TKAERGGLSE LDKAGFIKRQ LVETRQITKH VAQILDSRMN TKYDENDKLI REVKVITLKS KLVSDFRKDF QFYKVREINN YHHAHDAYLN AVVGTALIKK YPKLESEFVY GDYKVYDVRK MIAKSEQEIG KATAKYFFYS NIMNFFKTEI TLANGEIRKR PLIETNGETG EIVWDKGRDF ATVRKVLSMP QVNIVKKTEV QTGGFSKESI LPKRNSDKLI ARKKDWDPKK YGGFDSPTVA YSVLVVAKVE KGKSKKLKSV KELLGITIME RSSFEKNPID FLEAKGYKEV KKDLIIKLPK YSLFELENGR KRMLASAGEL QKGNELALPS KYVNFLYLAS HYEKLKGSPE DNEQKQLFVE QHKHYLDEII EQISEFSKRV ILADANLDKV LSAYNKHRDK PIREQAENII HLFTLTNLGA PAAFKYFDTT IDRKRYTSTK EVLDATLIHQ SITGLYETRI DLSQLGGDGG GSPKKKRKV iProt106745 (SEQ ID NO: 118): MAPKKKRKVD KKYSIGLDIG TNSVGWAVIT DEYKVPSKKF KVLGNTDRHS IKKNLIGALL FDSGETAEAT RLKRTARRRY TRRKNRICYL QEIFSNEMAK VDDSFFHRLE ESFLVEEDKK HERHPIFGNI VDEVAYHEKY PTIYHLRKKL VDSTDKADLR LIYLALAHMI KFRGHFLIEG DLNPDNSDVD KLFIQLVQTY NQLFEENPIN ASGVDAKAIL SARLSKSRRL ENLIAQLPGE KKNGLFGNLI ALSLGLTPNF KSNFDLAEDA KLQLSKDTYD DDLDNLLAQI GDQYADLFLA AKNLSDAILL SDILRVNTEI TKAPLSASMI KRYDEHHQDL TLLKALVRQQ LPEKYKEIFF DQSKNGYAGY IDGGASQEEF YKFIKPILEK MDGTEELLVK LNREDLLRKQ RTFDNGSIPH QIHLGELHAI LRRQEDFYPF LKDNREKIEK ILTFRIPYYV GPLARGNSRF AWMTRKSEET ITPWNFEEVV DKGASAQSFI ERMTNFDKNL PNEKVLPKHS LLYEYFTVYN ELTKVKYVTE GMRKPAFLSG EQKKAIVDLL FKINRKVIVK QLKEDYFKKI ECFDSVEISG VEDRFNASLG TYHDLLKIIK DKDFLDNEEN EDILEDIVLT LTLFEDREMI EERLKTYAHL FDDKVMKQLK RRRYTGWGRL SRKLINGIRD KQSGKTILDF LKSDGFANRN FMQLIHDDSL TFKEDIQKAQ VSGQGDSLHE HIANLAGSPA IKKGILQTVK VVDELVKVMG RHKPENIVIE MARENQTTQK GQKNSRERMK RIEEGIKELG SQILKEHPVE NTQLQNEKLY LYYLQNGRDM YVDQELDINR LSDYDVDHIV PQSFLKDDSI DNAVLTRSDK NRGKSDNVPS EEVVKKMKNY WRQLLNAKLI TQRKFDNLIK AERGGLSELD KAGFIKRQLV ETRQITKHVA QILDSRMNTK YDENDKLIRE VKVITLKSKL VSDFRKDFQF YKVREINNYH HAHDAYLNAV VGTALIKKYP KLESEFVYGD YKVYDVRKMI AKSEQEIGKA TAKYFFYSNI MNFFKTEITL ANGEIRKRPL IETNGETGEI VWDKGRDFAT VRKVLSMPQV NIVKKTEVQT GGFSKESILP KRNSDKLIAR KKDWDPKKYG GFDSPTVAYS VLVVAKVEKG KSKKLKSVKE LLGITIMERS SFEKNPIDFL EAKGYKEVKK DLIIKLPKYS LFELENGRKR MLASAGELQK GNELALPSKY VNFLYLASHY EKLKGSPEDN EQKQLFVEQH KHYLDEIIEQ ISEFSKRVIL ADANLDKVLS AYNKHRDKPI REQAENIIHL FTLTNLGAPA AFKYFDTTID RKRYTSTKEV LDATLIHQSI TGLYETRIDL SQLGGDSRAD PKKKRKVHHH HHH iProt106746 (SEQ ID NO: 119): MAPKKKRKVD KKYSIGLDIG TNSVGWAVIT DEYKVPSKKF KVLGNTDRHS IKKNLIGALL FDSGETAEAT RLKRTARRRY TRRKNRICYL QEIFSNEMAK VDDSFFHRLE ESFLVEEDKK HERHPIFGNI VDEVAYHEKY PTIYHLRKKL VDSTDKADLR LIYLALAHMI KFRGHFLIEG DLNPDNSDVD KLFIQLVQTY NQLFEENPIN ASGVDAKAIL SARLSKSRRL ENLIAQLPGE KKNGLFGNLI ALSLGLTPNF KSNFDLAEDA KLQLSKDTYD DDLDNLLAQI GDQYADLFLA AKNLSDAILL SDILRVNTEI TKAPLSASMI KRYDEHHQDL TLLKALVRQQ LPEKYKEIFF DQSKNGYAGY IDGGASQEEF YKFIKPILEK MDGTEELLVK LNREDLLRKQ RTFDNGSIPH QIHLGELHAI LRRQEDFYPF LKDNREKIEK ILTFRIPYYV GPLARGNSRF AWMTRKSEET ITPWNFEEVV DKGASAQSFI ERMTNFDKNL PNEKVLPKHS LLYEYFTVYN ELTKVKYVTE GMRKPAFLSG EQKKAIVDLL FKINRKVIVK QLKEDYFKKI ECFDSVEISG VEDRFNASLG TYHDLLKIIK DKDFLDNEEN EDILEDIVLT LTLFEDREMI EERLKTYAHL FDDKVMKQLK RRRYTGWGRL SRKLINGIRD KQSGKTILDF LKSDGFANRN FMQLIHDDSL TFKEDIQKAQ VSGQGDSLHE HIANLAGSPA IKKGILQTVK VVDELVKVMG RHKPENIVIE MARENQTTQK GQKNSRERMK RIEEGIKELG SQILKEHPVE NTQLQNEALY LYYLQNGRDM YVDQELDINR LSDYDVDHIV PQSFLKDDSI DNKVLTRSDK NRGKSDNVPS EEVVKKMKNY WRQLLNAKLI TQRKFDNLIK AERGGLSELD KAGFIKRQLV ETRQITKHVA QILDSRMNTK YDENDKLIRE VKVITLKSKL VSDFRKDFQF YKVREINNYH HAHDAYLNAV VGTALIKKYP ALESEFVYGD YKVYDVRKMI AKSEQEIGKA TAKYFFYSNI MNFFKTEITL ANGEIRKAPL IETNGETGEI VWDKGRDFAT VRKVLSMPQV NIVKKTEVQT GGFSKESILP KRNSDKLIAR KKDWDPKKYG GFDSPTVAYS VLVVAKVEKG KSKKLKSVKE LLGITIMERS SFEKNPIDFL EAKGYKEVKK DLIIKLPKYS LFELENGRKR MLASAGELQK GNELALPSKY VNFLYLASHY EKLKGSPEDN EQKQLFVEQH KHYLDEIIEQ ISEFSKRVIL ADANLDKVLS AYNKHRDKPI REQAENIIHL FTLTNLGAPA AFKYFDTTID RKRYTSTKEV LDATLIHQSI TGLYETRIDL SQLGGDSRAD PKKKRKVHHH HHH iProt106747 (SEQ ID NO: 120): MAPKKKRKVD KKYSIGLDIG TNSVGWAVIT DEYKVPSKKF KVLGNTDRHS IKKNLIGALL FDSGETAEAT RLKRTARRRY TRRKNRICYL QEIFSNEMAK VDDSFFHRLE ESFLVEEDKK HERHPIFGNI VDEVAYHEKY PTIYHLRKKL VDSTDKADLR LIYLALAHMI KFRGHFLIEG DLNPDNSDVD KLFIQLVQTY NQLFEENPIN ASGVDAKAIL SARLSKSRRL ENLIAQLPGE KKNGLFGNLI ALSLGLTPNF KSNFDLAEDA KLQLSKDTYD DDLDNLLAQI GDQYADLFLA AKNLSDAILL SDILRVNTEI TKAPLSASMI KRYDEHHQDL TLLKALVRQQ LPEKYKEIFF DQSKNGYAGY IDGGASQEEF YKFIKPILEK MDGTEELLVK LNREDLLRKQ RTFDNGSIPH QIHLGELHAI LRRQEDFYPF LKDNREKIEK ILTFRIPYYV GPLARGNSRF AWMTRKSEET ITPWNFEEVV DKGASAQSFI ERMTNFDKNL PNEKVLPKHS LLYEYFTVYN ELTKVKYVTE GMRKPAFLSG EQKKAIVDLL FKINRKVIVK QLKEDYFKKI ECFDSVEISG VEDRFNASLG TYHDLLKIIK DKDFLDNEEN EDILEDIVLT LTLFEDREMI EERLKTYAHL FDDKVMKQLK RRRYTGWGRL SRKLINGIRD KQSGKTILDF LKSDGFANRN FMQLIHDDSL TFKEDIQKAQ VSGQGDSLHE HIANLAGSPA IKKGILQTVK VVDELVKVMG RHKPENIVIE MARENQTTQK GQKNSRERMK RIEEGIKELG SQILKEHPVE NTQLQNEKLY LYYLQNGRDM YVDQELDINR LSDYDVDHIV PQSFLADDSI DNKVLTRSDK NRGKSDNVPS EEVVKKMKNY WRQLLNAKLI TQRKFDNLIK AERGGLSELD KAGFIKRQLV ETRQITKHVA QILDSRMNTK YDENDKLIRE VKVITLKSKL VSDFRKDFQF YKVREINNYH HAHDAYLNAV VGTALIKKYP ALESEFVYGD YKVYDVRKMI AKSEQEIGKA TAKYFFYSNI MNFFKTEITL ANGEIRKAPL IETNGETGEI VWDKGRDFAT VRKVLSMPQV NIVKKTEVQT GGFSKESILP KRNSDKLIAR KKDWDPKKYG GFDSPTVAYS VLVVAKVEKG KSKKLKSVKE LLGITIMERS SFEKNPIDFL EAKGYKEVKK DLIIKLPKYS LFELENGRKR MLASAGELQK GNELALPSKY VNFLYLASHY EKLKGSPEDN EQKQLFVEQH KHYLDEIIEQ ISEFSKRVIL ADANLDKVLS AYNKHRDKPI REQAENIIHL FTLTNLGAPA AFKYFDTTID RKRYTSTKEV LDATLIHQSI TGLYETRIDL SQLGGDSRAD PKKKRKVHHH HHH iProt106884 (SEQ ID NO: 121): MAPKKKRKVD KKYSIGLDIG TNSVGWAVIT DEYKVPSKKF KVLGNTDRHS IKKNLIGALL FDSGETAEAT RLKRTARRRY TRRKNRICYL QEIFSNEMAK VDDSFFHRLE ESFLVEEDKK HERHPIFGNI VDEVAYHEKY PTIYHLRKKL VDSTDKADLR LIYLALAHMI KFRGHFLIEG DLNPDNSDVD KLFIQLVQTY NQLFEENPIN ASGVDAKAIL SARLSKSRRL ENLIAQLPGE KKNGLFGNLI ALSLGLTPNF KSNFDLAEDA KLQLSKDTYD DDLDNLLAQI GDQYADLFLA AKNLSDAILL SDILRVNTEI TKAPLSASMI KRYDEHHQDL TLLKALVRQQ LPEKYKEIFF DQSKNGYAGY IDGGASQEEF YKFIKPILEK MDGTEELLVK LNREDLLRKQ RTFDNGSIPH QIHLGELHAI LRRQEDFYPF LKDNREKIEK ILTFRIPYYV GPLARGNSRF AWMTRKSEET ITPWNFEEVV DKGASAQSFI ERMTAFDKNL PNEKVLPKHS LLYEYFTVYN ELTKVKYVTE GMRKPAFLSG EQKKAIVDLL FKTNRKVTVK QLKEDYFKKI ECFDSVEISG VEDRFNASLG TYHDLLKIIK DKDFLDNEEN EDILEDIVLT LTLFEDREMI EERLKTYAHL FDDKVMKQLK RRRYTGWGAL SRKLINGIRD KQSGKTILDF LKSDGFANRN FMALIHDDSL TFKEDIQKAQ VSGQGDSLHE HIANLAGSPA IKKGILQTVK VVDELVKVMG RHKPENIVIE MARENQTTQK GQKNSRERMK RIEEGIKELG SQILKEHPVE NTQLQNEKLY LYYLQNGRDM YVDQELDINR LSDYDVDHIV PQSFLKDDSI DNKVLTRSDK NRGKSDNVPS EEVVKKMKNY WRQLLNAKLI TQRKFDNLTK AERGGLSELD KAGFIKRQLV ETRAITKHVA QILDSRMNTK YDENDKLIRE VKVITLKSKL VSDFRKDFQF YKVREINNYH HAHDAYLNAV VGTALIKKYP KLESEFVYGD YKVYDVRKMI AKSEQEIGKA TAKYFFYSNI MNFFKTEITL ANGEIRKRPL IETNGETGEI VWDKGRDFAT VRKVLSMPQV NIVKKTEVQT GGFSKESILP KRNSDKLIAR KKDWDPKKYG GFDSPTVAYS VLVVAKVEKG KSKKLKSVKE LLGITIMERS SFEKNPIDFL EAKGYKEVKK DLIIKLPKYS LFELENGRKR MLASAGELQK GNELALPSKY VNFLYLASHY EKLKGSPEDN EQKQLFVEQH KHYLDEIIEQ ISEFSKRVIL ADANLDKVLS AYNKHRDKPI REQAENIIHL FTLTNLGAPA AFKYFDTTID RKRYTSTKEV LDATLIHQSI TGLYETRIDL SQLGGDSRAD PKKKRKVHHH HHH iPROT 109496 (SEQ ID NO: 123): MAPKKKRKVDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDS GETAEATRLKRTARRRYTRRKNRILYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPI FGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDV DKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIAL SLGLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILR VNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQE EFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFL KDNREKIEKILTFRIPYYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMT NFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKV TVKQLKEDYFKKIEEFDSVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLT LTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKS DGFANRNFMQLIHDDSLTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELV KVMGRHKPENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKL YLYYLQNGRDMYVDQELDINRLSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEE VVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDS RMNTKYDENDKLIREVKVITLKSKLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKK YPKLESEFVYGDYKVYDVRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLI ETNGETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDW DPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKE VKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDN EQKQLFVEQHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTL TNLGAPAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGDSRADHHHHHH

›GUUGGAACCAUUCAAAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUA · 9 of 12

Nucleic Acids Encoding Cas9 Molecules

Nucleic acids encoding the Cas9 molecules discussed above, e.g., an active Cas9 molecule or an inactive Cas9 molecule are provided herein.

Exemplary nucleic acids encoding Cas9 molecules are described in Cong et al, SCIENCE 2013, 399(6121):819-823; Wang et al, CELL 2013, 153(4):910-918; Mali et al., SCIENCE 2013, 399(6121):823-826; Jinek et al, SCIENCE 2012, 337(6096):816-821.

In an embodiment, a nucleic acid encoding a Cas9 molecule can be a synthetic nucleic acid sequence. For example, the synthetic nucleic acid molecule can be chemically modified, e.g., as described in Section XIII. In an embodiment, the Cas9 mRNA has one or more of, e.g., all of the following properties: it is capped, polyadenylated, substituted with 5-methylcytidine and/or pseudouridine.

In addition or alternatively, the synthetic nucleic acid sequence can be codon optimized, e.g., at least one non-common codon or less-common codon has been replaced by a common codon. For example, the synthetic nucleic acid can direct the synthesis of an optimized messenger mRNA, e.g., optimized for expression in a mammalian expression system, e.g., described herein.

Provided below is an exemplary codon optimized nucleic acid sequence encoding a Cas9 molecule of S. pyogenes .

If a Cas9 sequence, e.g., the sequence listed above, is fused with a peptide or polypeptide at the C-terminus (e.g., an inactive Cas9 fused with a transcription repressor at the C-terminus), it is understood that the stop codon will be removed.

V. Chimeric Antigen Receptors

Disclosed herein are chimeric antigen receptor (CAR) immune effector cells, e.g., T cells, or chimeric TCR-transduced immune effector cells, e.g., T cells. In particular, disclosed herein are improved CAR immune effector cells modified in a tet gene intron or intron-exon junction, for example at a TET2 intron or intron-exon junction, for example, at the intron between exons 9 and 10 of TET2. In some embodiments, disclosed herein are CAR immune effector cells that have been modified to exhibit partial (but not full) inhibition of the function and/or expression of TET2 to enhance immune effector cell function. In some embodiments, disclosed herein are CAR immune effector cells that have been modified to exhibit full inhibition of the function and/or expression of TET2 to enhance immune effector cell function. In some embodiments, the CAR immune effector cells are modified in a tet gene intron or intron-exon junction, for example at a TET2 intron or intron-exon junction, to specifically disrupt TET2 function and/or insert a heterologous protein specifically at that position. In some embodiments, the disclosure provides for gRNA molecules and CRISPR systems for use in connection with these adoptive immunotherapy methods and reagents to produce CAR immune effector cells, e.g., T cells, or chimeric TCR-transduced immune effector cells, e.g., T cells. The gRNA molecules and CRISPR systems of the disclosure can be used to create adoptive immunotherapy cells and compositions with improved properties, such as efficacy and safety. This section describes, in some embodiments, CAR technology in conjunction with the gRNA molecules and CRISPR systems of the disclosure, and describes improved CAR reagents, e.g., cells and compositions, and methods. Other methods for inserting chimeric antigen receptors into immune effector cells can also be employed, including those described herein or otherwise known to the skilled artisan.

In general, aspects of the disclosure pertain to or include an isolated nucleic acid molecule encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen binding domain (e.g., antibody or antibody fragment, TCR or TCR fragment) that binds to a tumor antigen as described herein, a transmembrane domain (e.g., a transmembrane domain described herein), and an intracellular signaling domain (e.g., an intracellular signaling domain described herein). In various embodiments, the intracellular signaling domain comprises a costimulatory domain (e.g., a costimulatory domain described herein) and/or a primary signaling domain (e.g., a primary signaling domain described herein).

In other aspects, the disclosure includes: host cells containing the above nucleic acids and isolated proteins encoded by such nucleic acid molecules. CAR nucleic acid constructs, encoded proteins, vectors containing the CAR nucleic acid constructs, host cells, pharmaceutical compositions, and methods of administration and treatment are also disclosed herein. Further details on their preparation and use are provided in International Patent Application Publication No. WO2015142675, which is incorporated by reference in its entirety.

In one aspect, the disclosure pertains to a chimeric antigen receptor (CAR) and/or an isolated nucleic acid molecule encoding the CAR, wherein the CAR comprises an antigen binding domain (e.g., antibody or antibody fragment, TCR or TCR fragment) that binds to a tumor-supporting antigen (e.g., a tumor-supporting antigen as described herein), a transmembrane domain (e.g., a transmembrane domain described herein), and an intracellular signaling domain (e.g., an intracellular signaling domain described herein. In some embodiments, the intracellular signaling domain comprises a costimulatory domain (e.g., an intracellular signaling domain comprising a costimulatory domain (e.g., a costimulatory domain described herein) and/or a primary signaling domain (e.g., a primary signaling domain described herein). In some embodiments, the tumor-supporting antigen is an antigen present on a stromal cell or a myeloid-derived suppressor cell (MDSC). In other aspects, the disclosure features polypeptides encoded by such nucleic acids and host cells containing such nucleic acids and/or polypeptides.

Alternatively, aspects of the disclosure pertain to isolated nucleic acid encoding a chimeric T cell receptor (TCR) comprising a TCR alpha and/or TCR beta variable domain with specificity for a cancer antigen described herein. See for example, Dembic et al., Nature, 320, 232-238 (1986), Schumacher, Nat. Rev. Immunol., 2, 512-519 (2002), Kershaw et al., Nat. Rev. Immnol., 5, 928-940 (2005), Xue et al., Clin. KvEp. Immunol, 139, 167-172 (2005), Rossig et al., Mol. Ther., 10, 5-18 (2004), and Murphy et al., Immunity, 22, 403-414 (2005); (Morgan et al., J. Immunol., 171, 3287-3295 (2003), Hughes et al., Hum. Gene Ther., 16, 1-16 (2005), Zhao et al., J. Immunol., 174, 4415-4423 (2005). Roszkowski et al, Cancer Res., 65, 1570-1576 (2005), and Engels et al., Hun. Gene Ther., 16, 799-810 (2005); US2009/03046557, the contents of which are hereby incorporated by reference in their entirety. Such chimeric TCRs may recognize, for example, cancer antigens such as MART-1, gp-100, p53, and NY-ESO-1, MAGE A3/A6, MAGEA3, SSX2, HPV-16 E6 or HPV-16 E7. In other aspects, the disclosure features polypeptides encoded by such nucleic acids and host cells containing such nucleic acids and/or polypeptides.

›GUUGGAACCAUUCAAAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUA · 10 of 12

Targets

The present disclosure provides cells, e.g., immune effector cells (e.g., T cells, NK cells), that comprise or at any time comprised a gRNA molecule or CRISPR system as described herein, that are further engineered to contain one or more CARs that direct the immune effector cells to undesired cells (e.g., cancer cells). This is achieved through an antigen binding domain on the CAR that is specific for a cancer associated antigen. There are two classes of cancer associated antigens (tumor antigens) that can be targeted by the CARs of the instant disclosure: (1) a cancer associated antigens that is expressed on the surface of a cancer cell; and (2) a cancer-associated antigen that itself is intracellular, however, a fragment of such antigen (peptide) is presented on the surface of the cancer cells by MHC (major histocompatibility complex).

In some embodiments, the tumor antigen is chosen from one or more of: CD19; CD123; CD22; CD30; CD171; CS-1 (also referred to as CD2 subset 1, CRACC, SLAMF7, CD319, and 19A24); C-type lectin-like molecule-1 (CLL-1 or CLECL1); CD33; epidermal growth factor receptor variant III (EGFRvIII); ganglioside G2 (GD2); ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDGlcp(1-1)Cer); TNF receptor family member B cell maturation (BCMA); Tn antigen ((Tn Ag) or (GalNAca-Ser/Thr)); prostate-specific membrane antigen (PSMA); Receptor tyrosine kinase-like orphan receptor 1 (ROR1); Fms-Like Tyrosine Kinase 3 (FLT3); Tumor-associated glycoprotein 72 (TAG72); CD38; CD44v6; Carcinoembryonic antigen (CEA); Epithelial cell adhesion molecule (EPCAM); B7H3 (CD276); KIT (CD117); Interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2); Mesothelin; Interleukin 11 receptor alpha (IL-11Ra); prostate stem cell antigen (PSCA); Protease Serine 21 (Testisin or PRSS21); vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; Platelet-derived growth factor receptor beta (PDGFR-beta); Stage-specific embryonic antigen-4 (SSEA-4); CD20; Folate receptor alpha; Receptor tyrosine-protein kinase ERBB2 (Her2/neu); Mucin 1, cell surface associated (MUC1); epidermal growth factor receptor (EGFR); neural cell adhesion molecule (NCAM); Prostase; prostatic acid phosphatase (PAP); elongation factor 2 mutated (ELF2M); Ephrin B2; fibroblast activation protein alpha (FAP); insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CAIX); Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2); glycoprotein 100 (gp100); oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl) (bcr-abl); tyrosinase; ephrin type-A receptor 2 (EphA2); Fucosyl GM1; sialyl Lewis adhesion molecule (sLe); ganglioside GM3 (aNeu5Ac(2-3)bDGalp(1-4)bDGlcp(1-1)Cer); transglutaminase 5 (TGS5); high molecular weight-melanoma-associated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); Folate receptor beta; tumor endothelial marker 1 (TEM1/CD248); tumor endothelial marker 7-related (TEM7R); claudin 6 (CLDN6); thyroid stimulating hormone receptor (TSHR); G protein-coupled receptor class C group 5, member D (GPRC5D); chromosome X open reading frame 61 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); Polysialic acid; placenta-specific 1 (PLAC1); hexasaccharide portion of globoH glycoceramide (GloboH); mammary gland differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); Hepatitis A virus cellular receptor 1 (HAVCR1); adrenoceptor beta 3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); lymphocyte antigen 6 complex, locus K 9 (LY6K); Olfactory receptor 51E2 (OR51E2); TCR Gamma Alternate Reading Frame Protein (TARP); Wilms tumor protein (WT1); Cancer/testis antigen 1 (NY-ESO-1); Cancer/testis antigen 2 (LAGE-1a); Melanoma-associated antigen 1 (MAGE-A1); ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); X Antigen Family, Member 1A (XAGE1); angiopoietin-binding cell surface receptor 2 (Tie 2); melanoma cancer testis antigen-1 (MAD-CT-1); melanoma cancer testis antigen-2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p53); p53 mutant; prostein; surviving; telomerase; prostate carcinoma tumor antigen-1 (PCTA-1 or Galectin 8), melanoma antigen recognized by T cells 1 (MelanA or MART1); Rat sarcoma (Ras) mutant; human Telomerase reverse transcriptase (hTERT); sarcoma translocation breakpoints; melanoma inhibitor of apoptosis (ML-IAP); ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene); N-Acetyl glucosaminyl-transferase V (NA17); paired box protein Pax-3 (PAX3); Androgen receptor; Cyclin B1; v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN); Ras Homolog Family Member C (RhoC); Tyrosinase-related protein 2 (TRP-2); Cytochrome P450 1B1 (CYP1B1); CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS or Brother of the Regulator of Imprinted Sites), Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3); Paired box protein Pax-5 (PAX5); proacrosin binding protein sp32 (OY-TES 1); lymphocyte-specific protein tyrosine kinase (LCK); A kinase anchor protein 4 (AKAP-4); synovial sarcoma, X breakpoint 2 (SSX2); Receptor for Advanced Glycation Endproducts (RAGE-1); renal ubiquitous 1 (RU1); renal ubiquitous 2 (RU2); legumain; human papilloma virus E6 (HPV E6); human papilloma virus E7 (HPV E7); intestinal carboxyl esterase; heat shock protein 70-2 mutated (mut hsp70-2); CD79a; CD79b; CD72; Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1); Fc fragment of IgA receptor (FCAR or CD89); Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); CD300 molecule-like family member f (CD300LF); C-type lectin domain family 12 member A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2); lymphocyte antigen 75 (LY75); Glypican-3 (GPC3); Fc receptor-like 5 (FCRL5); and immunoglobulin lambda-like polypeptide 1 (IGLL1).

›GUUGGAACCAUUCAAAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUA · 11 of 12

A CAR described herein can comprise an antigen binding domain (e.g., antibody or antibody fragment, TCR or TCR fragment) that binds to a tumor-supporting antigen (e.g., a tumor-supporting antigen as described herein). In some embodiments, the tumor-supporting antigen is an antigen present on a stromal cell or a myeloid-derived suppressor cell (MDSC). Stromal cells can secrete growth factors to promote cell division in the microenvironment. MDSC cells can inhibit T cell proliferation and activation. Without wishing to be bound by theory, in some embodiments, the CAR-expressing cells destroy the tumor-supporting cells, thereby indirectly inhibiting tumor growth or survival.

In embodiments, the stromal cell antigen is chosen from one or more of: bone marrow stromal cell antigen 2 (BST2), fibroblast activation protein (FAP) and tenascin. In an embodiment, the FAP-specific antibody is, competes for binding with, or has the same CDRs as, sibrotuzumab. In embodiments, the MDSC antigen is chosen from one or more of: CD33, CD1 b, C14, CD15, and CD66b. Accordingly, in some embodiments, the tumor-supporting antigen is chosen from one or more of: bone marrow stromal cell antigen 2 (BST2), fibroblast activation protein (FAP) or tenascin, CD33, CD1 b, C14, CD15, and CD66b.

In some embodiments, more than one CAR gene is inserted into an intron (or intron-exon junction) of the TET2 gene, e.g., sequence encoding a first CAR and sequence encoding a second CAR is inserted into an intron (or intron-exon junction) of the TET2 gene. In embodiments, the sequence encoding the first CAR and the sequence encoding the second CAR are separated by sequence of a 2A site, as described herein. In embodiments, the first CAR is a CD19 CAR and the second CAR is a CD20 CAR or CD22 CAR.

In some embodiments, a CAR gene inserted into an intron of the TET2 gene encodes a CAR comprising two or more antigen binding domains, e.g., two or more antigen binding domains targeting different antigens. Examples of CARs comprising two or more antigen binding domains are described, for example, in WO2016/164731, incorporated herein by reference in its entirety. In embodiments, the first antigen binding domain binds CD19 and the second antigen binding domain binds CD20 or CD22.

In some embodiments, a CAR gene inserted into an intron of the TET2 gene encodes a regulatable CAR gene system. Examplary regulatable CAR systems are described in, for example, WO2017/181119, incorporated herein by reference in its entirety.

In some embodiments, a CAR gene inserted into an intron of the TET2 gene is a CD19 CAR gene. In some embodiments, a CAR gene inserted into an intron of the TET2 gene is a BCMA CAR gene. In some embodiments, a CAR gene inserted into an intron of the TET2 gene is a CD22 CAR gene.

In some embodiments, a CAR gene inserted into an intron between exons 9 and 10 of the TET2 gene is a CD19 CAR gene. In some embodiments, a CAR gene inserted into an intron between exons 9 and 10 of the TET2 gene is a BCMA CAR gene. In some embodiments, a CAR gene inserted into an intron between exons 9 and 10 of the TET2 gene is a CD22 CAR gene.

Antigen-Binding Domain Structures

In some embodiments, the antigen binding domain of the encoded CAR molecule comprises an antibody, an antibody fragment, an scFv, a Fv, a Fab, a (Fab′)2, a single domain antibody (SDAB), a VH and/or VL domain, a camelid VHH domain, a bi-functional (e.g. bi-specific), or multispecific hybrid antibody (e.g., Lanzavecchia et al., Eur. J. Immunol. 17, 105 (1987)).

In some instances, scFvs can be prepared according to method known in the art (see, for example, Bird et al., (1988) Science 242:423-426 and Huston et al., (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883). ScFv molecules can be produced by linking VH and VL regions together using flexible polypeptide linkers. The scFv molecules can comprise a linker (e.g., a Ser-Gly linker) with an optimized length and/or amino acid composition. The linker length can greatly affect how the variable regions of a scFv fold and interact. In fact, if a short polypeptide linker is employed (e.g., between 5-10 amino acids) intrachain folding is prevented. Interchain folding is also required to bring the two variable regions together to form a functional epitope binding site. For examples of linker orientation and size see, e.g., Hollinger et al. 1993 Proc Natl Acad. Sci. U.S.A. 90:6444-6448, U.S. Patent Application Publication Nos. 2005/0100543, 2005/0175606, 2007/0014794, and PCT publication Nos. WO2006/020258 and WO2007/024715, is incorporated herein by reference.

An scFv can comprise a linker of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, or more amino acid residues between its VL and VH regions. The linker sequence may comprise any naturally occurring amino acid. In some embodiments, the linker sequence comprises amino acids glycine and serine. In another embodiment, the linker sequence comprises sets of glycine and serine repeats such as (Gly4Ser)n, where n is a positive integer equal to or greater than 1 (SEQ ID NO: 26). In one embodiment, the linker can be (Gly 4 Ser) 4 (SEQ ID NO:34) or (Gly 4 Ser) 3 (SEQ ID NO:35). Variation in the linker length may retain or enhance activity, giving rise to superior efficacy in activity studies.

In another aspect, the antigen binding domain is a T cell receptor (“TCR”), or a fragment thereof, for example, a single chain TCR (scTCR). Methods to make such TCRs are known in the art. See, e.g., Willemsen R A et al, Gene Therapy 7: 1369-1377 (2000); Zhang T et al, Cancer Gene Ther 11: 487-496 (2004); Aggen et al, Gene Ther. 19(4):365-74 (2012) (references are incorporated herein by its entirety). For example, scTCR can be engineered that contains the Vα and Vβ genes from a T cell clone linked by a linker (e.g., a flexible peptide). This approach is very useful to cancer associated target that itself is intracellular, however, a fragment of such antigen (peptide) is presented on the surface of the cancer cells by MHC.

›GUUGGAACCAUUCAAAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUA · 12 of 12

In certain embodiments, the encoded antigen binding domain has a binding affinity KD of 10 −4 M to 10 −8 M.

In one embodiment, the encoded CAR molecule comprises an antigen binding domain that has a binding affinity KD of 10 −4 M to 10 −8 M, e.g., 10 −5 M to 10 −7 M, e.g., 10 −6 M or 10 −7 M, for the target antigen. In one embodiment, the antigen binding domain has a binding affinity that is at least five-fold, 10-fold, 20-fold, 30-fold, 50-fold, 100-fold or 1,000-fold less than a reference antibody, e.g., an antibody described herein. In one embodiment, the encoded antigen binding domain has a binding affinity at least 5-fold less than a reference antibody (e.g., an antibody from which the antigen binding domain is derived). In one aspect such antibody fragments are functional in that they provide a biological response that can include, but is not limited to, activation of an immune response, inhibition of signal-transduction origination from its target antigen, inhibition of kinase activity, and the like, as will be understood by a skilled artisan.

In one aspect, the antigen binding domain of the CAR is a scFv antibody fragment that is humanized compared to the murine sequence of the scFv from which it is derived.

In one aspect, the antigen binding domain of a CAR of the disclosure (e.g., a scFv) is encoded by a nucleic acid molecule whose sequence has been codon optimized for expression in a mammalian cell. In one aspect, entire CAR construct of the disclosure is encoded by a nucleic acid molecule whose entire sequence has been codon optimized for expression in a mammalian cell. Codon optimization refers to the discovery that the frequency of occurrence of synonymous codons (i.e., codons that code for the same amino acid) in coding DNA is biased in different species. Such codon degeneracy allows an identical polypeptide to be encoded by a variety of nucleotide sequences. A variety of codon optimization methods is known in the art, and include, e.g., methods disclosed in at least U.S. Pat. Nos. 5,786,464 and 6,114,148.

Antigen-Binding Domains (and the Targeted Antigens)

In one embodiment, an antigen binding domain against CD19 is an antigen binding portion, e.g., CDRs, of a CAR, antibody or antigen-binding fragment thereof described in, e.g., PCT publication WO2012/079000; PCT publication WO2014/153270; Kochenderfer, J. N. et al., J. Immunother. 32 (7), 689-702 (2009); Kochenderfer, J. N., et al., Blood, 116 (20), 4099-4102 (2010); PCT publication WO2014/031687; Bejcek, Cancer Research, 55, 2346-2351, 1995; or U.S. Pat. No. 7,446,190.

In one embodiment, an antigen binding domain against mesothelin is an antigen binding portion, e.g., CDRs, of an antibody, antigen-binding fragment or CAR described in, e.g., PCT publication WO2015/090230. In one embodiment, an antigen binding domain against mesothelin is an antigen binding portion, e.g., CDRs, of an antibody, antigen-binding fragment, or CAR described in, e.g., PCT publication WO1997/025068, WO1999/028471, WO2005/014652, WO2006/099141, WO2009/045957, WO2009/068204, WO2013/142034, WO2013/040557, or WO2013/063419. In one embodiment, an antigen binding domain against mesothelin is an antigen binding portion, e.g., CDRs, of an antibody, antigen-binding fragment, or CAR described in WO/2015/090230.

In one embodiment, an antigen binding domain against CD123 is an antigen binding portion, e.g., CDRs, of an antibody, antigen-binding fragment or CAR described in, e.g., PCT publication WO2014/130635. In one embodiment, an antigen binding domain against CD123 is an antigen binding portion, e.g., CDRs, of an antibody, antigen-binding fragment, or CAR described in, e.g., PCT publication WO2014/138805, WO2014/138819, WO2013/173820, WO2014/144622, WO2001/66139, WO2010/126066, WO2014/144622, or US2009/0252742. In one embodiment, an antigen binding domain against CD123 is an antigen binding portion, e.g., CDRs, of an antibody, antigen-binding fragment, or CAR described in WO/2016/028896.

Examples include CAR molecules which include an antigen binding domain, or a VL and VH (in the sequences below, separated by a (G4S)3 linker (SEQ ID NO: 35)) of:

CD123-1:

(SEQ ID NO: 150)

QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWI
NPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDMNI
LATVPFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGD
›RVTITCRASQSISTYLNWYQQKPGKAPNLLIYAAFSLQSGVPSRFSGSGSG

TDFTLTINSLQPEDFATYYCQQGDSVPLTFGGGTKLEIK;

CD123-2:

(SEQ ID NO: 151)

QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWI
NPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNI
LATVPFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGD
›RVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG

TDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIK;

CD123-3:

(SEQ ID NO: 153)

QVQLVQSGAEVKKPGASVKVSCKASGYIFTGYYIHWVRQAPGQGLEWMGWI
NPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSGLRSDDPAVYYCARDMNI
LATVPFDIWGQGTLVTVSSGGGGSGGGGSGGGGSDIQLTQSPSSLSASVGD
›RVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG

TDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTKVEIK;

OR

CD123-4:

(SEQ ID NO: 154)

QVQLQQSGAEVKKSGASVKVSCKASGYTFTDYYMEIWLRQAPGQGLEWMGW
INPNSGDTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMN
ILATVPFDIWGQGTMVTVSSASGGGGSGGRASGGGGSDIQMTQSPSSLSAS
›VGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGS

GSGTDFTLTISSLQPEDFATYYCQQGDSVPLTFGGGTKVEIK,

from WO2016/0028896.

The CAR comprising said anti-CD123 binding domain may comprise, for example, the amino acid sequence of:

CAR123-2:

(SEQ ID NO: 155)

MALPVTALLLPLALLLHAARPQVQLVQSGAEVKKPGASVKVSCKASGYTFT
GYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYM
ELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSGGGGSGGGGSG
GGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLL
IYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTF
GGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDF
ACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQE
EDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYD
›VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGK

GHDGLYQGLSTATKDTYDALHMQALPPR;

CAR123-3:

(SEQ ID NO: 156)

MALPVTALLLPLALLLHAARPQVQLVQSGAEVKKPGASVKVSCKASGYIFT
GYYIHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSISTAYM
ELSGLRSDDPAVYYCARDMNILATVPFDIWGQGTLVTVSSGGGGSGGGGSG
GGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLL
IYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTF
GGGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDF
ACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQE
EDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYD
›VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGK

GHDGLYQGLSTATKDTYDALHMQALPPR;

CAR123-4:

(SEQ ID NO: 157)

MALPVTALLLPLALLLHAARPQVQLQQSGAEVKKSGASVKVSCKASGYTFT
DYYMHWLRQAPGQGLEWMGWINPNSGDTNYAQKFQGRVTLTRDTSISTVYM
ELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSASGGGGSGGRA
SGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPK
LLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGDSVPL
›TFGGGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGL

DFACDIYIWAPLAGTCGVLLLSLVITLYCK;

OR

CAR123-1:

(SEQ ID NO: 158)

MALPVTALLLPLALLLHAARPQVQLVQSGAEVKKPGASVKVSCKASGYTFT
GYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSISTAYM
ELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSGGGGSGGGGSG
GGGSDIQMTQSPSSLSASVGDRVTITCRASQSISTYLNWYQQKPGKAPNLL
IYAAFSLQSGVPSRFSGSGSGTDFTLTINSLQPEDFATYYCQQGDSVPLTF
GGGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDF
ACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQE
EDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYD
›VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGK · 1 of 9

GHDGLYQGLSTATKDTYDALHMQALPPR.

In each case, the CAR may optionally comprise or not comprise the leader sequence included in each of the above sequences (MALPVTALLLPLALLLHAARP; SEQ ID NO: 2).

In one embodiment, an antigen binding domain against EGFRvIII is an antigen binding portion, e.g., CDRs, of an antibody, antigen-binding fragment or CAR described in, e.g., WO/2014/130657.

In one embodiment, an antigen binding domain against CD22 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Haso et al., Blood, 121(7): 1165-1174 (2013); Wayne et al., Clin Cancer Res 16(6): 1894-1903 (2010); Kato et al., Leuk Res 37(1):83-88 (2013); Creative BioMart (creativebiomart.net): MOM-18047-S(P).

In one embodiment, an antigen binding domain against CS-1 is an antigen binding portion, e.g., CDRs, of Elotuzumab (BMS), see e.g., Tai et al., 2008, Blood 112(4):1329-37; Tai et al., 2007 , Blood. 110(5): 1656-63.

In one embodiment, an antigen binding domain against CLL-1 is an antigen binding portion, e.g., CDRs, of an antibody available from R&D, ebiosciences, Abcam, for example, PE-CLL1-hu Cat #353604 (BioLegend); and PE-CLL1 (CLEC12A) Cat #562566 (BD). In one embodiment, an antigen binding domain against CLL-1 is an antigen binding portion, e.g., CDRs, of an antibody, antigen-binding fragment, or CAR described in WO/2016/014535.

In one embodiment, an antigen binding domain against CD33 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Bross et al., Clin Cancer Res 7(6): 1490-1496 (2001) (Gemtuzumab Ozogamicin, hP67.6), Caron et al., Cancer Res 52(24):6761-6767 (1992) (Lintuzumab, HuM195), Lapusan et al., Invest New Drugs 30(3):1121-1131 (2012) (AVE9633), Aigner et al., Leukemia 27(5): 1107-1115 (2013) (AMG330, CD33 BiTE), Dutour et al., Adv hematol 2012:683065 (2012), and Pizzitola et al., Leukemia doi:10.1038/Lue.2014.62 (2014). In one embodiment, an antigen binding domain against CD33 is an antigen binding portion, e.g., CDRs, of an antibody, antigen-binding fragment, or CAR described in WO/2016/014576.

In one embodiment, an antigen binding domain against GD2 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Mujoo et al., Cancer Res. 47(4):1098-1104 (1987); Cheung et al., Cancer Res 45(6):2642-2649 (1985), Cheung et al., J Clin Oncol 5(9):1430-1440 (1987), Cheung et al., J Clin Oncol 16(9):3053-3060 (1998), Handgretinger et al., Cancer Immunol Immunother 35(3): 199-204 (1992). In some embodiments, an antigen binding domain against GD2 is an antigen binding portion of an antibody selected from mAb 14.18, 14G2a, ch14.18, hu14.18, 3F8, hu3F8, 3G6, 8B6, 60C3, 10B8, ME36.1, and 8H9, see e.g., WO2012033885, WO2013040371, WO2013192294, WO2013061273, WO2013123061, WO2013074916, and WO201385552. In some embodiments, an antigen binding domain against GD2 is an antigen binding portion of an antibody described in US Publication No.: 20100150910 or PCT Publication No.: WO 2011160119.

In one embodiment, an antigen binding domain against BCMA is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., WO2012163805, WO200112812, and WO2003062401. In one embodiment, an antigen binding domain against BCMA is an antigen binding portion, e.g., CDRs, of an antibody, antigen-binding fragment, or CAR described in WO/2016/014565.

In one embodiment, an antigen binding domain against Tn antigen is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., U.S. Pat. No. 8,440,798, Brooks et al., PNAS 107(22):10056-10061 (2010), and Stone et al., Oncolmmunology 1(6):863-873(2012).

In one embodiment, an antigen binding domain against PSMA is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Parker et al., Protein Expr Purif 89(2):136-145 (2013), US 20110268656 (J591 ScFv); Frigerio et al, European J Cancer 49(9):2223-2232 (2013) (scFvD2B); WO 2006125481 (mAbs 3/A12, 3/E7 and 3/F11) and single chain antibody fragments (scFv A5 and D7).

In one embodiment, an antigen binding domain against ROR1 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Hudecek et al., Clin Cancer Res 19(12):3153-3164 (2013); WO 2011159847; and US20130101607.

In one embodiment, an antigen binding domain against FLT3 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., WO2011076922, U.S. Pat. No. 5,777,084, EP0754230, US20090297529, and several commercial catalog antibodies (R&D, ebiosciences, Abcam).

In one embodiment, an antigen binding domain against TAG72 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Hombach et al., Gastroenterology 113(4):1163-1170 (1997); and Abcam ab691.

In one embodiment, an antigen binding domain against FAP is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Ostermann et al., Clinical Cancer Research 14:4584-4592 (2008) (FAPS), US Pat. Publication No. 2009/0304718; sibrotuzumab (see e.g., Hofheinz et al., Oncology Research and Treatment 26(1), 2003); and Tran et al., J Exp Med 210(6):1125-1135 (2013).

In one embodiment, an antigen binding domain against CD38 is an antigen binding portion, e.g., CDRs, of daratumumab (see, e.g., Groen et al., Blood 116(21):1261-1262 (2010); MOR202 (see, e.g., U.S. Pat. No. 8,263,746); or antibodies described in U.S. Pat. No. 8,362,211.

In one embodiment, an antigen binding domain against CD44v6 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Casucci et al., Blood 122(20):3461-3472 (2013).

In one embodiment, an antigen binding domain against CEA is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Chmielewski et al., Gastoenterology 143(4):1095-1107 (2012).

In one embodiment, an antigen binding domain against EPCAM is an antigen binding portion, e.g., CDRS, of an antibody selected from MT110, EpCAM-CD3 bispecific Ab (see, e.g., clinicaltrials.gov/ct2/show/NCT00635596); Edrecolomab; 3622W94; ING-1; and adecatumumab (MT201).

In one embodiment, an antigen binding domain against PRSS21 is an antigen binding portion, e.g., CDRs, of an antibody described in U.S. Pat. No. 8,080,650.

›VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGK · 2 of 9

In one embodiment, an antigen binding domain against B7H3 is an antigen binding portion, e.g., CDRs, of an antibody MGA271 (Macrogenics).

In one embodiment, an antigen binding domain against KIT is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., U.S. Pat. No. 7,915,391, US20120288506, and several commercial catalog antibodies.

In one embodiment, an antigen binding domain against IL-13Ra2 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., WO2008/146911, WO2004087758, several commercial catalog antibodies, and WO2004087758.

In one embodiment, an antigen binding domain against CD30 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., U.S. Pat. No. 7,090,843 B1, and EP0805871.

In one embodiment, an antigen binding domain against GD3 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., U.S. Pat. Nos. 7,253,263; 8,207,308; US 20120276046; EP1013761; WO2005035577; and U.S. Pat. No. 6,437,098.

In one embodiment, an antigen binding domain against CD171 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Hong et al., J Immunother 37(2):93-104 (2014).

In one embodiment, an antigen binding domain against IL-11Ra is an antigen binding portion, e.g., CDRs, of an antibody available from Abcam (cat # ab55262) or Novus Biologicals (cat # EPR5446). In another embodiment, an antigen binding domain again IL-11Ra is a peptide, see, e.g., Huang et al., Cancer Res 72(1):271-281 (2012).

In one embodiment, an antigen binding domain against PSCA is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Morgenroth et al., Prostate 67(10):1121-1131 (2007) (scFv 7F5); Nejatollahi et al., J of Oncology 2013(2013), article ID 839831 (scFv C5-II); and US Pat Publication No. 20090311181.

In one embodiment, an antigen binding domain against VEGFR2 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Chinnasamy et al., J Clin Invest 120(11):3953-3968 (2010).

In one embodiment, an antigen binding domain against LewisY is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Kelly et al., Cancer Biother Radiopharm 23(4):411-423 (2008) (hu3S193 Ab (scFvs)); Dolezal et al., Protein Engineering 16(1):47-56 (2003) (NC10 scFv).

In one embodiment, an antigen binding domain against CD24 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Maliar et al., Gastroenterology 143(5):1375-1384 (2012).

In one embodiment, an antigen binding domain against PDGFR-beta is an antigen binding portion, e.g., CDRs, of an antibody Abcam ab32570.

In one embodiment, an antigen binding domain against SSEA-4 is an antigen binding portion, e.g., CDRs, of antibody MC813 (Cell Signaling), or other commercially available antibodies.

In one embodiment, an antigen binding domain against CD20 is an antigen binding portion, e.g., CDRs, of the antibody Rituximab, Ofatumumab, Ocrelizumab, Veltuzumab, or GA101.

In one embodiment, an antigen binding domain against Folate receptor alpha is an antigen binding portion, e.g., CDRs, of the antibody IMGN853, or an antibody described in US20120009181; U.S. Pat. No. 4,851,332, LK26: U.S. Pat. No. 5,952,484.

In one embodiment, an antigen binding domain against ERBB2 (Her2/neu) is an antigen binding portion, e.g., CDRs, of the antibody trastuzumab, or pertuzumab.

In one embodiment, an antigen binding domain against MUC1 is an antigen binding portion, e.g., CDRs, of the antibody SAR566658.

In one embodiment, the antigen binding domain against EGFR is antigen binding portion, e.g., CDRs, of the antibody cetuximab, panitumumab, zalutumumab, nimotuzumab, or matuzumab.

In one embodiment, an antigen binding domain against NCAM is an antigen binding portion, e.g., CDRs, of the antibody clone 2-2B: MAB5324 (EMD Millipore).

In one embodiment, an antigen binding domain against Ephrin B2 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Abengozar et al., Blood 119(19):4565-4576 (2012).

In one embodiment, an antigen binding domain against IGF-I receptor is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., U.S. Pat. No. 8,344,112 B2; EP2322550 A1; WO 2006/138315, or PCT/US2006/022995.

In one embodiment, an antigen binding domain against CAIX is an antigen binding portion, e.g., CDRs, of the antibody clone 303123 (R&D Systems).

In one embodiment, an antigen binding domain against LMP2 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., U.S. Pat. No. 7,410,640, or US20050129701.

In one embodiment, an antigen binding domain against gp100 is an antigen binding portion, e.g., CDRs, of the antibody HMB45, NKIbetaB, or an antibody described in WO2013165940, or US20130295007

In one embodiment, an antigen binding domain against tyrosinase is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., U.S. Pat. No. 5,843,674; or U.S. Ser. No. 19/950,504048.

In one embodiment, an antigen binding domain against EphA2 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Yu et al., Mol Ther 22(1):102-111 (2014).

In one embodiment, an antigen binding domain against GD3 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., U.S. Pat. Nos. 7,253,263; 8,207,308; US 20120276046; EP1013761 A3; 20120276046; WO2005035577; or U.S. Pat. No. 6,437,098.

In one embodiment, an antigen binding domain against fucosyl GM1 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., US20100297138; or WO2007/067992.

In one embodiment, an antigen binding domain against sLe is an antigen binding portion, e.g., CDRs, of the antibody G193 (for lewis Y), see Scott A M et al, Cancer Res 60: 3254-61 (2000), also as described in Neeson et al, J Immunol May 2013 190 (Meeting Abstract Supplement) 177.10.

In one embodiment, an antigen binding domain against GM3 is an antigen binding portion, e.g., CDRs, of the antibody CA 2523449 (mAb 14F7).

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In one embodiment, an antigen binding domain against HMWMAA is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Kmiecik et al., Oncoimmunology 3(1):e27185 (2014) (PMID: 24575382) (mAb9.2.27); U.S. Pat. No. 6,528,481; WO2010033866; or US 20140004124.

In one embodiment, an antigen binding domain against o-acetyl-GD2 is an antigen binding portion, e.g., CDRs, of the antibody 8B6.

In one embodiment, an antigen binding domain against TEM1/CD248 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Marty et al., Cancer Lett 235(2):298-308 (2006); Zhao et al., J Immunol Methods 363(2):221-232 (2011).

In one embodiment, an antigen binding domain against CLDN6 is an antigen binding portion, e.g., CDRs, of the antibody IMABO27 (Ganymed Pharmaceuticals), see e.g., clinicaltrial.gov/show/NCT02054351.

In one embodiment, an antigen binding domain against TSHR is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., U.S. Pat. Nos. 8,603,466; 8,501,415; or U.S. Pat. No. 8,309,693.

In one embodiment, an antigen binding domain against GPRC5D is an antigen binding portion, e.g., CDRs, of the antibody FAB6300A (R&D Systems); or LS-A4180 (Lifespan Biosciences).

In one embodiment, an antigen binding domain against CD97 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., U.S. Pat. No. 6,846,911; de Groot et al., J Immunol 183(6):4127-4134 (2009); or an antibody from R&D:MAB3734.

In one embodiment, an antigen binding domain against ALK is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Mino-Kenudson et al., Clin Cancer Res 16(5):1561-1571 (2010).

In one embodiment, an antigen binding domain against polysialic acid is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Nagae et al., J Biol Chem 288(47):33784-33796 (2013).

In one embodiment, an antigen binding domain against PLAC1 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Ghods et al., Biotechnol Appl Biochem 2013 doi:10.1002/bab.1177.

In one embodiment, an antigen binding domain against GloboH is an antigen binding portion of the antibody VK9; or an antibody described in, e.g., Kudryashov V et al, Glycoconj J.15(3):243-9 (1998), Lou et al., Proc Natl Acad Sci USA 111(7):2482-2487 (2014); MBrl: Bremer E-G et al. J Biol Chem 259:14773-14777 (1984).

In one embodiment, an antigen binding domain against NY-BR-1 is an antigen binding portion, e.g., CDRs of an antibody described in, e.g., Jager et al., Appl Immunohistochem Mol Morphol 15(1):77-83 (2007).

In one embodiment, an antigen binding domain against WT-1 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Dao et al., Sci Transl Med 5(176):176ra33 (2013); or WO2012/135854.

In one embodiment, an antigen binding domain against MAGE-A1 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Willemsen et al., J Immunol 174(12):7853-7858 (2005) (TCR-like scFv).

In one embodiment, an antigen binding domain against sperm protein 17 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Song et al., Target Oncol 2013 Aug. 14 (PMID: 23943313); Song et al., Med Oncol 29(4):2923-2931 (2012).

In one embodiment, an antigen binding domain against Tie 2 is an antigen binding portion, e.g., CDRs, of the antibody AB33 (Cell Signaling Technology).

In one embodiment, an antigen binding domain against MAD-CT-2 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., PMID: 2450952; U.S. Pat. No. 7,635,753.

In one embodiment, an antigen binding domain against Fos-related antigen 1 is an antigen binding portion, e.g., CDRs, of the antibody 12F9 (Novus Biologicals).

In one embodiment, an antigen binding domain against MelanA/MART1 is an antigen binding portion, e.g., CDRs, of an antibody described in, EP2514766 A2; or U.S. Pat. No. 7,749,719.

In one embodiment, an antigen binding domain against sarcoma translocation breakpoints is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Luo et al, EMBO Mol. Med. 4(6):453-461 (2012).

In one embodiment, an antigen binding domain against TRP-2 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Wang et al, J Exp Med. 184(6):2207-16 (1996).

In one embodiment, an antigen binding domain against CYP1B1 is an antigen binding portion, e.g., CDRs, of an antibody described in, e.g., Maecker et al, Blood 102 (9): 3287-3294 (2003).

In one embodiment, an antigen binding domain against RAGE-1 is an antigen binding portion, e.g., CDRs, of the antibody MAB5328 (EMD Millipore).

In one embodiment, an antigen binding domain against human telomerase reverse transcriptase is an antigen binding portion, e.g., CDRs, of the antibody cat no: LS-B95-100 (Lifespan Biosciences)

In one embodiment, an antigen binding domain against intestinal carboxyl esterase is an antigen binding portion, e.g., CDRs, of the antibody 4F12: cat no: LS-B6190-50 (Lifespan Biosciences).

In one embodiment, an antigen binding domain against mut hsp70-2 is an antigen binding portion, e.g., CDRs, of the antibody Lifespan Biosciences: monoclonal: cat no: LS-C133261-100 (Lifespan Biosciences).

In one embodiment, an antigen binding domain against CD79a is an antigen binding portion, e.g., CDRs, of the antibody Anti-CD79a antibody [HM47/A9] (ab3121), available from Abcam; antibody CD79A Antibody #3351 available from Cell Signalling Technology; or antibody HPA017748-Anti-CD79A antibody produced in rabbit, available from Sigma Aldrich.

In one embodiment, an antigen binding domain against CD79b is an antigen binding portion, e.g., CDRs, of the antibody polatuzumab vedotin, anti-CD79b described in Dornan et al., “Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma” Blood. 2009 Sep. 24; 114(13):2721-9. doi: 10.1182/blood-2009-02-205500. Epub 2009 Jul. 24, or the bispecific antibody Anti-CD79b/CD3 described in “4507 Pre-Clinical Characterization of T Cell-Dependent Bispecific Antibody Anti-CD79b/CD3 As a Potential Therapy for B Cell Malignancies” Abstracts of 56 th ASH Annual Meeting and Exposition, San Francisco, CA Dec. 6-9, 2014.

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In one embodiment, an antigen binding domain against CD72 is an antigen binding portion, e.g., CDRs, of the antibody J3-109 described in Myers, and Uckun, “An anti-CD72 immunotoxin against therapy-refractory B-lineage acute lymphoblastic leukemia.” Leuk Lymphoma. 1995 June; 18(1-2):119-22, or anti-CD72 (10D6.8.1, mIgGi) described in Polson et al., “Antibody-Drug Conjugates for the Treatment of Non-Hodgkin's Lymphoma: Target and Linker-Drug Selection” Cancer Res Mar. 15, 2009 69; 2358.

In one embodiment, an antigen binding domain against LAIR1 is an antigen binding portion, e.g., CDRs, of the antibody ANT-301 LAIR1 antibody, available from ProSpec; or anti-human CD305 (LAIR1) Antibody, available from BioLegend.

In one embodiment, an antigen binding domain against FCAR is an antigen binding portion, e.g., CDRs, of the antibody CD89/FCAR Antibody (Catalog #10414-H08H), available from Sino Biological Inc.

In one embodiment, an antigen binding domain against LILRA2 is an antigen binding portion, e.g., CDRs, of the antibody LILRA2 monoclonal antibody (M17), clone 3C7, available from Abnova, or Mouse Anti-LILRA2 antibody, Monoclonal (2D7), available from Lifespan Biosciences.

In one embodiment, an antigen binding domain against CD300LF is an antigen binding portion, e.g., CDRs, of the antibody Mouse Anti-CMRF35-like molecule 1 antibody, Monoclonal[UP-D2, available from BioLegend, or Rat Anti-CMRF35-like molecule 1 antibody, Monoclonal[234903], available from R&D Systems.

In one embodiment, an antigen binding domain against CLEC12A is an antigen binding portion, e.g., CDRs, of the antibody Bispecific T cell Engager (BiTE) scFv-antibody and ADC described in Noordhuis et al., “Targeting of CLEC12A In Acute Myeloid Leukemia by Antibody-Drug-Conjugates and Bispecific CLL-1×CD3 BiTE Antibody” 53 rd ASH Annual Meeting and Exposition, Dec. 10-13, 2011, and MCLA-117 (Merus).

In one embodiment, an antigen binding domain against BST2 (also called CD317) is an antigen binding portion, e.g., CDRs, of the antibody Mouse Anti-CD317 antibody, Monoclonal[3H4], available from Antibodies-Online or Mouse Anti-CD317 antibody, Monoclonal [696739], available from R&D Systems.

In one embodiment, an antigen binding domain against EMR2 (also called CD312) is an antigen binding portion, e.g., CDRs, of the antibody Mouse Anti-CD312 antibody, Monoclonal[LS-B8033] available from Lifespan Biosciences, or Mouse Anti-CD312 antibody, Monoclonal [494025] available from R&D Systems.

In one embodiment, an antigen binding domain against LY75 is an antigen binding portion, e.g., CDRs, of the antibody Mouse Anti-Lymphocyte antigen 75 antibody, Monoclonal[HD30] available from EMD Millipore or Mouse Anti-Lymphocyte antigen 75 antibody, Monoclonal[A15797] available from Life Technologies.

In one embodiment, an antigen binding domain against GPC3 is an antigen binding portion, e.g., CDRs, of the antibody hGC33 described in Nakano K, Ishiguro T, Konishi H, et al. Generation of a humanized anti-glypican 3 antibody by CDR grafting and stability optimization. Anticancer Drugs. 2010 November; 21(10):907-916, or MDX-1414, HN3, or YP7, all three of which are described in Feng et al., “Glypican-3 antibodies: a new therapeutic target for liver cancer.” FEBS Lett. 2014 Jan. 21; 588(2):377-82.

In one embodiment, an antigen binding domain against FCRL5 is an antigen binding portion, e.g., CDRs, of the anti-FcRL5 antibody described in Elkins et al., “FcRL5 as a target of antibody-drug conjugates for the treatment of multiple myeloma” Mol Cancer Ther. 2012 October; 11(10):2222-32. In one embodiment, an antigen binding domain against FCRL5 is an antigen binding portion, e.g., CDRs, of the anti-FcRL5 antibody described in, for example, WO2001/038490, WO/2005/117986, WO2006/039238, WO2006/076691, WO2010/114940, WO2010/120561, or WO2014/210064.

In one embodiment, an antigen binding domain against IGLL1 is an antigen binding portion, e.g., CDRs, of the Mouse Anti-Immunoglobulin lambda-like polypeptide 1 antibody, Monoclonal[AT1G4] available from Lifespan Biosciences, Mouse Anti-Immunoglobulin lambda-like polypeptide 1 antibody, Monoclonal[HSL11] available from BioLegend.

In one embodiment, the antigen binding domain comprises one, two, or three (e.g., all three) heavy chain CDRs, HC CDR1, HC CDR2 and HC CDR3, from an antibody listed above, and/or one, two, or three (e.g., all three) light chain CDRs, LC CDR1, LC CDR2 and LC CDR3, from an antibody listed above. In one embodiment, the antigen binding domain comprises a heavy chain variable region and/or a variable light chain region of an antibody listed above. In some embodiments, the CAR comprises an antigen-binding domain and an Fc region as described herein.

In another aspect, the antigen binding domain comprises a humanized antibody or an antibody fragment. In some aspects, a non-human antibody is humanized, where specific sequences or regions of the antibody are modified to increase similarity to an antibody naturally produced in a human or fragment thereof. In one aspect, the antigen binding domain is humanized. In some embodiments, a non-human antibody or fragment is humanized and back-mutated to bring the antigen binding affinity of the humanized antibody closer to that of the original non-human antibody or fragment.

In an embodiment, the antigen-binding domain of a CAR, e.g., a CAR expressed by a cell binds to CD19. CD19 is found on B cells throughout differentiation of the lineage from the pro/pre-B cell stage through the terminally differentiated plasma cell stage. In an embodiment, the antigen binding domain comprises a murine scFv domain that binds to human CD19, e.g., the antigen binding domain of CTL019 (e.g., SEQ ID NO: 160). In an embodiment, the antigen binding domain comprises a humanized antibody or antibody fragment, e.g., a scFv domain, derived from the murine CTL019 scFv. In an embodiment, the antigen binding domain is a human antibody or antibody fragment that binds to human CD19. Exemplary scFv domains (and their sequences, e.g., CDRs, VL and VH sequences) that bind to CD19 are provided in Table 4. The scFv domain sequences provided in Table 4 include a light chain variable region (VL) and a heavy chain variable region (VH). The VL and VH are attached by a linker comprising the sequence GGGGSGGGGSGGGGS (SEQ ID NO: 35), e.g., in the following orientation: VL-linker-VH.

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The sequences of the CDR sequences of the scFv domains of the CD19 antigen binding domains provided in Table 4 are shown in Table 5 for the heavy chain variable domains and in Table 6 for the light chain variable domains. “ID” stands for the respective SEQ ID NO for each CDR.

In an embodiment, the antigen binding domain comprises an anti-CD19 antibody, or fragment thereof, e.g., an scFv. For example, the antigen binding domain comprises a variable heavy chain and/or a variable light chain listed in Table 7. The linker sequence joining the variable heavy and variable light chains can be any of the linker sequences described herein, or alternatively, can be GSTSGSGKPGSGEGSTKG (SEQ ID NO: 38). The light chain variable region and heavy chain variable region of a scFv can be, e.g., in any of the following orientations: light chain variable region-linker-heavy chain variable region or heavy chain variable region-linker-light chain variable region.

In one embodiment, the CD19 binding domain comprises one or more (e.g., all three) light chain complementary determining region 1 (LC CDR1), light chain complementary determining region 2 (LC CDR2), and light chain complementary determining region 3 (LC CDR3) of a CD19 binding domain described herein, e.g., provided in Table 4 or 6, and/or one or more (e.g., all three) heavy chain complementary determining region 1 (HC CDR1), heavy chain complementary determining region 2 (HC CDR2), and heavy chain complementary determining region 3 (HC CDR3) of a CD19 binding domain described herein, e.g., provided in Table 4 or 5. In one embodiment, the CD19 binding domain comprises one, two, or all of LC CDR1, LC CDR2, and LC CDR3 of any amino acid sequences as provided in Table 6, incorporated herein by reference; and one, two or all of HC CDR1, HC CDR2, and HC CDR3 of any amino acid sequences as provided in Table 5.

In one embodiment, the CD19 antigen binding domain comprises:

(i) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 182, a LC CDR2 amino acid sequence of SEQ ID NO: 183, and a LC CDR3 amino acid sequence of SEQ ID NO: 184; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 176, a HC CDR2 amino acid sequence of SEQ ID NO: 177, and a HC CDR3 amino acid sequence of SEQ ID NO: 181

(ii) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 182, a LC CDR2 amino acid sequence of SEQ ID NO: 183, and a LC CDR3 amino acid sequence of SEQ ID NO: 184; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 176, a HC CDR2 amino acid sequence of SEQ ID NO: 178, and a HC CDR3 amino acid sequence of SEQ ID NO: 181;

(iii) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 182, a LC CDR2 amino acid sequence of SEQ ID NO: 183, and a LC CDR3 amino acid sequence of SEQ ID NO: 184; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 176, a HC CDR2 amino acid sequence of SEQ ID NO: 179, and a HC CDR3 amino acid sequence of SEQ ID NO: 181; or

(iv) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 182, a LC CDR2 amino acid sequence of SEQ ID NO: 183, and a LC CDR3 amino acid sequence of SEQ ID NO: 184; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 176, a HC CDR2 amino acid sequence of SEQ ID NO: 180, and a HC CDR3 amino acid sequence of SEQ ID NO: 181.

In one embodiment, the CD19 binding domain comprises a light chain variable region described herein (e.g., in Table 4 or 7) and/or a heavy chain variable region described herein (e.g., in Table 4 or 7). In one embodiment, the CD19 binding domain is a scFv comprising a light chain and a heavy chain of an amino acid sequence listed in Table 4 or 7. In an embodiment, the CD19 binding domain (e.g., an scFv) comprises: a light chain variable region comprising an amino acid sequence having at least one, two or three modifications (e.g., substitutions, e.g., conservative substitutions) but not more than 30, 20 or 10 modifications (e.g., substitutions, e.g., conservative substitutions) of an amino acid sequence of a light chain variable region provided in Table 4 or 7, or a sequence with 95-99% identity with an amino acid sequence provided in Table 4 or 7; and/or a heavy chain variable region comprising an amino acid sequence having at least one, two or three modifications (e.g., substitutions, e.g., conservative substitutions) but not more than 30, 20 or 10 modifications (e.g., substitutions, e.g., conservative substitutions) of an amino acid sequence of a heavy chain variable region provided in Table 4 or 7, or a sequence with 95-99% identity to an amino acid sequence provided in Table 4 or 7.

In one embodiment, the CD19 binding domain comprises an amino acid sequence selected from a group consisting of SEQ ID NO: 161; SEQ ID NO: 162, SEQ ID NO: 163; SEQ ID NO: 164; SEQ ID NO: 165; SEQ ID NO: 166; SEQ ID NO: 167, SEQ ID NO: 168, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 160, and SEQ ID NO: 175; or an amino acid sequence having at least one, two or three modifications (e.g., substitutions, e.g., conservative substitutions) but not more than 30, 20 or 10 modifications (e.g., substitutions, e.g., conservative substitutions) to any of the aforesaid sequences; or a sequence with 95-99% identity to any of the aforesaid sequences. In one embodiment, the CD19 binding domain is a scFv, and a light chain variable region comprising an amino acid sequence described herein, e.g., in Table 4 or 7, is attached to a heavy chain variable region comprising an amino acid sequence described herein, e.g., in Table 4 or 7, via a linker, e.g., a linker described herein. In one embodiment, the CD19 binding domain includes a (Gly4-Ser)n linker, wherein n is 1, 2, 3, 4, 5, or 6 (SEQ ID NO: 10561), preferably 3 (SEQ ID NO: 35). The light chain variable region and heavy chain variable region of a scFv can be, e.g., in any of the following orientations: light chain variable region-linker-heavy chain variable region or heavy chain variable region-linker-light chain variable region.

Any known CD19 CAR, e.g., the CD19 antigen binding domain of any known CD19 CAR, in the art can be used in accordance with the instant disclosure to construct a CAR. For example, LG-740; CD19 CAR described in the U.S. Pat. Nos. 8,399,645; 7,446,190; Xu et al., Leuk Lymphoma. 2013 54(2):255-260(2012); Cruz et al., Blood 122(17):2965-2973 (2013); Brentjens et al., Blood, 118(18):4817-4828 (2011); Kochenderfer et al., Blood 116(20):4099-102 (2010); Kochenderfer et al., Blood 122 (25):4129-39(2013); and 16th Annu Meet Am Soc Gen Cell Ther (ASGCT) (May 15-18, Salt Lake City) 2013, Abst 10. In one embodiment, an antigen binding domain against CD19 comprises an antigen binding portion, e.g., the CDRs, of a CAR, antibody or antigen-binding fragment thereof described in, e.g., PCT publication WO2012/079000; PCT publication WO2014/153270; Kochenderfer, J. N. et al., J. Immunother. 32 (7), 689-702 (2009); Kochenderfer, J. N., et al., Blood, 116 (20), 4099-4102 (2010); PCT publication WO2014/031687; Bejcek, Cancer Research, 55, 2346-2351, 1995; or U.S. Pat. No. 7,446,190.

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In an embodiment, the antigen-binding domain of CAR, e.g., a CAR expressed by a cell of the disclosure, binds to BCMA. BCMA is found preferentially expressed in mature B lymphocytes. In an embodiment, the antigen binding domain is a murine scFv domain that binds to human BCMA. In an embodiment, the antigen binding domain is a humanized antibody or antibody fragment, e.g., scFv domain, that binds human BCMA. In an embodiment, the antigen binding domain is a humanized and back-mutated antibody or antibody fragment, e.g., scFv domain, that binds human BCMA. In an embodiment, the antigen binding domain is a human antibody or antibody fragment that binds to human BCMA. Exemplary scFv domains (and their sequences, e.g., CDRs, VL and VH sequences) that bind to BCMA are provided in Table 8, Table 9, Table 10 and Table 11. The scFv domain sequences provided in Table 8 and Table 9 include a light chain variable region (VL) and a heavy chain variable region (VH). The VL and VH are attached by a linker, e.g., in the following orientation: VH-linker-VL.

In embodiments, additional exemplary BCMA CAR constructs are generated using the CDR and/or VH and VL sequences from PCT Publication WO2012/0163805 (the contents of which are hereby incorporated by reference in its entirety). In embodiments, additional exemplary BCMA CAR constructs are generated using the CDR and/or VH and VL sequences from PCT Publication WO2016/014565 (the contents of which are hereby incorporated by reference in its entirety). In embodiments, additional exemplary BCMA CAR constructs are generated using the CDR and/or VH and VL sequences from PCT Publication WO2014/122144 (the contents of which are hereby incorporated by reference in its entirety). In embodiments, additional exemplary BCMA CAR constructs are generated using the CAR molecules, and/or the VH and VL sequences from PCT Publication WO2016/014789 (the contents of which are hereby incorporated by reference in its entirety). In embodiments, additional exemplary BCMA CAR constructs are generated using the CAR molecules, and/or the VH and VL sequences from PCT Publication WO2014/089335 (the contents of which are hereby incorporated by reference in its entirety). In embodiments, additional exemplary BCMA CAR constructs are generated using the CAR molecules, and/or the VH and VL sequences from PCT Publication WO2014/140248 (the contents of which are hereby incorporated by reference in its entirety).

In embodiments, additional exemplary BCMA CAR constructs can also be generated using the VH and VL sequences found in Table 9. The amino acid sequences of exemplary scFv domains comprising the VH and VL domains and a linker sequence, and full-length CARs, are in Table 9.

The sequences of human CDR sequences of the scFv domains are shown in Table 10 for the heavy chain variable domains and in Table 11 for the light chain variable domains. “ID” stands for the respective SEQ ID NO for each CDR. The CDRs are shown according to the Kabat definition, however, the CDRs under other convention, for example, Chothia or the combined Kabat/Chothia definitions may be readily deduced based on the VH and VL sequences above.

In one embodiment, the BCMA binding domain comprises one or more (e.g., all three) light chain complementary determining region 1 (LC CDR1), light chain complementary determining region 2 (LC CDR2), and light chain complementary determining region 3 (LC CDR3) of a BCMA binding domain described herein, e.g., provided in Table 8, 9 or 11, and/or one or more (e.g., all three) heavy chain complementary determining region 1 (HC CDR1), heavy chain complementary determining region 2 (HC CDR2), and heavy chain complementary determining region 3 (HC CDR3) of a BCMA binding domain described herein, e.g., provided in Table 8, 9 or 10. In one embodiment, the BCMA binding domain comprises one, two, or all of LC CDR1, LC CDR2, and LC CDR3 of any amino acid sequences as provided in Table 8; and one, two or all of HC CDR1, HC CDR2, and HC CDR3 of any amino acid sequences as provided in Table 8.

In one embodiment, the BCMA antigen binding domain comprises:

(i) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 714, a LC CDR2 amino acid sequence of SEQ ID NO: 754, and a LC CDR3 amino acid sequence of SEQ ID NO: 794; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 594, a HC CDR2 amino acid sequence of SEQ ID NO: 634, and a HC CDR3 amino acid sequence of SEQ ID NO: 674

(ii) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 704, a LC CDR2 amino acid sequence of SEQ ID NO: 744, and a LC CDR3 amino acid sequence of SEQ ID NO: 784; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 584, a HC CDR2 amino acid sequence of SEQ ID NO: 624, and a HC CDR3 amino acid sequence of SEQ ID NO: 664

(iii) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 705, a LC CDR2 amino acid sequence of SEQ ID NO: 745, and a LC CDR3 amino acid sequence of SEQ ID NO: 785; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 585, a HC CDR2 amino acid sequence of SEQ ID NO: 625, and a HC CDR3 amino acid sequence of SEQ ID NO: 665

(iv) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 706, a LC CDR2 amino acid sequence of SEQ ID NO: 746, and a LC CDR3 amino acid sequence of SEQ ID NO: 786; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 586, a HC CDR2 amino acid sequence of SEQ ID NO: 626, and a HC CDR3 amino acid sequence of SEQ ID NO: 666

(v) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 707, a LC CDR2 amino acid sequence of SEQ ID NO: 747, and a LC CDR3 amino acid sequence of SEQ ID NO: 787; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 587, a HC CDR2 amino acid sequence of SEQ ID NO: 627, and a HC CDR3 amino acid sequence of SEQ ID NO: 667

(vi) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 708, a LC CDR2 amino acid sequence of SEQ ID NO: 748, and a LC CDR3 amino acid sequence of SEQ ID NO: 788; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 588, a HC CDR2 amino acid sequence of SEQ ID NO: 628, and a HC CDR3 amino acid sequence of SEQ ID NO: 668

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(vii) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 709, a LC CDR2 amino acid sequence of SEQ ID NO: 749, and a LC CDR3 amino acid sequence of SEQ ID NO: 789; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 589, a HC CDR2 amino acid sequence of SEQ ID NO: 629, and a HC CDR3 amino acid sequence of SEQ ID NO: 669

(viii) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 710, a LC CDR2 amino acid sequence of SEQ ID NO: 750, and a LC CDR3 amino acid sequence of SEQ ID NO: 790; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 590, a HC CDR2 amino acid sequence of SEQ ID NO: 630, and a HC CDR3 amino acid sequence of SEQ ID NO: 670

(ix) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 711, a LC CDR2 amino acid sequence of SEQ ID NO: 751, and a LC CDR3 amino acid sequence of SEQ ID NO: 791; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 591, a HC CDR2 amino acid sequence of SEQ ID NO: 631, and a HC CDR3 amino acid sequence of SEQ ID NO: 671

(x) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 712, a LC CDR2 amino acid sequence of SEQ ID NO: 752, and a LC CDR3 amino acid sequence of SEQ ID NO: 792; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 592, a HC CDR2 amino acid sequence of SEQ ID NO: 632, and a HC CDR3 amino acid sequence of SEQ ID NO: 672

(xi) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 713, a LC CDR2 amino acid sequence of SEQ ID NO: 753, and a LC CDR3 amino acid sequence of SEQ ID NO: 793; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 593, a HC CDR2 amino acid sequence of SEQ ID NO: 633, and a HC CDR3 amino acid sequence of SEQ ID NO: 673

(xii) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 715, a LC CDR2 amino acid sequence of SEQ ID NO: 755, and a LC CDR3 amino acid sequence of SEQ ID NO: 795; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 595, a HC CDR2 amino acid sequence of SEQ ID NO: 635, and a HC CDR3 amino acid sequence of SEQ ID NO: 675

(xiii) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 716, a LC CDR2 amino acid sequence of SEQ ID NO: 756, and a LC CDR3 amino acid sequence of SEQ ID NO: 796; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 596, a HC CDR2 amino acid sequence of SEQ ID NO: 636, and a HC CDR3 amino acid sequence of SEQ ID NO: 676

(xiv) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 717, a LC CDR2 amino acid sequence of SEQ ID NO: 757, and a LC CDR3 amino acid sequence of SEQ ID NO: 797; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 597, a HC CDR2 amino acid sequence of SEQ ID NO: 637, and a HC CDR3 amino acid sequence of SEQ ID NO: 677

(xv) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 718, a LC CDR2 amino acid sequence of SEQ ID NO: 758, and a LC CDR3 amino acid sequence of SEQ ID NO: 798; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 598, a HC CDR2 amino acid sequence of SEQ ID NO: 638, and a HC CDR3 amino acid sequence of SEQ ID NO: 678

(xvi) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 719, a LC CDR2 amino acid sequence of SEQ ID NO: 759, and a LC CDR3 amino acid sequence of SEQ ID NO: 799; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 599, a HC CDR2 amino acid sequence of SEQ ID NO: 639, and a HC CDR3 amino acid sequence of SEQ ID NO: 679

(xvii) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 720, a LC CDR2 amino acid sequence of SEQ ID NO: 760, and a LC CDR3 amino acid sequence of SEQ ID NO: 800; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 600, a HC CDR2 amino acid sequence of SEQ ID NO: 640, and a HC CDR3 amino acid sequence of SEQ ID NO: 680

(xviii) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 721, a LC CDR2 amino acid sequence of SEQ ID NO: 761, and a LC CDR3 amino acid sequence of SEQ ID NO: 801; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 601, a HC CDR2 amino acid sequence of SEQ ID NO: 641, and a HC CDR3 amino acid sequence of SEQ ID NO: 681

(xix) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 722, a LC CDR2 amino acid sequence of SEQ ID NO: 762, and a LC CDR3 amino acid sequence of SEQ ID NO: 802; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 602, a HC CDR2 amino acid sequence of SEQ ID NO: 642, and a HC CDR3 amino acid sequence of SEQ ID NO: 682

(xx) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 723, a LC CDR2 amino acid sequence of SEQ ID NO: 763, and a LC CDR3 amino acid sequence of SEQ ID NO: 803; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 603, a HC CDR2 amino acid sequence of SEQ ID NO: 643, and a HC CDR3 amino acid sequence of SEQ ID NO: 683

(xxi) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 724, a LC CDR2 amino acid sequence of SEQ ID NO: 764, and a LC CDR3 amino acid sequence of SEQ ID NO: 804; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 604, a HC CDR2 amino acid sequence of SEQ ID NO: 644, and a HC CDR3 amino acid sequence of SEQ ID NO: 684

(xxii) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 725, a LC CDR2 amino acid sequence of SEQ ID NO: 765, and a LC CDR3 amino acid sequence of SEQ ID NO: 805; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 605, a HC CDR2 amino acid sequence of SEQ ID NO: 645, and a HC CDR3 amino acid sequence of SEQ ID NO: 685 or

(xxiii) (a) a LC CDR1 amino acid sequence of SEQ ID NO: 726, a LC CDR2 amino acid sequence of SEQ ID NO: 766, and a LC CDR3 amino acid sequence of SEQ ID NO: 806; and

(b) a HC CDR1 amino acid sequence of SEQ ID NO: 606, a HC CDR2 amino acid sequence of SEQ ID NO: 646, and a HC CDR3 amino acid sequence of SEQ ID NO: 686.

In one embodiment, the BCMA binding domain comprises a light chain variable region described herein (e.g., in Table 8 or 9) and/or a heavy chain variable region described herein (e.g., in Table 8 or 9). In one embodiment, the BCMA binding domain is a scFv comprising a light chain and a heavy chain of an amino acid sequence listed in Table 8 or 9. In an embodiment, the BCMA binding domain (e.g., an scFv) comprises: a light chain variable region comprising an amino acid sequence having at least one, two or three modifications (e.g., substitutions, e.g., conservative substitutions) but not more than 30, 20 or 10 modifications (e.g., substitutions, e.g., conservative substitutions) of an amino acid sequence of a light chain variable region provided in Table 8 or 9, or a sequence with 95-99% identity with an amino acid sequence provided in Table 8 or 9; and/or a heavy chain variable region comprising an amino acid sequence having at least one, two or three modifications (e.g., substitutions, e.g., conservative substitutions) but not more than 30, 20 or 10 modifications (e.g., substitutions, e.g., conservative substitutions) of an amino acid sequence of a heavy chain variable region provided in Table 8 or 9, or a sequence with 95-99% identity to an amino acid sequence provided in Table 8 or 9.

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In one embodiment, the BCMA binding domain comprises an amino acid sequence selected from a group consisting of SEQ ID NO: 249; SEQ ID NO: 239, SEQ ID NO: 240; SEQ ID NO: 241; SEQ ID NO: 242; SEQ ID NO: 243; SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 247, SEQ ID NO: 248, SEQ ID NO: 250, SEQ ID NO: 251, SEQ ID NO: 252, SEQ ID NO: 253, SEQ ID NO: 329, SEQ ID NO: 330, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334, SEQ ID NO: 335, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340, SEQ ID NO: 341, SEQ ID NO: 342, SEQ ID NO: 343, SEQ ID NO: 344, SEQ ID NO: 345, SEQ ID NO: 346, SEQ ID NO: 347, SEQ ID NO: 348, SEQ ID NO: 349, SEQ ID NO: 463, SEQ ID NO: 464, SEQ ID NO: 465 and SEQ ID NO: 466; or an amino acid sequence having at least one, two or three modifications (e.g., substitutions, e.g., conservative substitutions) but not more than 30, 20 or 10 modifications (e.g., substitutions, e.g., conservative substitutions) to any of the aforesaid sequences; or a sequence with 95-99% identity to any of the aforesaid sequences. In one embodiment, the BCMA binding domain is a scFv, and a light chain variable region comprising an amino acid sequence described herein, e.g., in Table 8 or 9, is attached to a heavy chain variable region comprising an amino acid sequence described herein, e.g., in Table 8 or 9, via a linker, e.g., a linker described herein. In one embodiment, the BCMA binding domain includes a (Gly4-Ser)n linker, wherein n is 1, 2, 3, 4, 5, or 6 (SEQ ID NO: 10561), preferably 3 (SEQ ID NO: 35). The light chain variable region and heavy chain variable region of a scFv can be, e.g., in any of the following orientations: light chain variable region-linker-heavy chain variable region or heavy chain variable region-linker-light chain variable region.

Any known BCMA CAR, e.g., the BCMA antigen binding domain of any known BCMA CAR, in the art can be used in accordance with the instant disclosure. For example, those described herein.

Exemplary CAR Molecules

In one aspect, a CAR, e.g., a CAR expressed by a cell disclosed herein, comprises a CAR molecule comprising an antigen binding domain that binds to a B cell antigen, e.g., as described herein, such as CD19 or BCMA.

In one embodiment, the CAR comprises a CAR molecule comprising a CD19 antigen binding domain (e.g., a murine, human or humanized antibody or antibody fragment that specifically binds to CD19), a transmembrane domain, and an intracellular signaling domain (e.g., an intracellular signaling domain comprising a costimulatory domain and/or a primary signaling domain).

Exemplary CAR molecules described herein are provided in Table 12. The CAR molecules in Table 12 comprise a CD19 antigen binding domain, e.g., an amino acid sequence of any CD19 antigen binding domain provided in Table 4. Any of the exemplary CAR molecules listed below, or combinations thereof, can be used with the cells and methods disclosed herein.

In one embodiment, the CAR molecule comprises (or consists of) an amino acid sequence as provided in Table 12, or in Table 3 of International Publication No. WO2014/153270, filed Mar. 15, 2014; incorporated herein by reference. In one embodiment, the CAR molecule comprises (or consists of) an amino acid sequence of SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, or SEQ ID NO: 197; or an amino acid sequence having at least one, two, three, four, five, 10, 15, 20 or 30 modifications (e.g., substitutions, e.g., conservative substitutions) but not more than 60, 50, or 40 modifications (e.g., substitutions, e.g., conservative substitutions) of an amino acid sequence of SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, or SEQ ID NO: 197; or an amino acid sequence having 85%, 90%, 95%, 96%, 97%, 98%, 99% identity to an amino acid sequence of SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, or SEQ ID NO: 197.

In one aspect, a CAR, e.g., a CAR expressed by a cell disclosed herein, comprises a CAR molecule comprising an antigen binding domain that binds to BCMA, e.g., comprises a BCMA antigen binding domain (e.g., a murine, human or humanized antibody or antibody fragment that specifically binds to BCMA, e.g., human BCMA), a transmembrane domain, and an intracellular signaling domain (e.g., an intracellular signaling domain comprising a costimulatory domain and/or a primary signaling domain).

Exemplary CAR molecules are provided in Table 13, or Table 1 of WO2016/014565, or as otherwise described herein. The CAR molecules in Table 13 comprise a BCMA antigen binding domain, e.g., an amino acid sequence of any BCMA antigen binding domain provided in Table 8 or 9. of the exemplary CAR molecules listed below, or combinations thereof, can be used with the cells and methods disclosed herein.

In one embodiment, the CAR molecule comprises (or consists of) an amino acid sequence provided in Table 13, or Table 1 of WO2016/014565, or as otherwise described herein. In one embodiment, the CAR molecule comprises (or consists of) an amino acid sequence of SEQ ID NO: 849, SEQ ID NO: 850, SEQ ID NO: 851, SEQ ID NO: 852, SEQ ID NO: 853, SEQ ID NO: 854, SEQ ID NO: 855, SEQ ID NO: 856, SEQ ID NO: 857, SEQ ID NO: 858, SEQ ID NO: 859, SEQ ID NO: 860, SEQ ID NO: 861, SEQ ID NO: 862, SEQ ID NO: 863, SEQ ID NO: 879, SEQ ID NO: 880, SEQ ID NO: 881, SEQ ID NO: 882, SEQ ID NO: 883, SEQ ID NO: 884, SEQ ID NO: 885, SEQ ID NO: 886, SEQ ID NO: 887, SEQ ID NO: 888, SEQ ID NO: 889, SEQ ID NO: 890, SEQ ID NO: 891, SEQ ID NO: 892, SEQ ID NO: 893, SEQ ID NO: 894, SEQ ID NO: 895, SEQ ID NO: 896, SEQ ID NO: 897, SEQ ID NO: 898, or SEQ ID NO: 899; or an amino acid sequence having at least one, two, three, four, five, 10, 15, 20 or 30 modifications (e.g., substitutions, e.g., conservative substitutions) but not more than 60, 50, or 40 modifications (e.g., substitutions, e.g., conservative substitutions) of an amino acid sequence of SEQ ID NO: 849, SEQ ID NO: 850, SEQ ID NO: 851, SEQ ID NO: 852, SEQ ID NO: 853, SEQ ID NO: 854, SEQ ID NO: 855, SEQ ID NO: 856, SEQ ID NO: 857, SEQ ID NO: 858, SEQ ID NO: 859, SEQ ID NO: 860, SEQ ID NO: 861, SEQ ID NO: 862, SEQ ID NO: 863, SEQ ID NO: 879, SEQ ID NO: 880, SEQ ID NO: 881, SEQ ID NO: 882, SEQ ID NO: 883, SEQ ID NO: 884, SEQ ID NO: 885, SEQ ID NO: 886, SEQ ID NO: 887, SEQ ID NO: 888, SEQ ID NO: 889, SEQ ID NO: 890, SEQ ID NO: 891, SEQ ID NO: 892, SEQ ID NO: 893, SEQ ID NO: 894, SEQ ID NO: 895, SEQ ID NO: 896, SEQ ID NO: 897, SEQ ID NO: 898, or SEQ ID NO: 899; or an amino acid sequence having 85%, 90%, 95%, 96%, 97%, 98%, 99% identity to an amino acid sequence of SEQ ID NO: 849, SEQ ID NO: 850, SEQ ID NO: 851, SEQ ID NO: 852, SEQ ID NO: 853, SEQ ID NO: 854, SEQ ID NO: 855, SEQ ID NO: 856, SEQ ID NO: 857, SEQ ID NO: 858, SEQ ID NO: 859, SEQ ID NO: 860, SEQ ID NO: 861, SEQ ID NO: 862, SEQ ID NO: 863, SEQ ID NO: 879, SEQ ID NO: 880, SEQ ID NO: 881, SEQ ID NO: 882, SEQ ID NO: 883, SEQ ID NO: 884, SEQ ID NO: 885, SEQ ID NO: 886, SEQ ID NO: 887, SEQ ID NO: 888, SEQ ID NO: 889, SEQ ID NO: 890, SEQ ID NO: 891, SEQ ID NO: 892, SEQ ID NO: 893, SEQ ID NO: 894, SEQ ID NO: 895, SEQ ID NO: 896, SEQ ID NO: 897, SEQ ID NO: 898, or SEQ ID NO: 899.

›VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGK · 9 of 9

Transmembrane Domains

With respect to the transmembrane domain, in various embodiments, a CAR can be designed to comprise a transmembrane domain that is attached to the extracellular domain of the CAR, e.g., attached to any of the antigen binding domains listed above. The transmembrane domain can also, in some embodiments, be attached to an intracellular domain of the CAR (e.g., a costimulatory and/or primary signalling domain). A transmembrane domain can include one or more additional amino acids adjacent to the transmembrane region, e.g., one or more amino acid associated with the extracellular region of the protein from which the transmembrane was derived (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 up to 15 amino acids of the extracellular region) and/or one or more additional amino acids associated with the intracellular region of the protein from which the transmembrane protein is derived (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 up to 15 amino acids of the intracellular region). In one aspect, the transmembrane domain is one that is associated with one of the other domains of the CAR e.g., in one embodiment, the transmembrane domain may be from the same protein that the signaling domain, costimulatory domain or the hinge domain is derived from. In another aspect, the transmembrane domain is not derived from the same protein that any other domain of the CAR is derived from. In some instances, the transmembrane domain can be selected or modified by amino acid substitution to avoid binding of such domains to the transmembrane domains of the same or different surface membrane proteins, e.g., to minimize interactions with other members of the receptor complex. In one aspect, the transmembrane domain is capable of homodimerization with another CAR on the cell surface of a CAR-expressing cell. In a different aspect, the amino acid sequence of the transmembrane domain may be modified or substituted so as to minimize interactions with the binding domains of the native binding partner present in the same CAR-expressing cell.

The transmembrane domain may be derived either from a natural or from a recombinant source. Where the source is natural, the domain may be derived from any membrane-bound or transmembrane protein. In one aspect the transmembrane domain is capable of signaling to the intracellular domain(s) whenever the CAR has bound to a target. A transmembrane domain of particular use in this disclosure may include at least the transmembrane region(s) of e.g., the alpha, beta or zeta chain of the T-cell receptor, CD28, CD27, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154. In some embodiments, a transmembrane domain may include at least the transmembrane region(s) of, e.g., KIRDS2, OX40, CD2, CD27, LFA-1 (CD11a, CD18), ICOS (CD278), 4-1BB (CD137), GITR, CD40, BAFFR, HVEM (LIGHTR), SLAMF7, NKp80 (KLRF1), NKp44, NKp30, NKp46, CD160, CD19, IL2R beta, IL2R gamma, IL7R α, ITGA1, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CD11 d, ITGAE, CD103, ITGAL, CD11a, LFA-1, ITGAM, CD11b, ITGAX, CD11c, ITGB1, CD29, ITGB2, CD18, LFA-1, ITGB7, TNFR2, DNAM1 (CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (Tactile), CEACAM1, CRTAM, Ly9 (CD229), CD160 (BY55), PSGL1, CD100 (SEMA4D), SLAMF6 (NTB-A, Lyl08), SLAM (SLAMF1, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, PAG/Cbp, NKG2D, NKG2C, or atransmembrane domain derived from any protein thereof.

In some instances, the transmembrane domain can be attached to the extracellular region of the CAR, e.g., the antigen binding domain of the CAR, via a hinge, e.g., a hinge from a human protein. For example, in one embodiment, the hinge can be a human Ig (immunoglobulin) hinge (e.g., an IgG4 hinge, an IgD hinge), a GS linker (e.g., a GS linker described herein), a KIR2DS2 hinge or a CD8a hinge. In one embodiment, the hinge or spacer comprises (or consists of) the amino acid sequence of SEQ ID NO: 5. In one aspect, the transmembrane domain comprises (or consists of) a transmembrane domain of SEQ ID NO: 13.

In certain embodiments, the encoded transmembrane domain comprises an amino acid sequence of a CD8 transmembrane domain having at least one, two or three modifications but not more than 20, 10 or 5 modifications of an amino acid sequence of SEQ ID NO: 13, or a sequence with 95-99% identity to an amino acid sequence of SEQ ID NO: 13. In one embodiment, the encoded transmembrane domain comprises the sequence of SEQ ID NO: 13.

In other embodiments, the nucleic acid molecule encoding the CAR comprises a nucleotide sequence of a CD8 transmembrane domain, e.g., comprising the sequence of SEQ ID NO: 14, or a sequence with 95-99% identity thereof.

In certain embodiments, the encoded antigen binding domain is connected to the transmembrane domain by a hinge region. In one embodiment, the encoded hinge region comprises the amino acid sequence of a CD8 hinge, e.g., SEQ ID NO: 5; or the amino acid sequence of an IgG4 hinge, e.g., SEQ ID NO: 7, or a sequence with 95-99% identity to SEQ ID NO: 5 or 7. In other embodiments, the nucleic acid sequence encoding the hinge region comprises a sequence of SEQ ID NO: 6 or SEQ ID NO: 8, corresponding to a CD8 hinge or an IgG4 hinge, respectively, or a sequence with 95-99% identity to SEQ ID NO:6 or 8.

In one aspect, the hinge or spacer comprises an IgG4 hinge. For example, in one embodiment, the hinge or spacer comprises a hinge of the amino acid sequence

(SEQ ID NO: 7) ESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQE DPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYK CKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNV FSCSVMHEALHNHYTQKSLSLSLGKM.

In some embodiments, the hinge or spacer comprises a hinge encoded by a nucleotide sequence of

(SEQ ID NO: 8)

GAGAGCAAGTACGGCCCTCCCTGCCCCCCTTGCCCTGCCCCCGAGTTCCTG
GGCGGACCCAGCGTGTTCCTGTTCCCCCCCAAGCCCAAGGACACCCTGATG
ATCAGCCGGACCCCCGAGGTGACCTGTGTGGTGGTGGACGTGTCCCAGGAG
GACCCCGAGGTCCAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAAC
GCCAAGACCAAGCCCCGGGAGGAGCAGTTCAATAGCACCTACCGGGTGGTG
TCCGTGCTGACCGTGCTGCACCAGGACTGGCTGAACGGCAAGGAATACAAG
TGTAAGGTGTCCAACAAGGGCCTGCCCAGCAGCATCGAGAAAACCATCAGC
AAGGCCAAGGGCCAGCCTCGGGAGCCCCAGGTGTACACCCTGCCCCCTAGC
CAAGAGGAGATGACCAAGAACCAGGTGTCCCTGACCTGCCTGGTGAAGGGC
TTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCCGAG
AACAACTACAAGACCACCCCCCCTGTGCTGGACAGCGACGGCAGCTTCTTC
CTGTACAGCCGGCTGACCGTGGACAAGAGCCGGTGGCAGGAGGGCAACGTC
›TTTAGCTGCTCCGTGATGCACGAGGCCCTGCACAACCACTACACCCAGAAG

AGCCTGAGCCTGTCCCTGGGCAAGATG.

In one aspect, the hinge or spacer comprises an IgD hinge. For example, in one embodiment, the hinge or spacer comprises a hinge of the amino acid sequence

(SEQ ID NO: 9) RWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNTGRGGEEKKKEKEKE EQEERETKTPECPSHTQPLGVYLLTPAVQDLWLRDKATFTCFVVGSDLKDA HLTWEVAGKVPTGGVEEGLLERHSNGSQSQHSRLTLPRSLWNAGTSVTCTL NHPSLPPQRLMALREPAAQAPVKLSLNLLASSDPPEAASWLLCEVSGESPP NILLMWLEDQREVNTSGEAPARPPPQPGSTTFWAWSVLRVPAPPSPQPATY TCVVSHEDSRTLLNASRSLEVSYVTDH.

In some embodiments, the hinge or spacer comprises a hinge encoded by a nucleotide sequence of

(SEQ ID NO: 10)

AGGTGGCCCGAAAGTCCCAAGGCCCAGGCATCTAGTGTTCCTACTGCACAG
CCCCAGGCAGAAGGCAGCCTAGCCAAAGCTACTACTGCACCTGCCACTACG
CGCAATACTGGCCGTGGCGGGGAGGAGAAGAAAAAGGAGAAAGAGAAAGAA
GAACAGGAAGAGAGGGAGACCAAGACCCCTGAATGTCCATCCCATACCCAG
CCGCTGGGCGTCTATCTCTTGACTCCCGCAGTACAGGACTTGTGGCTTAGA
GATAAGGCCACCTTTACATGTTTCGTCGTGGGCTCTGACCTGAAGGATGCC
CATTTGACTTGGGAGGTTGCCGGAAAGGTACCCACAGGGGGGGTTGAGGAA
GGGTTGCTGGAGCGCCATTCCAATGGCTCTCAGAGCCAGCACTCAAGACTC
ACCCTTCCGAGATCCCTGTGGAACGCCGGGACCTCTGTCACATGTACTCTA
AATCATCCTAGCCTGCCCCCACAGCGTCTGATGGCCCTTAGAGAGCCAGCC
GCCCAGGCACCAGTTAAGCTTAGCCTGAATCTGCTCGCCAGTAGTGATCCC
CCAGAGGCCGCCAGCTGGCTCTTATGCGAAGTGTCCGGCTTTAGCCCGCCC
AACATCTTGCTCATGTGGCTGGAGGACCAGCGAGAAGTGAACACCAGCGGC
TTCGCTCCAGCCCGGCCCCCACCCCAGCCGGGTTCTACCACATTCTGGGCC
TGGAGTGTCTTAAGGGTCCCAGCACCACCTAGCCCCCAGCCAGCCACATAC
›ACCTGTGTTGTGTCCCATGAAGATAGCAGGACCCTGCTAAATGCTTCTAGG · 1 of 15

AGTCTGGAGGTTTCCTACGTGACTGACCATT.

In one aspect, the transmembrane domain may be recombinant, in which case it will comprise predominantly hydrophobic residues such as leucine and valine. In one aspect a triplet of phenylalanine, tryptophan and valine can be found at each end of a recombinant transmembrane domain.

Optionally, a short oligo- or polypeptide linker, between 2 and 10 amino acids in length may form the linkage between the transmembrane domain and the cytoplasmic region of the CAR. A glycine-serine doublet provides a particularly suitable linker. For example, in one aspect, the linker comprises the amino acid sequence of GGGGSGGGGS (SEQ ID NO:11). In some embodiments, the linker is encoded by a nucleotide sequence of GGTGGCGGAGGTTCTGGAGGTGGAGGTTCC (SEQ ID NO: 12).

In one aspect, the hinge or spacer comprises a KIR2DS2 hinge.

Signaling Domains

In embodiments having an intracellular signaling domain, such a domain can contain, e.g., one or more of a primary signaling domain and/or a costimulatory signaling domain. In some embodiments, the intracellular signaling domain comprises a sequence encoding a primary signaling domain. In some embodiments, the intracellular signaling domain comprises a costimulatory signaling domain. In some embodiments, the intracellular signaling domain comprises a primary signaling domain and a costimulatory signaling domain.

The intracellular signaling sequences within the cytoplasmic portion of the CAR may be linked to each other in a random or specified order. Optionally, a short oligo- or polypeptide linker, for example, between 2 and 10 amino acids (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids) in length may form the linkage between intracellular signaling sequences. In one embodiment, a glycine-serine doublet can be used as a suitable linker. In one embodiment, a single amino acid, e.g., an alanine, a glycine, can be used as a suitable linker.

In one aspect, the intracellular signaling domain is designed to comprise two or more, e.g., 2, 3, 4, 5, or more, costimulatory signaling domains. In an embodiment, the two or more, e.g., 2, 3, 4, 5, or more, costimulatory signaling domains, are separated by a linker molecule, e.g., a linker molecule described herein. In one embodiment, the intracellular signaling domain comprises two costimulatory signaling domains. In some embodiments, the linker molecule is a glycine residue. In some embodiments, the linker is an alanine residue.

Primary Signaling Domains

A primary signaling domain regulates primary activation of the TCR complex either in a stimulatory way, or in an inhibitory way. Primary intracellular signaling domains that act in a stimulatory manner may contain signaling motifs which are known as immunoreceptor tyrosine-based activation motifs or ITAMs.

Examples of ITAM containing primary intracellular signaling domains that are of particular use in the disclosure include those of CD3 zeta, common FcR gamma (FCER1G), Fc gamma RIIa, FcR beta (Fc Epsilon R1b), CD3 gamma, CD3 delta, CD3 epsilon, CD79a, CD79b, DAP10, and DAP12. In one embodiment, a CAR of the disclosure comprises an intracellular signaling domain, e.g., a primary signaling domain of CD3-zeta.

In one embodiment, the encoded primary signaling domain comprises a functional signaling domain of CD3 zeta. The encoded CD3 zeta primary signaling domain can comprise an amino acid sequence having at least one, two or three modifications but not more than 20, 10 or 5 modifications of an amino acid sequence of SEQ ID NO: 21 or SEQ ID NO: 24, or a sequence with 95-99% identity to an amino acid sequence of SEQ ID NO: 21 or SEQ ID NO: 24. In some embodiments, the encoded primary signaling domain comprises a sequence of SEQ ID NO: 21 or SEQ ID NO: 24. In other embodiments, the nucleic acid sequence encoding the primary signaling domain comprises a sequence of SEQ ID NO: 22 or SEQ ID NO: 25, or a sequence with 95-99% identity thereof.

Costimulatory Signaling Domains

In some embodiments, the encoded intracellular signaling domain comprises a costimulatory signaling domain. For example, the intracellular signaling domain can comprise a primary signaling domain and a costimulatory signaling domain. In some embodiments, the encoded costimulatory signaling domain comprises a functional signaling domain of a protein chosen from one or more of CD27, CD28, 4-1BB (CD137), OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, a ligand that specifically binds with CD83, CDS, ICAM-1, GITR, BAFFR, HVEM (LIGHTR), SLAMF7, NKp80 (KLRF1), CD160, CD19, CD4, CD8alpha, CD8beta, IL2R beta, IL2R gamma, IL7R alpha, ITGA4, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CD11d, ITGAE, CD103, ITGAL, CD11a, LFA-1, ITGAM, CD1 b, ITGAX, CD11c, ITGB1, CD29, ITGB2, CD18, LFA-1, ITGB7, TNFR2, TRANCE/RANKL, DNAM1 (CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (Tactile), CEACAM1, CRTAM, Ly9 (CD229), CD160 (BY55), PSGL1, CD100 (SEMA4D), CD69, SLAMF6 (NTB-A, Lyl08), SLAM (SLAMF1, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, LAT, GADS, SLP-76, PAG/Cbp, NKp44, NKp30, NKp46, or NKG2D.

In certain embodiments, the encoded costimulatory signaling domain comprises an amino acid sequence having at least one, two or three modifications but not more than 20, 10 or 5 modifications of an amino acid sequence of SEQ ID NO: 16 or SEQ ID NO: 19, or a sequence with 95-99% identity to an amino acid sequence of SEQ ID NO: 16 or SEQ ID NO: 19. In one embodiment, the encoded costimulatory signaling domain comprises a sequence of SEQ ID NO: 16 or SEQ ID NO: 19. In other embodiments, the nucleic acid sequence encoding the costimulatory signaling domain comprises a sequence of SEQ ID NO: 17 or SEQ ID NO: 20, or a sequence with 95-99% identity thereof.

In other embodiments, the encoded intracellular domain comprises the sequence of SEQ ID NO: 16 or SEQ ID NO: 19, and the sequence of SEQ ID NO: 21 or SEQ ID NO: 24, wherein the sequences comprising the intracellular signaling domain are expressed in the same frame and as a single polypeptide chain.

›ACCTGTGTTGTGTCCCATGAAGATAGCAGGACCCTGCTAAATGCTTCTAGG · 2 of 15

In certain embodiments, the nucleic acid sequence encoding the intracellular signaling domain comprises a sequence of SEQ ID NO: 17 or SEQ ID NO: 20, or a sequence with 95-99% identity thereof, and a sequence of SEQ ID NO: 22 or SEQ ID NO: 25, or a sequence with 95-99% identity thereof.

In some embodiments, the nucleic acid molecule further encodes a leader sequence. In one embodiment, the leader sequence comprises the sequence of SEQ ID NO: 2.

In one aspect, the intracellular signaling domain is designed to comprise the signaling domain of CD3-zeta and the signaling domain of CD28. In one aspect, the intracellular signaling domain is designed to comprise the signaling domain of CD3-zeta and the signaling domain of 4-1BB. In one aspect, the signaling domain of 4-1BB is a signaling domain of SEQ ID NO: 16. In one aspect, the signaling domain of CD3-zeta is a signaling domain of SEQ ID NO: 21.

In one aspect, the intracellular signaling domain is designed to comprise the signaling domain of CD3-zeta and the signaling domain of CD27. In one aspect, the signaling domain of CD27 comprises an amino acid sequence of QRRKYRSNKGESPVEPAEPCRYSCPREEEGSTIPIQEDYRKPEPACSP (SEQ ID NO: 19). In one aspect, the signalling domain of CD27 is encoded by a nucleic acid sequence of AGGAGTAAGAGGAGCAGGCTCCTGCACAGTGACTACATGAACATGACTCCCCGCC GCCCCGGGCCCACCCGCAAGCATTACCAGCCCTATGCCCCACCACGCGACTTCGC AGCCTATCGCTCC (SEQ ID NO: 20).

Vectors

In another aspect, the disclosure pertains to a vector comprising a nucleic acid sequence encoding a CAR described herein. In one embodiment, the vector is chosen from a DNA vector, an RNA vector, a plasmid, a lentivirus vector, adenoviral vector, or a retrovirus vector. In one embodiment, the vector is a lentivirus vector. These vectors or portions thereof may, among other things, be used to create template nucleic acids, as described herein for use with the CRISPR systems as described herein. Alternatively, the vectors may be used to deliver nucleic acid directly to the cell, e.g., the immune effector cell, e.g., the T cell, e.g., the allogeneic T cell, independent of the CRISPR system.

The present disclosure also provides vectors in which a DNA disclosed herein is inserted. Vectors derived from retroviruses such as the lentivirus are suitable tools to achieve long-term gene transfer since they allow long-term, stable integration of a transgene and its propagation in daughter cells. Lentiviral vectors have the added advantage over vectors derived from onco-retroviruses such as murine leukemia viruses in that they can transduce non-proliferating cells, such as hepatocytes. They also have the added advantage of low immunogenicity. A retroviral vector may also be, e.g., a gammaretroviral vector. A gammaretroviral vector may include, e.g., a promoter, a packaging signal (ψ), a primer binding site (PBS), one or more (e.g., two) long terminal repeats (LTR), and a transgene of interest, e.g., a gene encoding a CAR. A gammaretroviral vector may lack viral structural gens such as gag, pol, and env. Exemplary gammaretroviral vectors include Murine Leukemia Virus (MLV), Spleen-Focus Forming Virus (SFFV), and Myeloproliferative Sarcoma Virus (MPSV), and vectors derived therefrom. Other gammaretroviral vectors are described, e.g., in Tobias Maetzig et al., “Gammaretroviral Vectors: Biology, Technology and Application” Viruses. 2011 June; 3(6): 677-713.

In another embodiment, the vector comprising the nucleic acid encoding the desired CAR of the disclosure is an adenoviral vector (A5/35). In another embodiment, the expression of nucleic acids encoding CARs can be accomplished using of transposons such as sleeping beauty, crisper, CAS9, and zinc finger nucleases. See below June et al. 2009 Nature Reviews Immunology 9.10: 704-716, is incorporated herein by reference.

The nucleic acid can be cloned into a number of types of vectors. For example, the nucleic acid can be cloned into a vector including, but not limited to a plasmid, a phagemid, a phage derivative, an animal virus, and a cosmid. Vectors of particular interest include expression vectors, replication vectors, probe generation vectors, and sequencing vectors.

Disclosed herein are methods for producing an in vitro transcribed RNA CAR. The present disclosure also includes a CAR encoding RNA construct that can be directly transfected into a cell. A method for generating mRNA for use in transfection can involve in vitro transcription (IVT) of a template with specially designed primers, followed by polyA addition, to produce a construct containing 3′ and 5′ untranslated sequence (“UTR”), a 5′ cap and/or Internal Ribosome Entry Site (IRES), the nucleic acid to be expressed, and a polyA tail, typically 50-2000 bases in length (SEQ ID NO: 10555). RNA so produced can efficiently transfect different kinds of cells. In one aspect, the template includes sequences for the CAR.

Non-Viral Delivery Methods

In some aspects, non-viral methods can be used to deliver a nucleic acid encoding a CAR described herein into a cell or tissue or a subject.

In some embodiments, the non-viral method includes the use of a transposon (also called a transposable element). In some embodiments, a transposon is a piece of DNA that can insert itself at a location in a genome, for example, a piece of DNA that is capable of self-replicating and inserting its copy into a genome, or a piece of DNA that can be spliced out of a longer nucleic acid and inserted into another place in a genome. For example, a transposon comprises a DNA sequence made up of inverted repeats flanking genes for transposition.

In some embodiments, cells, e.g., T or NK cells, are generated that express a CAR described herein by using a combination of gene insertion using the SBTS and genetic editing using a nuclease (e.g., Zinc finger nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), the CRISPR/Cas system, or engineered meganuclease re-engineered homing endonucleases). In specific embodiments, the use of the gene editing system inserts the nucleic acid sequence encoding the CAR at a defined locus, e.g., within a TET2 intron, e.g., within a sequence listed in Table 3.

›ACCTGTGTTGTGTCCCATGAAGATAGCAGGACCCTGCTAAATGCTTCTAGG · 3 of 15

In some embodiments, modified cells as disclosed herein, e.g., T or NK cells, e.g., autologous or allogeneic T cells, e.g., described herein, (e.g., that express a CAR described herein) are generated by contacting the cells with (a) a composition comprising one or more gRNA molecules, e.g., as described herein, and one or more Cas molecules, e.g., a Cas9 molecule, e.g., as described herein, and (b) nucleic acid comprising sequence encoding a CAR, e.g., described herein (such as a template nucleic acid molecule as described herein). Without being bound by theory, said composition of (a), above, will induce a break at or near the genomic DNA targeted by the targeting domain of the gRNA molecule(s), and the nucleic acid of (b) will incorporate, e.g., partially or wholly, into the genome at or near said break, such that upon integration, the encoded CAR molecule is expressed. In some embodiments, the % incorporation of the nucleic acid sequence is at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65% or 70% at a time point after the cell is contacted, as measured by a suitable method, e.g., PCR, sequencing, single-cell genotyping, ddPCR genotyping, Southern blot, and/or cell surface staining. In some embodiments, a population of cells is provided, for example, after subsequent selection steps, wherein the nucleic acid sequence is incorporated in, e.g., at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% of the cells of the population.

In embodiments, expression of the CAR will be controlled by promoters or other regulatory elements endogenous to the genome (e.g., the promoter controlling expression from the gene in which the nucleic acid of (b) was inserted). In other embodiments, the nucleic acid of (b) further comprises a promoter and/or other regulatory elements, e.g., as described herein, e.g., an EF1-alpha promoter, operably linked to the sequence encoding the CAR, such that upon integration, expression of the CAR is controlled by that promoter and/or other regulatory elements. Additional features of the disclosure relating to use of CRISPR/Cas9 systems, e.g., as described herein, to direct incorporation of nucleic acid sequence encoding a CAR, e.g., as described herein, are described elsewhere in this application, e.g., in the section relating to gene insertion and homologous recombination. In embodiments, the composition of a) above is a composition comprising RNPs comprising the one or more gRNA molecules. In embodiments, RNPs comprising gRNAs targeting unique target sequences are introduced into the cell simultaneously, e.g., as a mixture of RNPs comprising the one or more gRNAs. In embodiments, RNPs comprising gRNAs targeting unique target sequences are introduced into the cell sequentially.

In some embodiments, the modified cells are generated by contacting a cell with (a) a composition comprising one or more gRNA molecules, e.g., as described herein, and one or more Cas molecules, e.g., a Cas9 molecule, e.g., as described herein, and (b) a nucleic acid that is capable of disrupting the expression of TET2. Without being bound by theory, said composition of (a), above, will induce a break at or near the genomic DNA targeted by the targeting domain of the gRNA molecule(s), and the nucleic acid of (b) will incorporate, e.g., partially or wholly, into the genome at or near said break, such that upon integration, the expression of at least one TET2 isoform is reduced.

In some embodiments, the modified cells are generated by contacting a cell with (a) a composition comprising one or more gRNA molecules, e.g., as described herein, and one or more Cas molecules, e.g., a Cas9 molecule, e.g., as described herein, and (b) a nucleic acid comprising a sequence encoding a CAR. Without being bound by theory, said composition of (a), above, will induce a break at or near the genomic DNA targeted by the targeting domain of the gRNA molecule(s), and nucleic acid comprising a sequence encoding a CAR of (b) will incorporate, e.g., partially or wholly, into the genome at or near said break, such that upon integration, the expression of at least one TET2 isoform is reduced.

In some embodiments, use of a non-viral method of delivery permits reprogramming of cells, e.g., T or NK cells, and direct infusion of the cells into a subject. Advantages of non-viral vectors include but are not limited to the ease and relatively low cost of producing sufficient amounts required to meet a patient population, stability during storage, and lack of immunogenicity.

Inhibitory Domains

In an embodiment, the vector comprises a nucleic acid sequence that encodes a CAR, e.g., a CAR described herein, and a nucleic acid sequence that encodes an inhibitory molecule comprising: an inhKIR cytoplasmic domain; a transmembrane domain, e.g., a KIR transmembrane domain; and an inhibitor cytoplasmic domain, e.g., an ITIM domain, e.g., an inhKIR ITIM domain. In an embodiment the inhibitory molecule is a naturally occurring inhKIR, or a sequence sharing at least 50, 60, 70, 80, 85, 90, 95, or 99% homology with, or that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, or 20 residues from, a naturally occurring inhKIR.

In an embodiment, the nucleic acid sequence that encodes an inhibitory molecule comprises: a SLAM family cytoplasmic domain; a transmembrane domain, e.g., a SLAM family transmembrane domain; and an inhibitor cytoplasmic domain, e.g., a SLAM family domain, e.g., an SLAM family ITIM domain. In an embodiment the inhibitory molecule is a naturally occurring SLAM family member, or a sequence sharing at least 50, 60, 70, 80, 85, 90, 95, or 99% homology with, or that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, or 20 residues from, a naturally occurring SLAM family member.

In one embodiment, the vector is an in vitro transcribed vector, e.g., a vector that transcribes RNA of a nucleic acid molecule described herein. In one embodiment, the nucleic acid sequence in the vector further comprises a poly(A) tail, e.g., a poly A tail. In one embodiment, the nucleic acid sequence in the vector further comprises a 3′UTR, e.g., a 3′ UTR described herein, e.g., comprising at least one repeat of a 3′UTR derived from human beta-globulin. In one embodiment, the nucleic acid sequence in the vector further comprises promoter, e.g., a T2A promoter.

›ACCTGTGTTGTGTCCCATGAAGATAGCAGGACCCTGCTAAATGCTTCTAGG · 4 of 15

Promoters

In one embodiment, the vector further comprises a promoter. In some embodiments, the promoter is chosen from an EF-1 promoter, a CMV IE gene promoter, an EF-1a promoter, an ubiquitin C promoter, or a phosphoglycerate kinase (PGK) promoter. In one embodiment, the promoter is an EF-1 promoter. In one embodiment, the EF-1 promoter comprises a sequence of SEQ ID NO: 1.

Host Cells for CAR Expression

As noted above, in some aspects the disclosure pertains to a cell, e.g., an immune effector cell, (e.g., a population of cells, e.g., a population of immune effector cells) comprising a nucleic acid molecule (e.g., a template nucleic acid molecule), a CAR polypeptide molecule, or a vector as described herein.

In certain aspects of the present disclosure, immune effector cells, e.g., T cells, can be obtained from a unit of blood collected from a subject using any number of techniques known to the skilled artisan, such as Ficoll™ separation. In one preferred aspect, cells from the circulating blood of an individual are obtained by apheresis. The apheresis product typically contains lymphocytes, including T cells, monocytes, granulocytes, B cells, other nucleated white blood cells, red blood cells, and platelets. In one aspect, the cells collected by apheresis may be washed to remove the plasma fraction and, optionally, to place the cells in an appropriate buffer or media for subsequent processing steps. In one embodiment, the cells are washed with phosphate buffered saline (PBS). In an alternative embodiment, the wash solution lacks calcium and may lack magnesium or may lack many if not all divalent cations.

Initial activation steps in the absence of calcium can lead to magnified activation. As those of ordinary skill in the art would readily appreciate a washing step may be accomplished by methods known to those in the art, such as by using a semi-automated “flow-through” centrifuge (for example, the Cobe 2991 cell processor, the Baxter CytoMate, or the Haemonetics Cell Saver 5) according to the manufacturer's instructions. After washing, the cells may be resuspended in a variety of biocompatible buffers, such as, for example, Ca-free, Mg-free PBS, PlasmaLyte A, or other saline solution with or without buffer. Alternatively, the undesirable components of the apheresis sample may be removed and the cells directly resuspended in culture media.

It is recognized that the methods of the application can utilize culture media conditions comprising 5% or less, for example 2%, human AB serum, and employ known culture media conditions and compositions, for example those described in Smith et al., “Ex vivo expansion of human T cells for adoptive immunotherapy using the novel Xeno-free CTS Immune Cell Serum Replacement” Clinical & Translational Immunology (2015) 4, e31; doi: 10.1038/cti.2014.31.

In one aspect, T cells are isolated from peripheral blood lymphocytes by lysing the red blood cells and depleting the monocytes, for example, by centrifugation through a PERCOLL™ gradient or by counterflow centrifugal elutriation.

The methods described herein can include, e.g., selection of a specific subpopulation of immune effector cells, e.g., T cells, that are a T regulatory cell-depleted population, CD25+ depleted cells, using, e.g., a negative selection technique, e.g., described herein. Preferably, the population of T regulatory depleted cells contains less than 30%, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1% of CD25+ cells.

In one embodiment, T regulatory cells, e.g., CD25+ T cells, are removed from the population using an anti-CD25 antibody, or fragment thereof, or a CD25-binding ligand, IL-2. In one embodiment, the anti-CD25 antibody, or fragment thereof, or CD25-binding ligand is conjugated to a substrate, e.g., a bead, or is otherwise coated on a substrate, e.g., a bead. In one embodiment, the anti-CD25 antibody, or fragment thereof, is conjugated to a substrate as described herein.

In one embodiment, the T regulatory cells, e.g., CD25+ T cells, are removed from the population using CD25 depletion reagent from Miltenyi™. In one embodiment, the ratio of cells to CD25 depletion reagent is 1e7 cells to 20 uL, or 1e7 cells to 15 uL, or 1e7 cells to 10 uL, or 1e7 cells to 5 uL, or 1e7 cells to 2.5 uL, or 1e7 cells to 1.25 uL. In one embodiment, e.g., for T regulatory cells, e.g., CD25+ depletion, greater than 500 million cells/ml is used. In a further aspect, a concentration of cells of 600, 700, 800, or 900 million cells/ml is used.

In one embodiment, the population of immune effector cells to be depleted includes about 6×10 9 CD25+ T cells. In other aspects, the population of immune effector cells to be depleted include about 1×10 9 to 1×10 10 CD25+ T cell, and any integer value in between. In one embodiment, the resulting population T regulatory depleted cells has 2×10 9 T regulatory cells, e.g., CD25+ cells, or less (e.g., 1×10 9 , 5×10 8 , 1×10 8 , 5×10 7 , 1×10 7 , or less CD25+ cells).

In one embodiment, the T regulatory cells, e.g., CD25+ cells, are removed from the population using the CliniMAC system with a depletion tubing set, such as, e.g., tubing 162-01. In one embodiment, the CliniMAC system is run on a depletion setting such as, e.g., DEPLETION2.1.

Without wishing to be bound by a particular theory, decreasing the level of negative regulators of immune cells (e.g., decreasing the number of unwanted immune cells, e.g., TREG cells), in a subject prior to apheresis or during manufacturing of a CAR-expressing cell product can reduce the risk of subject relapse. For example, methods of depleting TREG cells are known in the art. Methods of decreasing TREG cells include, but are not limited to, cyclophosphamide, anti-GITR antibody (an anti-GITR antibody described herein), CD25-depletion, and combinations thereof.

In some embodiments, the manufacturing methods comprise reducing the number of (e.g., depleting) TREG cells prior to manufacturing of the CAR-expressing cell. For example, manufacturing methods comprise contacting the sample, e.g., the apheresis sample, with an anti-GITR antibody and/or an anti-CD25 antibody (or fragment thereof, or a CD25-binding ligand), e.g., to deplete TREG cells prior to manufacturing of the CAR-expressing cell (e.g., T cell, NK cell) product.

›ACCTGTGTTGTGTCCCATGAAGATAGCAGGACCCTGCTAAATGCTTCTAGG · 5 of 15

In an embodiment, a subject is pre-treated with one or more therapies that reduce TREG cells prior to collecting cells for CAR-expressing cell product manufacturing, thereby reducing the risk of subject relapse to CAR-expressing cell treatment. In an embodiment, methods of decreasing TREG cells include, but are not limited to, administration to the subject of one or more of cyclophosphamide, anti-GITR antibody, CD25-depletion, or a combination thereof. Administration of one or more of cyclophosphamide, anti-GITR antibody, CD25-depletion, or a combination thereof, can occur before, during or after an infusion of the CAR-expressing cell product.

In an embodiment, a subject is pre-treated with cyclophosphamide to reduce TREG cells prior to collecting cells for CAR-expressing cell product manufacturing, thereby reducing the risk of subject relapse to CAR-expressing cell treatment. In an embodiment, a subject is pre-treated with an anti-GITR antibody prior to collection of cells for CAR-expressing cell product manufacturing, thereby reducing the risk of subject relapse to CAR-expressing cell treatment.

In one embodiment, the population of cells to be removed are neither the regulatory T cells or tumor cells, but cells that otherwise negatively affect the expansion and/or function of CART cells, e.g. cells expressing CD14, CD11b, CD33, CD15, or other markers expressed by potentially immune suppressive cells. In one embodiment, such cells are envisioned to be removed concurrently with regulatory T cells and/or tumor cells, or following said depletion, or in another order.

The methods described herein can include more than one selection step, e.g., more than one depletion step. Enrichment of a T cell population by negative selection can be accomplished, e.g., with a combination of antibodies directed to surface markers unique to the negatively selected cells. One method is cell sorting and/or selection via negative magnetic immunoadherence or flow cytometry that uses a cocktail of monoclonal antibodies directed to cell surface markers present on the cells negatively selected. For example, to enrich for CD4+ cells by negative selection, a monoclonal antibody cocktail can include antibodies to CD14, CD20, CD11b, CD16, HLA-DR, and CD8.

The methods described herein can further include removing cells from the population which express a tumor antigen, e.g., a tumor antigen that does not comprise CD25, e.g., CD19, CD30, CD38, CD123, CD20, CD14 or CD11b, to thereby provide a population of T regulatory depleted, e.g., CD25+ depleted, and tumor antigen depleted cells that are suitable for expression of a CAR, e.g., a CAR described herein. In one embodiment, tumor antigen expressing cells are removed simultaneously with the T regulatory, e.g., CD25+ cells. For example, an anti-CD25 antibody, or fragment thereof, and an anti-tumor antigen antibody, or fragment thereof, can be attached to the same substrate, e.g., bead, which can be used to remove the cells or an anti-CD25 antibody, or fragment thereof, or the anti-tumor antigen antibody, or fragment thereof, can be attached to separate beads, a mixture of which can be used to remove the cells. In other embodiments, the removal of T regulatory cells, e.g., CD25+ cells, and the removal of the tumor antigen expressing cells is sequential, and can occur, e.g., in either order.

Also provided are methods that include removing cells from the population which express a check point inhibitor, e.g., a check point inhibitor described herein, e.g., one or more of PD1+ cells, LAG3+ cells, and TIM3+ cells, to thereby provide a population of T regulatory depleted, e.g., CD25+ depleted cells, and check point inhibitor depleted cells, e.g., PD1+, LAG3+ and/or TIM3+ depleted cells. Exemplary check point inhibitors include B7-H1, B7-1, CD160, P1H, 2B4, PD1, TIM3, CEACAM (e.g., CEACAM-1, CEACAM-3 and/or CEACAM-5), LAG3, TIGIT, CTLA-4, BTLA and LAIR1. In one embodiment, check point inhibitor expressing cells are removed simultaneously with the T regulatory, e.g., CD25+ cells. For example, an anti-CD25 antibody, or fragment thereof, and an anti-check point inhibitor antibody, or fragment thereof, can be attached to the same bead which can be used to remove the cells, or an anti-CD25 antibody, or fragment thereof, and the anti-check point inhibitor antibody, or fragment there, can be attached to separate beads, a mixture of which can be used to remove the cells. In other embodiments, the removal of T regulatory cells, e.g., CD25+ cells, and the removal of the check point inhibitor expressing cells is sequential, and can occur, e.g., in either order.

Methods described herein can include a positive selection step. For example, T cells can be isolated by incubation with anti-CD3/anti-CD28 (e.g., 3×28)-conjugated beads, such as DYNABEADS® M-450 CD3/CD28 T, for a time period sufficient for positive selection of the desired T cells. In one embodiment, the time period is about 30 minutes. In a further embodiment, the time period ranges from 30 minutes to 36 hours or longer and all integer values there between. In a further embodiment, the time period is at least 1, 2, 3, 4, 5, or 6 hours. In yet another embodiment, the time period is 10 to 24 hours, e.g., 24 hours. Longer incubation times may be used to isolate T cells in any situation where there are few T cells as compared to other cell types, such in isolating tumor infiltrating lymphocytes (TIL) from tumor tissue or from immunocompromised individuals. Further, use of longer incubation times can increase the efficiency of capture of CD8+ T cells. Thus, by simply shortening or lengthening the time T cells are allowed to bind to the CD3/CD28 beads and/or by increasing or decreasing the ratio of beads to T cells (as described further herein), subpopulations of T cells can be preferentially selected for or against at culture initiation or at other time points during the process. Additionally, by increasing or decreasing the ratio of anti-CD3 and/or anti-CD28 antibodies on the beads or other surface, subpopulations of T cells can be preferentially selected for or against at culture initiation or at other desired time points.

›ACCTGTGTTGTGTCCCATGAAGATAGCAGGACCCTGCTAAATGCTTCTAGG · 6 of 15

In one embodiment, a T cell population can be selected that expresses one or more of IFN-γ, TNFα, IL-17A, IL-2, IL-3, IL-4, GM-CSF, IL-10, IL-13, granzyme B, and perforin, or other appropriate molecules, e.g., other cytokines. Methods for screening for cell expression can be determined, e.g., by the methods described in PCT Publication No.: WO 2013/126712.

For isolation of a desired population of cells by positive or negative selection, the concentration of cells and surface (e.g., particles such as beads) can be varied. In certain aspects, it may be desirable to significantly decrease the volume in which beads and cells are mixed together (e.g., increase the concentration of cells), to ensure maximum contact of cells and beads. For example, in one aspect, a concentration of 10 billion cells/ml, 9 billion/ml, 8 billion/ml, 7 billion/ml, 6 billion/ml, or 5 billion/ml is used. In one aspect, a concentration of 1 billion cells/ml is used. In yet one aspect, a concentration of cells from 75, 80, 85, 90, 95, or 100 million cells/ml is used. In further aspects, concentrations of 125 or 150 million cells/ml can be used.

Using high concentrations can result in increased cell yield, cell activation, and cell expansion. Further, use of high cell concentrations allows more efficient capture of cells that may weakly express target antigens of interest, such as CD28-negative T cells, or from samples where there are many tumor cells present (e.g., leukemic blood, tumor tissue, etc.). Such populations of cells may have therapeutic value and would be desirable to obtain. For example, using high concentration of cells allows more efficient selection of CD8+ T cells that normally have weaker CD28 expression.

In a related aspect, it may be desirable to use lower concentrations of cells. By significantly diluting the mixture of T cells and surface (e.g., particles such as beads), interactions between the particles and cells is minimized. This selects for cells that express high amounts of desired antigens to be bound to the particles. For example, CD4+ T cells express higher levels of CD28 and are more efficiently captured than CD8+ T cells in dilute concentrations. In one aspect, the concentration of cells used is 5×10 6 /ml. In other aspects, the concentration used can be from about 1×10 5 /ml to 1×10 6 /ml, and any integer value in between.

In other aspects, the cells may be incubated on a rotator for varying lengths of time at varying speeds at either 2-10° C. or at room temperature.

T cells for stimulation can also be frozen after a washing step. Wishing not to be bound by theory, the freeze and subsequent thaw step provides a more uniform product by removing granulocytes and to some extent monocytes in the cell population. After the washing step that removes plasma and platelets, the cells may be suspended in a freezing solution. While many freezing solutions and parameters are known in the art and will be useful in this context, one method involves using PBS containing 20% DMSO and 8% human serum albumin, or culture media containing 10% Dextran 40 and 5% Dextrose, 20% Human Serum Albumin and 7.5% DMSO, or 31.25% Plasmalyte-A, 31.25% Dextrose 5%, 0.45% NaCl, 10% Dextran 40 and 5% Dextrose, 20% Human Serum Albumin, and 7.5% DMSO or other suitable cell freezing media containing for example, Hespan and PlasmaLyte A, the cells then are frozen to −80° C. at a rate of 1° per minute and stored in the vapor phase of a liquid nitrogen storage tank. Other methods of controlled freezing may be used as well as uncontrolled freezing immediately at −20° C. or in liquid nitrogen.

In certain aspects, cryopreserved cells are thawed and washed as described herein and allowed to rest for one hour at room temperature prior to activation using the methods of the present disclosure.

Also contemplated in the context of the disclosure is the collection of blood samples or apheresis product from a subject at a time period prior to when the expanded cells as described herein might be needed. As such, the source of the cells to be expanded can be collected at any time point necessary, and desired cells, such as T cells, isolated and frozen for later use in immune effector cell therapy for any number of diseases or conditions that would benefit from immune effector cell therapy, such as those described herein. In one aspect a blood sample or an apheresis is taken from a generally healthy subject. In certain aspects, a blood sample or an apheresis is taken from a generally healthy subject who is at risk of developing a disease, but who has not yet developed a disease, and the cells of interest are isolated and frozen for later use. In certain aspects, the T cells may be expanded, frozen, and used at a later time. In certain aspects, samples are collected from a patient shortly after diagnosis of a particular disease as described herein but prior to any treatments. In a further aspect, the cells are isolated from a blood sample or an apheresis from a subject prior to any number of relevant treatment modalities, including but not limited to treatment with agents such as natalizumab, efalizumab, antiviral agents, chemotherapy, radiation, immunosuppressive agents, such as cyclosporin, azathioprine, methotrexate, mycophenolate, and FK506, antibodies, or other immunoablative agents such as CAMPATH, anti-CD3 antibodies, cytoxan, fludarabine, cyclosporin, FK506, rapamycin, mycophenolic acid, steroids, FR901228, and irradiation.

In a further aspect of the present disclosure, T cells are obtained from a patient directly following treatment that leaves the subject with functional T cells. In this regard, it has been observed that following certain cancer treatments, in particular treatments with drugs that damage the immune system, shortly after treatment during the period when patients would normally be recovering from the treatment, the quality of T cells obtained may be optimal or improved for their ability to expand ex vivo. Likewise, following ex vivo manipulation using the methods described herein, these cells may be in a preferred state for enhanced engraftment and in vivo expansion. Thus, it is contemplated within the context of the present disclosure to collect blood cells, including T cells, dendritic cells, or other cells of the hematopoietic lineage, during this recovery phase. Further, in certain aspects, mobilization (for example, mobilization with GM-CSF) and conditioning regimens can be used to create a condition in a subject wherein repopulation, recirculation, regeneration, and/or expansion of particular cell types is favored, especially during a defined window of time following therapy. Illustrative cell types include T cells, B cells, dendritic cells, and other cells of the immune system.

›ACCTGTGTTGTGTCCCATGAAGATAGCAGGACCCTGCTAAATGCTTCTAGG · 7 of 15

In one embodiment, the immune effector cells expressing a CAR molecule, e.g., a CAR molecule described herein, are obtained from a subject that has received a low, immune enhancing dose of an mTOR inhibitor. In an embodiment, the population of immune effector cells, e.g., T cells, to be engineered to express a CAR, are harvested after a sufficient time, or after sufficient dosing of the low, immune enhancing, dose of an mTOR inhibitor, such that the level of PD1 negative immune effector cells, e.g., T cells, or the ratio of PD1 negative immune effector cells, e.g., T cells/PD1 positive immune effector cells, e.g., T cells, in the subject or harvested from the subject has been, at least transiently, increased.

In other embodiments, population of immune effector cells, e.g., T cells, which have, or will be engineered to express a CAR, can be treated ex vivo by contact with an amount of an mTOR inhibitor that increases the number of PD1 negative immune effector cells, e.g., T cells or increases the ratio of PD1 negative immune effector cells, e.g., T cells/PD1 positive immune effector cells, e.g., T cells.

In one embodiment, a T cell population is diaglycerol kinase (DGK)-deficient. DGK-deficient cells include cells that do not express DGK RNA or protein, or have reduced or inhibited DGK activity. DGK-deficient cells can be generated by genetic approaches, e.g., administering RNA-interfering agents, e.g., siRNA, shRNA, miRNA, to reduce or prevent DGK expression. Alternatively, DGK-deficient cells can be generated by treatment with DGK inhibitors described herein.

In one embodiment, a T cell population is Ikaros-deficient. Ikaros-deficient cells include cells that do not express Ikaros RNA or protein, or have reduced or inhibited Ikaros activity, Ikaros-deficient cells can be generated by genetic approaches, e.g., administering RNA-interfering agents, e.g., siRNA, shRNA, miRNA, to reduce or prevent Ikaros expression. Alternatively, Ikaros-deficient cells can be generated by treatment with Ikaros inhibitors, e.g., lenalidomide.

In embodiments, a T cell population is DGK-deficient and Ikaros-deficient, e.g., does not express DGK and Ikaros, or has reduced or inhibited DGK and Ikaros activity. Such DGK and Ikaros-deficient cells can be generated by any of the methods described herein.

In an embodiment, the NK cells are obtained from the subject. In another embodiment, the NK cells are an NK cell line, e.g., NK-92 cell line (Conkwest).

In some aspects, the cells of the disclosure (e.g., the immune effector cells of the disclosure, e.g., the CAR-expressing cells of the disclosure) are induced pluripotent stem cells (“iPSCs”) or embryonic stem cells (ESCs), or are T cells generated from (e.g., differentiated from) said iPSC and/or ESC. iPSCs can be generated, for example, by methods known in the art, from peripheral blood T lymphocytes, e.g., peripheral blood T lymphocytes isolated from a healthy volunteer. As well, such cells may be differentiated into T cells by methods known in the art. See e.g., Themeli M. et al., Nat. Biotechnol., 31, pp. 928-933 (2013); doi:10.1038/nbt.2678; WO2014/165707, the contents of each of which are incorporated herein by reference in their entirety.

Additional Expressed Agents

In embodiments, the CAR-expressing immune effector cell described herein can express a CAR comprising a conditional expression domain, for example, as described in WO2017/181119, or a CAR comprising a degradation domain as described in WO2017/024318. In some embodiments, a conditional expression domain may be used with a single CAR (e.g., a single CAR comprising one antigen binding domain, or a single CAR comprising two or more antigen binding domains) or with multiple CARs.

In another embodiment, a CAR-expressing immune effector cell described herein can further express another agent, e.g., an agent which enhances the activity of a CAR-expressing cell. Such additional expressed agents can be introduced together with the CAR, e.g., in the same vector or template nucleic acid, or in a separate vector.

For example, in one embodiment, the agent can be an agent which inhibits an inhibitory molecule. Examples of inhibitory molecules include PD-1, PD-L1, CTLA-4, TIM-3, CEACAM (e.g., CEACAM-1, CEACAM-3 and/or CEACAM-5), LAG-3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4 and TGF beta, e.g., as described herein. In one embodiment, the agent that inhibits an inhibitory molecule comprises a first polypeptide, e.g., an inhibitory molecule, associated with a second polypeptide that provides a positive signal to the cell, e.g., an intracellular signaling domain described herein. In one embodiment, the agent comprises a first polypeptide, e.g., of an inhibitory molecule such as PD-1, PD-L1, CTLA-4, TIM-3, CEACAM (e.g., CEACAM-1, CEACAM-3 and/or CEACAM-5), LAG-3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4 or TGF beta, or a fragment of any of these, and a second polypeptide which is an intracellular signaling domain described herein (e.g., comprising a costimulatory domain (e.g., 41BB, CD27 or CD28, e.g., as described herein) and/or a primary signaling domain (e.g., a CD3 zeta signaling domain described herein). In one embodiment, the agent comprises a first polypeptide of PD-1 or a fragment thereof, and a second polypeptide of an intracellular signaling domain described herein (e.g., a CD28, CD27, OX40 or 4-IBB signaling domain described herein and/or a CD3 zeta signaling domain described herein). In embodiments, the agent comprises a first polypeptide of an extracellular domain of an inhibitory molecule and a second polypeptide of an intracellular signaling domain of a costimulatory molecule described herein or primary signaling molecule described herein. Such molecules in which an inhibitory molecule (e.g., a domain of an inhibitory molecule) is associated with a molecule that provides a positive signal (e.g., a domain of a costimulatory molecule or primary signaling molecule) are further described in, for example, WO2013/019615.

›ACCTGTGTTGTGTCCCATGAAGATAGCAGGACCCTGCTAAATGCTTCTAGG · 8 of 15

In one embodiment, the CAR-expressing immune effector cell described herein can further comprise a second CAR, e.g., a second CAR that includes a different antigen binding domain, e.g., to a different epitope on the same target (e.g., a target described above) or a different target. In one embodiment, the second CAR includes an antigen binding domain to a target expressed on the same cancer cell type as the target of the first CAR. In one embodiment, the CAR-expressing immune effector cell comprises a first CAR that targets a first antigen and includes an intracellular signaling domain having a costimulatory signaling domain but not a primary signaling domain, and a second CAR that targets a second, different, antigen and includes an intracellular signaling domain having a primary signaling domain but not a costimulatory signaling domain.

While not wishing to be bound by theory, placement of a costimulatory signaling domain, e.g., 4-1BB, CD28, CD27 or OX-40, onto the first CAR, and the primary signaling domain, e.g., CD3 zeta, on the second CAR can limit the CAR activity to cells where both targets are expressed. In one embodiment, the CAR expressing immune effector cell comprises a first CAR that includes an antigen binding domain that targets, e.g., a target described above, a transmembrane domain and a costimulatory domain and a second CAR that targets an antigen other than antigen targeted by the first CAR (e.g., an antigen expressed on the same cancer cell type as the first target) and includes an antigen binding domain, a transmembrane domain and a primary signaling domain. In another embodiment, the CAR expressing immune effector cell comprises a first CAR that includes an antigen binding domain that targets, e.g., a target described above, a transmembrane domain and a primary signaling domain and a second CAR that targets an antigen other than antigen targeted by the first CAR (e.g., an antigen expressed on the same cancer cell type as the first target) and includes an antigen binding domain to the antigen, a transmembrane domain and a costimulatory signaling domain.

In one embodiment, the CAR-expressing immune effector cell comprises a CAR described herein, e.g., a CAR to a target described above, and an inhibitory CAR. In one embodiment, the inhibitory CAR comprises an antigen binding domain that binds an antigen found on normal cells but not cancer cells, e.g., normal cells that also express the target. In one embodiment, the inhibitory CAR comprises the antigen binding domain, a transmembrane domain and an intracellular domain of an inhibitory molecule. For example, the intracellular domain of the inhibitory CAR can be an intracellular domain of PD1, PD-L1, CTLA-4, TIM-3, CEACAM (e.g., CEACAM-1, CEACAM-3 and/or CEACAM-5), LAG-3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4 or TGF beta.

In one embodiment, an immune effector cell (e.g., T cell, NK cell) comprises a first CAR comprising an antigen binding domain that binds to a tumor antigen as described herein, and a second CAR comprising a PD1 extracellular domain or a fragment thereof.

In one embodiment, the cell further comprises an inhibitory molecule as described above. Non-limiting examples of inhibitory molecules include PD-1, PD-L1, PD-L2, CTLA4, TIM3, LAG3, CEACAM (e.g., CEACAM-1, CEACAM-3 and/or CEACAM-5), VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, CD80, CD86, B7-H3 (CD276), B7-H4 (VTCN1), HVEM (TNFRSF14 or CD107), KIR, A2aR, MHC class I, MHC class II, GAL9, adenosine, and TGF beta.

In one embodiment, the second CAR in the cell is an inhibitory CAR, wherein the inhibitory CAR comprises an antigen binding domain, a transmembrane domain, and an intracellular domain of an inhibitory molecule. The inhibitory molecule can be chosen from one or more of: PD1, PD-L1, CTLA-4, TIM-3, LAG-3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, TGF beta, CEACAM-1, CEACAM-3, and CEACAM-5. In one embodiment, the second CAR molecule comprises the extracellular domain of PD1 or a fragment thereof.

In embodiments, the second CAR molecule in the cell further comprises an intracellular signaling domain comprising a primary signaling domain and/or an intracellular signaling domain.

In other embodiments, the intracellular signaling domain in the cell comprises a primary signaling domain comprising the functional domain of CD3 zeta and a costimulatory signaling domain comprising the functional domain of 4-1BB.

In one embodiment, the second CAR molecule in the cell comprises the amino acid sequence of SEQ ID NO: 30.

In certain embodiments, the antigen binding domain of the first CAR molecule comprises a scFv and the antigen binding domain of the second CAR molecule does not comprise a scFv. For example, the antigen binding domain of the first CAR molecule comprises a scFv and the antigen binding domain of the second CAR molecule comprises a camelid VHH domain.

In other aspects and embodiments, a cell of the disclosure, e.g., a cell engineered to express a CAR, is also engineered to express a safety molecule, such as a molecule (or set of molecules) which mediates the depleting of the cells, e.g., CAR T cells, when appropriate (e.g., after the T cells have accomplished the anti-tumor function, or if the T cells are causing life-threatening side effects). In one exemplary aspect, the safety molecule a molecule that does not affect the function of the cell, but which can be targeted by another agent, e.g., an antibody or ADC molecule targeting said molecule. One exemplary embodiment of such a molecule is a truncated receptor, e.g., a receptor comprising the extracellular domain and transmembrane domain of a receptor, but lacking all or a substantial portion of the intracellular domain of the receptor. An example is a truncated EGFR receptor, e.g., as described in WO2011/056894. Without being bound by theory, targeting said truncated EGFR receptor with an anti-EGFR antibody, e.g., cetuximab, will deplete cells expressing the truncated EGFR receptor. A second example is a iCasp9 switch polypeptide, e.g., a polypeptide having a dimerization domain, an optional linker, and a caspase domain oriented such that, when expressed in the presence of a dimerization compound in a mammalian host cell, the iCasp9 switch polypeptide homo-dimerizes, resulting in apoptosis of the host cell. In embodiments, the dimerization domain is a FKBP-based dimerization domain, e.g., the sequence harbors a mutation (F37V) which provides a complementary fitting cavity for AP1903 and AP1903-structurally related ligands (such as AP20187), which molecules may act as a dimerization compound. Such iCasp9 switch polypeptides (and associated dimerization compounds) are described in, for example, WO 1997/031899, US2011/286980, WO2014/164348, WO2013/040371, US2013/071414, WO2014/255360, and N Engl J Med. 2011 Nov. 3; 365(18):1673-83. A third example of such a molecule is a molecule targeted by an anti-CD20 antibody, wherein, for example, administering an anti-CD20 antibody (e.g., rituximab) allows said cells to be depleted. Examples of molecules targeted by an anti-CD20 antibody include CD20, and truncated versions thereof (e.g., molecules comprising an extracellular domain recognizable by an anti-CD20 antibody, a transmembrane domain, and lacking at least a portion of an intracellular domain).

›ACCTGTGTTGTGTCCCATGAAGATAGCAGGACCCTGCTAAATGCTTCTAGG · 9 of 15

Split CAR

In some embodiments, the CAR-expressing cell uses a split CAR. The split CAR approach is described in more detail in publications WO2014/055442 and WO2014/055657. Briefly, a split CAR system comprises a cell expressing a first CAR having a first antigen binding domain and a costimulatory domain (e.g., 41BB), and the cell also expresses a second CAR having a second antigen binding domain and an intracellular signaling domain (e.g., CD3 zeta). When the cell encounters the first antigen, the costimulatory domain is activated, and the cell proliferates. When the cell encounters the second antigen, the intracellular signaling domain is activated and cell-killing activity begins. Thus, the CAR-expressing cell is only fully activated in the presence of both antigens.

Multiple CAR Expression

In one aspect, the CAR-expressing cell described herein can further comprise a second CAR (see, e.g., Additional Expressed Agents above), e.g., a second CAR that includes a different antigen binding domain, e.g., to the same target or a different target (e.g., a target other than a cancer associated antigen described herein or a different cancer associated antigen described herein). In one embodiment, the second CAR includes an antigen binding domain to a target expressed by the same cancer cell type as the cancer associated antigen targeted by the first CAR. In one embodiment, the CAR-expressing cell comprises a first CAR that targets a first antigen and includes an intracellular signaling domain having a costimulatory signaling domain but not a primary signaling domain, and a second CAR that targets a second, different, antigen and includes an intracellular signaling domain having a primary signaling domain but not a costimulatory signaling domain. While not wishing to be bound by theory, placement of a costimulatory signaling domain, e.g., 4-1BB, CD28, CD27 or OX-40, onto the first CAR, and the primary signaling domain, e.g. CD3 zeta, on the second CAR can limit the CAR activity to cells where both targets are expressed. In one embodiment, the CAR expressing cell comprises a first cancer associated antigen CAR that includes an antigen binding domain that binds a target antigen described herein, a transmembrane domain and a costimulatory domain and a second CAR that targets a different target antigen (e.g., an antigen expressed on that same cancer cell type as the first target antigen) and includes an antigen binding domain, a transmembrane domain and a primary signaling domain. In another embodiment, the CAR expressing cell comprises a first CAR that includes an antigen binding domain that binds a target antigen described herein, a transmembrane domain and a primary signaling domain and a second CAR that targets an antigen other than the first target antigen (e.g., an antigen expressed on the same cancer cell type as the first target antigen) and includes an antigen binding domain to the antigen, a transmembrane domain and a costimulatory signaling domain.

In some embodiments, the CAR-expressing cell comprises a first and second CAR, wherein the antigen binding domain of one of said first CAR said second CAR does not comprise a variable light domain and a variable heavy domain. In some embodiments, the antigen binding domain of one of said first CAR said second CAR is an scFv, and the other is not an scFv. In some embodiments, the antigen binding domain of one of said first CAR said second CAR comprises a single VH domain, e.g., a camelid, shark, or lamprey single VH domain, or a single VH domain derived from a human or mouse sequence. In some embodiments, the antigen binding domain of one of said first CAR said second CAR comprises a nanobody. In some embodiments, the antigen binding domain of one of said first CAR said second CAR comprises a camelid VHH domain.

Telomerase Expression

While not wishing to be bound by any particular theory, in some embodiments, a therapeutic T cell has short term persistence in a patient, due to shortened telomeres in the T cell; accordingly, transfection with a telomerase gene can lengthen the telomeres of the T cell and improve persistence of the T cell in the patient. See Carl June, “Adoptive T cell therapy for cancer in the clinic”, Journal of Clinical Investigation, 117:1466-1476 (2007). Thus, in an embodiment, an immune effector cell, e.g., a T cell, as disclosed herein can further comprise an ectopically expressed telomerase subunit, e.g., the catalytic subunit of telomerase, e.g., TERT, e.g., hTERT. In some aspects, this disclosure provides a method of producing a CAR-expressing cell with longer persistence in a patient, comprising contacting a cell with a nucleic acid encoding a telomerase subunit, e.g., the catalytic subunit of telomerase, e.g., TERT, e.g., hTERT. The cell may be contacted with the nucleic acid before, simultaneous with, or after being contacted with a construct encoding a CAR.

In embodiments in which a cell is engineered to express more than one molecule, the sequence encoding each of said molecules (e.g., sequence encoding a CAR and sequence encoding an NK inhibitory molecule) can be disposed on the same nucleic acid molecule (e.g., same template nucleic acid), e.g., the same plasmid or vector, e.g., viral vector, e.g., lentiviral vector. In an embodiment, (i) sequence encoding a CAR, as described herein, and (ii) sequence encoding an NK inhibitory molecule, as described herein, can be present on the same nucleic acid, e.g., vector. Production of the corresponding proteins can be achieved, e.g., by the use of separate promoters, or by the use of a bicistronic transcription product (which can result in the production of two proteins by cleavage of a single translation product or by the translation of two separate protein products). In an embodiment, a sequence encoding a cleavable peptide, e.g., a P2A, T2A or F2A sequence, is disposed between (i) and (ii). In an embodiment, a sequence encoding an IRES, e.g., an EMCV or EV71 IRES, is disposed between (i) and (ii). In these embodiments, (i) and (ii) are transcribed as a single RNA. In other aspects, each molecule may be expressed from a different promoter. In an embodiment, a first promoter is operably linked to (i) and a second promoter is operably linked to (ii), such that (i) and (ii) are transcribed as separate mRNAs.

›ACCTGTGTTGTGTCCCATGAAGATAGCAGGACCCTGCTAAATGCTTCTAGG · 10 of 15

Alternatively, the sequence encoding the more than one molecules can be disposed on the different nucleic acid molecules (e.g., different template nucleic acid molecules), e.g., different plasmids or vectors, e.g., viral vector, e.g., lentiviral vector. E.g., the (i) sequence encoding a CAR as described herein can be present on a first nucleic acid, e.g., a first vector, and the (ii) sequence encoding a NK inhibitory molecule can be present on the second nucleic acid, e.g., the second vector. In various embodiments, the sequences below may be used.

VI. Cells

In various embodiments, provided herein are cells, e.g., T or NK cells, e.g., autologous or allogeneic T cells. In some embodiments, the cell expresses at least one CAR as described herein. In some embodiments, the at least one CAR is BCMA. In some embodiments, the at least one CAR is CD19. In some embodiments, the CAR is encoded and expressed from a genomic insertion at or near the TET2 gene in the cell, e.g., at or near an intron or intron-exon junction, e.g., the intron between exons 9 and 10 of TET2. In some embodiments, the cell expresses at least one CAR and has reduced, disrupted, or eliminated expression of at least one gene that regulates MHC I expression, e.g., MHC I HLA-A, HLA-B, HLA-C, B2M, NLRC5, and/or MHC II expression, e.g., MHC II HLA-DM, HLA-DO, HLA-DR, HLA-DQ, HLA-DP, CIITA, RFXANK, RFXAP, RFX1, RFX5, NF-YA, NF-YB, NF-YC, X2BP, OCAB. In some embodiments, the cell is generated using a CRISPR system as described herein. Other methods for generating said cells may also be used.

In an aspect, the disclosure provides for cells comprising a gene editing system, e.g., a CRISPR system, described herein. In an aspect, the disclosure provides for cells modified by a gene editing system, e.g., a CRISPR system, described herein.

In another aspect, the disclosure provides cells which comprise, or which at any time comprised, a gRNA molecule, e.g., one or more gRNA molecules, as described herein, or a CRISPR system as described herein. In an embodiment, the cell has been altered, e.g., the target sequence targeted by the gRNA molecule has been altered, e.g., to create an indel, by introduction of a gRNA molecule as described herein (or nucleic acid encoding said gRNA molecule), or a CRISPR system (or nucleic acid encoding one or more components of said CRISPR system) as described herein, e.g., altered by a method described herein. In an embodiment, the alteration results in a change in transcription or translation of the functional (e.g., wild type) gene product of the gene comprising the target site. In an embodiment, the alteration results in reduced or no expression of the functional (e.g., wild type) gene product of the gene comprising the target site. In embodiments, the alteration is insertion of heterologous nucleic acid sequence, e.g., from a template nucleic acid (e.g., as described herein), e.g., sequence encoding a CAR (e.g., as described herein). In embodiments, the alteration results in reduced or no expression of the functional (e.g., wild type) gene product of the gene comprising the target site and insertion of heterologous nucleic acid sequence, e.g., from a template nucleic acid at the same target site. In embodiments, the alteration results in reduced or no expression of the functional (e.g., wild type) gene product of the gene comprising the target site and insertion of heterologous nucleic acid sequence, e.g., from a template nucleic acid at a different target site.

In one aspect, the cell is an animal cell. In embodiments, the cell is a mammalian, primate, or human cell. In embodiments, the cell is a human cell. In embodiments, the cell is an immune effector cell (e.g., a population of immune effector cells), for example a T cell or NK cell. In embodiments, the T cell (e.g., population of T cells) is or comprises a CD4+ T cell, a CD8+ T cell, or a combination thereof. In embodiments, the cell is autologous. In embodiments, the cell is allogeneic.

In a preferred embodiment the cell (or the population of cells) has been, or will be, engineered to express a chimeric antigen receptor (CAR), e.g., a CAR as described in Section V. In embodiments, the cell is engineered to express a BCMA CAR, e.g., as described herein. In embodiments, the CAR-engineered cell is allogeneic. In embodiments, the CAR-engineered cell is autologous. In embodiments, the sequence encoding the CAR is stably integrated into the genome of the cell within a TET2 intron, e.g., at or near a target sequence of a gRNA molecule described herein. In embodiments, the nucleic acid sequence integrated into said site does not comprise sequence of a lentivirus vector (e.g., does not comprise a cPPT or CPT element).

In another aspect, the disclosure provides cells, such as those described above, which include, has at any time included, or will include a second gRNA molecule as described herein, e.g., a second gRNA molecule with a targeting domain different from that of the first gRNA molecule. In embodiments, the two gRNA molecules are complementary to target sites within the same TET2 intron. In other embodiments, the two or more gRNA molecules are complementary to target sequences in different genes. In embodiments, at least one of said gRNA molecules comprises a targeting domain complementary to a TET2 intron sequence, e.g., as described herein. In embodiments, the one or more other gRNA molecules target sequences within an inhibitory molecule gene (e.g., PDCD1), an allogeneic T cell target (e.g., B2M, CIITA, RFXANK, RFXAP, RFX1, RFX5, or a component of the T cell receptor, e.g., TRAC, TRBC, CD3E, CD3D, or CD3G, or combinations thereof).

It will be understood that in any of the disclosed aspects and embodiments in which two or more target sites of different genes (or different molecular complexes, e.g., when targeting a TET2 intron, a component of the T cell receptor, and B2M) are targeted, that for any or all of the different gene (or molecular complex) targets, two or more gRNAs may be employed with respect to one or more of said different genes or different molecular complexes.

›ACCTGTGTTGTGTCCCATGAAGATAGCAGGACCCTGCTAAATGCTTCTAGG · 11 of 15

Additionally or alternatively, when gRNA molecules targeting more than one gene are employed, they may be employed for different means. For example, one may utilize a gRNA molecule to a TET2 intron in conjunction with a template nucleic acid to insert heterologous nucleic acid sequence at or near the target sequence within the TET2 intron. At the same time, one may further utilize one or more additional gRNA molecules to one or more additional targets, e.g., to a component of the T cell receptor (e.g., TRAC), B2M and/or CIITA, to reduce or eliminate expression and/or function of said one or more genes. These additional gRNA molecules may be utilized at the same time, subsequently, or prior to the first gRNA molecule.

In some embodiments, the two or more, e.g. two, gRNA molecules are complementary to target sites within different genes. Such cells may comprise alterations, e.g., indels, at or near each target site such that expression of the functional gene product of more than one gene is reduced or eliminated. As discussed above, in such embodiments, more than one gRNA molecule targeted to each of the different genes may be employed.

In embodiments, the cell comprises, has comprised or will comprise a first gRNA molecule comprising a targeting domain complementary with a target sequence of a TET2 intron or intron-exon junction (e.g., a targeting domain described in Tables 1, or 2). The cell may also comprise, or at any time has comprised or will comprise, a second gRNA molecule comprising a targeting domain complementary with a target sequence of an inhibitory molecule and/or a third gRNA molecule comprising a targeting domain complementary to a target sequence of TRAC, TRBC1, TRBC2, CD247, CD3D, CD3E, or CD3G, and/or a fourth gRNA molecule comprising a targeting domain complementary with a target sequence of B2M, NLRC5, HLA-A, HLA-B or HLA-C, and/or a 5 th gRNA molecule comprising a targeting domain complementary with a target sequence of CIITA. In embodiments the cell comprises heterologous nucleic acid sequence, e.g., sequence encoding a CAR, e.g., as described herein, integrated at or near a site targeted by the gRNA molecule to TET2, and optionally, has reduced or eliminated expression of one or more genes, e.g., one or more genes targeted by the second, third, fourth and/or fifth gRNA molecules.

In embodiments, a cell, e.g., a CAR-expressing cell as described herein, may comprises one or more modifications (e.g., heterologous nucleic acid sequence insertion, or nucleotide insertions or deletions) to an intron of TET2; one or more modifications (e.g., nucleotide insertions or deletions) to an endogenous gene encoding a component of the T cell receptor (e.g., TRAC or TRBC); one or more modifications (e.g., nucleotide insertions or deletions) to an endogenous B2M gene; and/or one or more modifications (e.g., nucleotide insertions or deletions) to an endogenous CIITA gene. In embodiments, one or more of said modifications reduce or eliminate expression of said gene. In embodiments, the disclosure provides a cell, e.g., a CAR-expressing cell, e.g., as described herein, with a modification to a TET2 intron that is further TCR- (e.g., has a level of expression of TCR greater than 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% lower than that of an unmodified cell of the same type, as detected by FACS, e.g., FACS using an anti-CD3 antibody), B2M- (e.g., has a level of expression of B2M and/or one or more MHC class I proteins greater than 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% lower than that of an unmodified cell of the same type, as detected by FACS, e.g., FACS using an anti-B2M antibody) and/or CIITA- (e.g., has a level of expression of CIITA and/or a MHC class II protein greater than 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% lower than that of an unmodified cell of the same type, as detected by FACS, e.g., FACS using an anti-CIITA antibody). In an embodiment, the cell is engineered to express a CAR molecule, e.g., as described herein. In embodiments, the CAR is a CD19 CAR, e.g., as described herein. In other embodiments, the CAR is a BCMA CAR, e.g., as described herein. In other embodiments, the CAR is a CD123 CAR, e.g., as described herein.

In an aspect, a cell of the disclosure comprises (or a population of cells comprises one or more cells which comprise):

(a) Nucleic acid sequence encoding a CAR, e.g., a template nucleic acid comprising sequence encoding a CAR, e.g., as described herein, e.g., wherein said nucleic acid sequence encoding the CAR is (or becomes) integrated into the genome at a site at or near the target sequence of a TET2 intron gRNA molecule described herein (e.g., a gRNA molecule comprising a targeting domain of Table 1 or Table 2);

Wherein the cell (or population of cells comprises one or more cells which) expresses the CAR. In embodiments, the nucleic acid sequence encoding the CAR is integrated in only one allele of the target sequence. In embodiments, one or more functions of TET2 is reduced or eliminated in said cell. In embodiments, one or more functions of TET2 is reduced, e.g., reduced by 10%, 20%, 30%, 40%, 50%, 60% or more, but not eliminated.

In an aspect, a cell of the disclosure comprises (e.g., a population of cells of the disclosure comprises one or more cells which comprise):

(b) Nucleic acid sequence encoding a CAR, e.g., a template nucleic acid comprising sequence encoding a CAR, e.g., as described herein, e.g., wherein said nucleic acid sequence encoding the CAR is (or becomes) integrated into the genome at a site at or near the target sequence of a TET2 intron gRNA molecule described herein (e.g., a gRNA molecule comprising a targeting domain of Table 1 or Table 2); (c) An indel at or near a sequence of a gene encoding a component of a TCR (e.g., TRAC, TRBC1 or TRBC2, e.g. TRAC) or its regulatory elements, e.g., an indel at or near a target sequence of a gRNA comprising a targeting domain to a component of a TCR (e.g., TRAC, TRBC1 or TRBC2, e.g. TRAC); (d) An indel at or near a sequence of the gene encoding B2M or its regulatory elements, e.g., an indel at or near a target sequence of a gRNA comprising a targeting domain to B2M; and

›ACCTGTGTTGTGTCCCATGAAGATAGCAGGACCCTGCTAAATGCTTCTAGG · 12 of 15

Optionally, an indel at or near a sequence of the gene encoding CIITA or its regulatory elements, e.g., an indel at or near a target sequence of a gRNA comprising a targeting domain to CIITA; wherein the cell (or population of cells comprises one or more cells which) expresses the CAR, and exhibits reduced or eliminated expression and/or function of one or more of: i) a component of a TCR (e.g., TRAC, TRBC1 or TRBC2, e.g. TRAC), ii) B2M, and/or iii) CIITA

In any of the aforementioned embodiments and aspects the cell comprises one or more CRISPR systems, e.g., as described herein, comprising the gRNA molecule(s) indicated. In embodiments, the cell comprises one or more ribonuclear protein (RNP) complexes each comprising a Cas9 molecule, e.g., as described herein, and a gRNA molecule comprising the indicated targeting domain, e.g., as described herein. In embodiments, including in any of the methods described herein, where gRNAs to more than one target sequence are employed, the gRNAs (and CRISPR systems comprising said gRNAs) may be introduced into the cell simultaneously. In other embodiments, including in any of the methods described herein, where gRNAs to more than one target sequence are employed, the gRNAs (and CRISPR systems comprising said gRNAs) may be introduced into the cell sequentially.

In an aspect involving any of the aforementioned embodiments or aspects, the population of cells comprises at least 20%, e.g., at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99%, of cells which include an insertion of nucleic acid sequence encoding the CAR at or near the target sequence of a gRNA targeting a TET2 intron or intron-exon junction (as described herein), e.g., include an insertion of nucleic acid sequence encoding the CAR at or near the target sequence of a gRNA targeting a TET2 intron or intron-exon junction (as described herein) at only one allele. In an aspect involving any of the aforementioned embodiments or aspects, the population of cells comprises at least 20%, e.g., at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99%, of cells which include an indel at or near each of the target sequences targeted by each of the gRNA molecules. Said population may be obtained, for example, by utilizing high efficiency gRNA molecules (e.g., gRNA molecules which cause an indel in >85% of said cells which are exposed to said gRNA molecule), or by enriching the population for the desired cell, e.g., by selecting for the desired cell population, e.g., by affinity chromatography or cell sorting.

VII. Template Nucleic Acids (For Modification of Nucleic Acid Sequence)

In an aspect, the disclosure provides for insertion of nucleic acid sequence, e.g., nucleic acid sequence from a template nucleic acid, at or near a target sequence recognized by a CRISPR system, e.g., a CRISPR system comprising a gRNA molecule to a tet2 intron, e.g., to the intron between exon 9 and exon 10 of the tet2 gene, e.g., described herein. In an embodiment, nucleic acid sequence at or near the target sequence is modified to have some or all of the sequence of the template nucleic acid, typically at or near cleavage site(s). In an embodiment, the template nucleic acid is single stranded. In an alternate embodiment, the template nucleic acid is double stranded. In an embodiment, the template nucleic acid is DNA, e.g., double stranded DNA. In an alternate embodiment, the template nucleic acid is single stranded DNA.

In embodiments, the template nucleic acid comprises sequence encoding a first heterologous protein, for example, a chimeric antigen receptor (CAR), e.g., a CAR as described above in section V. In some embodiments, the template nucleic acid further comprises another nucleic acid sequence encoding a second heterologous protein. In some embodiments, the sequence encoding the first heterologous protein and the sequence encoding the second heterologous protein are transcribed as a single transcript. In embodiments, two (or more) proteins of interest may be separated from each other by inclusion of an intervening cleavage site, such as a 2A cleavage site. In other embodiments, the template nucleic acid includes an internal ribosomal entry site (IRES), such that the two (or more) proteins are produced as separate proteins from the same mRNA. Examples of 2A cleavage sites that can be used as described herein are shown below:

2A Peptide: Amino acid sequence*

T2A:

(SEQ ID NO: 130)

(GSG) E G R G S L L T C G D V E E N P G P

P2A:

(SEQ ID NO: 131)

(GSG) A T N F S L L K Q A G D V E E N P G P

E2A:

(SEQ ID NO: 132)

(GSG) Q C T N Y A L L K L A G D V E S N P G P

F2A:

(SEQ ID NO: 133)

(GSG) V K Q T L N F D L L K L A G D V E S N P G P

(GSG) sequence is optional, and can be added to the 5′ end of the 2A sequence to improve cleavage in some contexts.

In an embodiment, the template nucleic acid alters the structure of the target position by participating in an insertion event, e.g., a homology directed repair event. In an embodiment, the template nucleic acid alters the sequence of the target position, for example by insertion of part or all of the template nucleic acid sequence at or near the target sequence. In an embodiment, the template nucleic acid results in the incorporation of a modified or non-naturally occurring base at or near the target sequence.

Mutations in a gene or pathway described herein may be corrected using one of the approaches discussed herein. In an embodiment, a mutation in a gene or pathway described herein is corrected by homology directed repair (HDR) using a template nucleic acid. In an embodiment, a mutation in a gene or pathway described herein is corrected by homologous recombination (HR) using a template nucleic acid. In an embodiment, a mutation in a gene or pathway described herein is corrected by Non-Homologous End Joining (NHEJ) repair using a template nucleic acid. In other embodiments, nucleic acid encoding molecules of interest may be inserted at or near a site modified by a CRISPR system of the present disclosure. In an embodiment, the nucleic acid inserted encodes a chimeric antigen receptor as described herein. In embodiments, the template nucleic acid comprises regulatory elements, e.g., one or more promotors and/or enhancers, operably linked to the nucleic acid sequence encoding a molecule of interest, e.g., a chimeric antigen receptor, e.g., as described herein.

›ACCTGTGTTGTGTCCCATGAAGATAGCAGGACCCTGCTAAATGCTTCTAGG · 13 of 15

HDR Repair and/or Insertion, and Template Nucleic Acids

As described herein, nuclease-induced homology directed repair (HDR) can be used to alter a target sequence (e.g., insert heterologous nucleic acid, e.g., insert nucleic acid encoding a heterologous protein) and/or correct (e.g., repair or edit) a mutation in the genome. While not wishing to be bound by theory, it is believed that alteration of the target sequence occurs by homology-directed repair (HDR) with a donor template or template nucleic acid. For example, the donor template or the template nucleic acid provides for alteration of the target sequence. It is contemplated that a plasmid donor can be used as a template for homologous recombination. It is contemplated that a vector can be used as a template nucleic acid, or can provide the template nucleic acid to a cell of interest. Exemplary vectors include lentiviral vectors, mRNA, adenoviral vectors, adenoassociated viral vectors (AAV), minicircles, and nanoplasmids. In an embodiment, the template nucleic acid is delivered by a recombinant AAV. In some embodiments, the AAV does not incorporate its genome into that of a host cell, e.g., a target cell, e.g., an immune effector cell, e.g., a T cell, e.g., as describe herein. In some embodiments, the AAV can incorporate its genome into that of the host cell. In some embodiments, the AAV is a self-complementary adenoassociated virus (scAAV), e.g., a scAAV that packages both strands which anneal together to form double stranded DNA. In an embodiment, an AAV capsid that can be used in the methods described herein is a capsid sequence from serotype AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV.rh8, AAV.rh10, AAV rh32/33, AAV.rh43, AAV.rh64R1, or AAV7m8. In an embodiment, the template nucleic acid is delivered in a re-engineered AAV capsid, e.g., with 50% or greater, e.g., 60% or greater, 70% or greater, 80% or greater, 90% or greater, or 95% or greater, sequence homology with a capsid sequence from serotypes AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV.rh8, AAV.rh10, AAV.rh32/33, AAV.rh43, or AAV. rh64R1. In an embodiment, the template nucleic acid is delivered by a chimeric AAV capsid. Exemplary chimeric AAV capsids include, but are not limited to, AAV9i1, AAV2i8, AAV-DJ, AAV2G9, AAV2i8G9, or AAV8G9. In a preferred embodiment, the vector is an AAV6 vector or reengineered AAV6 vector. It is further contemplated that a single stranded donor template can be used as a template for alteration of the target sequence by alternate methods of homology directed repair (e.g., single strand annealing) between the target sequence and the template nucleic acid. Template nucleic acid-effected alteration of a target sequence depends on cleavage by a Cas9 molecule. Cleavage by Cas9 can comprise a double strand break or two single strand breaks.

In an embodiment, a mutation can be corrected or nucleic acid sequence inserted by either a single double-strand break or two single strand breaks. In an embodiment, a mutation can be corrected or nucleic acid sequence inserted by (1) a single double-strand break, (2) two single strand breaks, (3) two double stranded breaks with a break occurring on each side of the target sequence, (4) one double stranded breaks and two single strand breaks with the double strand break and two single strand breaks occurring on each side of the target sequence or (5) four single stranded breaks with a pair of single stranded breaks occurring on each side of the target sequence.

Double Strand Break Mediated Correction or Insertion

In an embodiment, double strand cleavage is effected by a Cas9 molecule having the ability to cleave both strands of DNA, for example, having cleavage activity associated with an HNH-like domain and cleavage activity associated with a RuvC-like domain, e.g., an N-terminal RuvC-like domain, e.g., a wild type Cas9. Such embodiments require only a single gRNA.

Single Strand Break Mediated Correction or Insertion

In other embodiments, two single strand breaks, or nicks, are effected by a Cas9 molecule having nickase activity, e.g., cleavage activity associated with an HNH-like domain or cleavage activity associated with an N-terminal RuvC-like domain. Such embodiments require two gRNAs, one for placement of each single strand break. In an embodiment, the Cas9 molecule having nickase activity cleaves the strand to which the gRNA hybridizes, but not the strand that is complementary to the strand to which the gRNA hybridizes. In an embodiment, the Cas9 molecule having nickase activity does not cleave the strand to which the gRNA hybridizes, but rather cleaves the strand that is complementary to the strand to which the gRNA hybridizes.

In an embodiment, the nickase has HNH activity, e.g., a Cas9 molecule having the RuvC activity inactivated, e.g., a Cas9 molecule having a mutation at D10, e.g., the D10A mutation. D10A inactivates RuvC; therefore, the Cas9 nickase has (only) HNH activity and will cut on the strand to which the gRNA hybridizes (e.g., the complementary strand, which does not have the NGG PAM on it). In other embodiments, a Cas9 molecule having an H840, e.g., an H840A, mutation can be used as a nickase. H840A inactivates HNH; therefore, the Cas9 nickase has (only) RuvC activity and cuts on the non-complementary strand (e.g., the strand that has the NGG PAM and whose sequence is identical to the gRNA).

In an embodiment, in which a nickase and two gRNAs are used to position two single strand nicks, one nick is on the + strand and one nick is on the − strand of the target nucleic acid. The PAMs are outwardly facing. The gRNAs can be selected such that the gRNAs are separated by, from about 0-50, 0-100, or 0-200 nucleotides. In an embodiment, there is no overlap between the target sequence that is complementary to the targeting domains of the two gRNAs. In an embodiment, the gRNAs do not overlap and are separated by as much as 50, 100, or 200 nucleotides. In an embodiment, the use of two gRNAs can increase specificity, e.g., by decreasing off-target binding (Ran el al., CELL 2013).

›ACCTGTGTTGTGTCCCATGAAGATAGCAGGACCCTGCTAAATGCTTCTAGG · 14 of 15

In an embodiment, a single nick can be used to induce HDR. It is contemplated herein that a single nick can be used to increase the ratio of HDR, HR or NHEJ at a given cleavage site.

Placement of the Double Strand Break or a Single Strand Break Relative to Target Position

The double strand break or single strand break in one of the strands should be sufficiently close to target position such that correction or insertion occurs at or near said target position. In an embodiment, the distance is not more than 50, 100, 200, 300, 350 or 400 nucleotides. While not wishing to be bound by theory, it is believed that the break should be sufficiently close to target position such that the break is within the region that is subject to exonuclease-mediated removal during end resection. If the distance between the target position and a break is too great, the mutation may not be included in the end resection and, therefore, may not be corrected, as donor sequence may only be used to correct sequence within the end resection region. For insertion, the distance between the target position (i.e., the position where the heterologous sequence is desired to be inserted) and the break should also be sufficiently close.

In an embodiment, in which a gRNA (e.g., sgRNA or dgRNA) and Cas9 nuclease induce a double strand break for the purpose of inducing HDR- or HR-mediated correction or insertion, the cleavage site is between 0-200 bp (e.g., 0 to 175, 0 to 150, 0 to 125, 0 to 100, 0 to 75, 0 to 50, 0 to 25, 25 to 200, 25 to 175, 25 to 150, 25 to 125, 25 to 100, 25 to 75, 25 to 50, 50 to 200, 50 to 175, 50 to 150, 50 to 125, 50 to 100, 50 to 75, 75 to 200, 75 to 175, 75 to 150, 75 to 125, 75 to 100 bp) away from the target position. In an embodiment, the cleavage site is between 0-100 bp (e.g., 0 to 75, 0 to 50, 0 to 25, 25 to 100, 25 to 75, 25 to 50, 50 to 100, 50 to 75 or 75 to 100 bp) away from the target position.

In an embodiment, in which two gRNAs (independently, unimolecular (or chimeric) or modular gRNA) complexing with Cas9 nickases induce two single strand breaks for the purpose of inducing HDR-mediated correction or insertion, the closer nick is between 0-200 bp (e.g., 0 to 175, 0 to 150, 0 to 125, 0 to 100, 0 to 75, 0 to 50, 0 to 25, 25 to 200, 25 to 175, 25 to 150, 25 to 125, 25 to 100, 25 to 75, 25 to 50, 50 to 200, 50 to 175, 50 to 150, 50 to 125, 50 to 100, 50 to 75, 75 to 200, 75 to 175, 75 to 150, 75 to 125, 75 to 100 bp) away from the target position and the two nicks will ideally be within 25-55 bp of each other (e.g., 25 to 50, 25 to 45, 25 to 40, 25 to 35, 25 to 30, 30 to 55, 30 to 50, 30 to 45, 30 to 40, 30 to 35, 35 to 55, 35 to 50, 35 to 45, 35 to 40, 40 to 55, 40 to 50, 40 to 45 bp) and no more than 100 bp away from each other (e.g., no more than 90, 80, 70, 60, 50, 40, 30, 20, 10 or 5 bp away from each other). In an embodiment, the cleavage site is between 0-100 bp (e.g., 0 to 75, 0 to 50, 0 to 25, 25 to 100, 25 to 75, 25 to 50, 50 to 100, 50 to 75 or 75 to 100 bp) away from the target position.

In one embodiment, two gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position a double-strand break on both sides of a target position. In an alternate embodiment, three gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position a double strand break (i.e., one gRNA complexes with a Cas9 nuclease) and two single strand breaks or paired single stranded breaks (i.e., two gRNAs complex with Cas9 nickases) on either side of the target position (e.g., the first gRNA is used to target upstream (i.e., 5′) of the target position and the second gRNA is used to target downstream (i.e., 3′) of the target position). In another embodiment, four gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to generate two pairs of single stranded breaks (i.e., two pairs of two gRNAs complex with Cas9 nickases) on either side of the target position (e.g., the first gRNA is used to target upstream (i.e., 5′) of the target position and the second gRNA is used to target downstream (i.e., 3′) of the target position). The double strand break(s) or the closer of the two single strand nicks in a pair will ideally be within 0-500 bp of the target position (e.g., no more than 450, 400, 350, 300, 250, 200, 150, 100, 50 or 25 bp from the target position). When nickases are used, the two nicks in a pair are within 25-55 bp of each other (e.g., between 25 to 50, 25 to 45, 25 to 40, 25 to 35, 25 to 30, 50 to 55, 45 to 55, 40 to 55, 35 to 55, 30 to 55, 30 to 50, 35. to 50, 40 to 50, 45 to 50, 35 to 45, or 40 to 45 bp) and no more than 100 bp away from each other (e.g., no more than 90, 80, 70, 60, 50, 40, 30, 20 or 10 bp).

In one embodiment, two gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position a double-strand break on both sides of a target position. In an alternate embodiment, three gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position a double strand break (i.e., one gRNA complexes with a Cas9 nuclease) and two single strand breaks or paired single stranded breaks (i.e., two gRNAs complex with Cas9 nickases) on two target sequences (e.g., the first gRNA is used to target an upstream (i.e., 5′) target sequence and the second gRNA is used to target a downstream (i.e., 3′) target sequence of an insertion site. In another embodiment, four gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to generate two pairs of single stranded breaks (i.e., two pairs of two gRNAs complex with Cas9 nickases) on either side of an insertion site (e.g., the first gRNA is used to target an upstream (i.e., 5′) target sequence described herein, and the second gRNA is used to target a downstream (i.e., 3′) target sequence described herein). The double strand break(s) or the closer of the two single strand nicks in a pair will ideally be within 0-500 bp of the target position (e.g., no more than 450, 400, 350, 300, 250, 200, 150, 100, 50 or 25 bp from the target position). When nickases are used, the two nicks in a pair are within 25-55 bp of each other (e.g., between 25 to 50, 25 to 45, 25 to 40, 25 to 35, 25 to 30, 50 to 55, 45 to 55, 40 to 55, 35 to 55, 30 to 55, 30 to 50, 35 to 50, 40 to 50, 45 to 50, 35 to 45, or 40 to 45 bp) and no more than 100 bp away from each other (e.g., no more than 90, 80, 70, 60, 50, 40, 30, 20 or 10 bp).

›ACCTGTGTTGTGTCCCATGAAGATAGCAGGACCCTGCTAAATGCTTCTAGG · 15 of 15

Length of the Homology Arms

In embodiments, incorporation of the heterologous sequence may be facilitated by including in the template nucleic acid one or more, e.g., two (e.g., a 5′ and a 3′), homology arms having homology to sequence at or near, e.g., adjacent to, the target sequence or double strand break, e.g., homology arms having homology to sequence within a TET2 intron, or to sequence comprising sequence within a TET2 intron. The homology arm should extend at least as far as the region in which end resection may occur, e.g., in order to allow the resected single stranded overhang to find a complementary region within the donor template. The overall length could be limited by parameters such as plasmid size or viral packaging limits. In an embodiment, a homology arm does not extend into repeated elements, e.g., ALU repeats, LINE repeats. A template may have two homology arms of the same or different lengths.

In one embodiment, the homology arm comprises, e.g., consists of, the sequence below (SEQ ID NO: 124):

GAATTCCTGTTGCAAAGTGACCTGCTTTGGCATAACTAGCACTCTCATGAT
AGGTTGGCACATTAGTTTCCTGTCAATTGTGTTGACAAGCACATGAGAATC
ATGGAAATCCTTGGTGTTAATCTAAACCAGTGACTATGCATTGCCAGTTAC
AGTTAACTTCCAGGAAAATCTCAAAATTCAGTGCCAGTTACCTGGTAGATT
GTAATCAGTTAAGCAAAAAGCCAAATACAAGCCATTCACCTTACAGAGAGA
GAAGCATATTCACCTTACAGAGAGAGAAGCATAAATGAGAAACACATCATC
ATTGTCACAGTAACTGTGGTAACCTATTGTAAAAGATTCACAGTGCAAAAG
›AGCCTGACTACATATTACAGTGGGTAAAATGGATCGGTCTTGTA

In one embodiment, the homology arm comprises, e.g., consists of, the sequence below (SEQ ID NO: 125):

TGAGGGGAAAATAGATACATGTTATATATATATATATATATATATATGTTC
TATACCAACAAAGGGTTCAGGGTATAATTTTGCATGTAAAGGGGTGACCCA
GAGTAGAGATAAAGAACAAAATATTCTGTTGAAAAAACTATGAATCAATCA
ACCTAATGAATTATCAACATGGATGTAGGTGTAGTTGAAGAAGATGGTCAG
TGAGAATATGGAAACAGATATCAGGAATTAAAGTCATATTCTAGGGCAGAA
AAGCATTCATGGAGGTATTAGATGATAGCTGAAGTAATTTGAAGAAGCTGG
›TGTGAA · 1 of 11

In one embodiment, the first homology arm comprises SEQ ID NO: 124, and the second homology arm comprises SEQ ID NO: 125. In embodiments, a template nucleic acid comprising homology arms comprising SEQ ID NO: 124 and/or SEQ ID NO: 125 is used in conjunction with a CRISPR system comprising a gRNA molecule comprising SEQ ID NO: 10148, 10149 or 10206. In embodiments, a template nucleic acid comprising homology arms comprising SEQ ID NO: 124 and/or SEQ ID NO: 125 is used in conjunction with a CRISPR system comprising a gRNA molecule comprising SEQ ID NO: 10148 or 10149. In embodiments the template nucleic acid is comprised in an AAV vector, e.g., an AAV6 vector.

Exemplary homology arm lengths include at least about 25, 50, 100, 200, 250, 500, 750, 1000, or 1500 nucleotides. In some embodiments, a homology arm length of about 200 nucleotides or less may be used, e.g., if there are regions of repeats present within the genomic region of homology which would otherwise be targeted by a longer homology arm. “Target position,” as used herein, refers to a site on a target nucleic acid (e.g., the chromosome) that is modified by a Cas9 molecule-dependent process. For example, the target position can be a modified Cas9 molecule cleavage of the target nucleic acid and template nucleic acid directed modification, e.g., correction or insertion, of the target position. In an embodiment, a target position can be a site between two nucleotides, e.g., adjacent nucleotides, on the target nucleic acid into which one or more nucleotides is added. The target position may comprise one or more nucleotides that are altered, e.g., corrected, by a template nucleic acid. In an embodiment, the target position is within a target sequence (e.g., the sequence to which the gRNA binds). In an embodiment, a target position is upstream or downstream of a target sequence (e.g., the sequence to which the gRNA binds).

Typically, the template sequence undergoes a breakage mediated or catalyzed recombination with the target sequence. In an embodiment, the template nucleic acid includes sequence that corresponds to a site on the target sequence that is cleaved by a Cas9 mediated cleavage event. In an embodiment, the template nucleic acid includes sequence that corresponds to both a first site on the target sequence that is cleaved in a first Cas9 mediated event, and a second site on the target sequence that is cleaved in a second Cas9 mediated event.

In an embodiment, the template nucleic acid can include sequence which results in an alteration in the coding sequence of a translated sequence, e.g., one which results in the substitution of one amino acid for another in a protein product, e.g., transforming a mutant allele into a wild type allele, transforming a wild type allele into a mutant allele, and/or introducing a stop codon, insertion of an amino acid residue, deletion of an amino acid residue, or a nonsense mutation.

In other embodiments, the template nucleic acid can include sequence which results in an alteration in a coding sequence, e.g., in an exon, or non-coding sequence, e.g., an alteration in an intron or in a 5′ or 3′ non-translated or non-transcribed region. Such alterations include an alteration in a control element, e.g., a promoter, enhancer, and an alteration in a cis-acting or trans-acting control element. In some embodiments, the alteration includes the insertion of nucleic acid sequence, e.g., nucleic acid sequence encoding a heterologous protein, e.g., a CAR, e.g., as described herein, at or near the target sequence, e.g., the target sequence recognized by a gRNA molecule described herein.

The template nucleic acid can include sequence which, when integrated, results in:

decreasing the activity of a positive control element; increasing the activity of a positive control element; decreasing the activity of a negative control element; increasing the activity of a negative control element; decreasing the expression of a gene; increasing the expression of a gene; increasing resistance to a disorder or disease; increasing resistance to viral entry; correcting a mutation or altering an unwanted amino acid residue conferring, increasing, abolishing or decreasing a biological property of a gene product, e.g., increasing the enzymatic activity of an enzyme, or increasing the ability of a gene product to interact with another molecule.

The template nucleic acid can include sequence which results in:

a change in sequence of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more nucleotides of the target sequence.

In an embodiment, the template nucleic acid is 20+/−10, 30+/−10, 40+/−10, 50+/−10, 60+/−10, 70+/−10, 80+/−10, 90+/−10, 100+/−10, 110+/−10, 120+/−10, 130+/−10, 140+/−10, 150+/−10, 160+/−10, 170+/−10, 180+/−10, 190+/−10, 200+/−10, 210+/−10, 220+/−10, 200-300, 300-400, 400-500, 500-600, 600-700, 700-800, 800-900, 900-1000, 1000-2000, 2000-3000 or more than 3000 nucleotides in length.

A template nucleic acid comprises the following components:

[5′ homology arm]-[insertion sequence]-[3′ homology arm].

The homology arms provide for recombination into the chromosome, which can replace the undesired element, e.g., a mutation or signature, with the replacement sequence, or insert the desired sequence. In an embodiment, the homology arms flank the most distal cleavage sites.

In an embodiment, the 3′ end of the 5′ homology arm is the position next to the 5′ end of the replacement sequence. In an embodiment, the 5′ homology arm can extend at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, 180, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 nucleotides 5′ from the 5′ end of the replacement sequence.

In an embodiment, the 5′ end of the 3′ homology arm is the position next to the 3′ end of the replacement sequence. In an embodiment, the 3′ homology arm can extend at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, 180, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 nucleotides 3′ from the 3′ end of the replacement sequence.

›TGTGAA · 2 of 11

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5′ homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3′ homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5′ and the 3′ homology arms may be shortened to avoid including certain sequence repeat elements.

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single-stranded oligonucleotide (ssODN). When using a ssODN, 5′ and 3′ homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In one aspect, the insertion sequence comprises nucleic acid sequence that encodes a chimeric antigen receptor, e.g., as described herein. In one embodiment the insertion sequence further comprises a promotor operably linked to the nucleic acid sequence encoding a chimeric antigen receptor, e.g., an EF-1 alpha promoter. In one aspect, the insertion sequence comprises a vector encoding a chimeric antigen receptor, e.g., as described herein, or a portion thereof.

NHEJ Approaches for Gene Targeting

As described herein, nuclease-induced non-homologous end-joining (NHEJ) can be used to target gene-specific knockouts. Nuclease-induced NHEJ can also be used to remove (e.g., delete) sequence in a gene of interest.

While not wishing to be bound by theory, it is believed that, in an embodiment, the genomic alterations associated with the methods described herein rely on nuclease-induced NHEJ and the error-prone nature of the NHEJ repair pathway. NHEJ repairs a double-strand break in the DNA by joining together the two ends; however, generally, the original sequence is restored only if two compatible ends, exactly as they were formed by the double-strand break, are perfectly ligated. The DNA ends of the double-strand break are frequently the subject of enzymatic processing, resulting in the addition or removal of nucleotides, at one or both strands, prior to rejoining of the ends. This results in the presence of insertion and/or deletion (indel) mutations in the DNA sequence at the site of the NHEJ repair. Two-thirds of these mutations may alter the reading frame and, therefore, produce a non-functional protein. Additionally, mutations that maintain the reading frame, but which insert or delete a significant amount of sequence, can destroy functionality of the protein. This is locus dependent as mutations in critical functional domains are likely less tolerable than mutations in non-critical regions of the protein.

The indel mutations generated by NHEJ are unpredictable in nature; however, at a given break site certain indel sequences are favored and are over represented in the population. The lengths of deletions can vary widely; most commonly in the 1-50 bp range, but they can easily reach greater than 100-200 bp. Insertions tend to be shorter and often include short duplications of the sequence immediately surrounding the break site. However, it is possible to obtain large insertions, and in these cases, the inserted sequence has often been traced to other regions of the genome or to plasmid DNA present in the cells.

Because NHEJ is a mutagenic process, it can also be used to delete small sequence motifs as long as the generation of a specific final sequence is not required. If a double-strand break is targeted near to a short target sequence, the deletion mutations caused by the NHEJ repair often span, and therefore remove, the unwanted nucleotides. For the deletion of larger DNA segments, introducing two double-strand breaks, one on each side of the sequence, can result in NHEJ between the ends with removal of the entire intervening sequence. Both of these approaches can be used to delete specific DNA sequences; however, the error-prone nature of NHEJ may still produce indel mutations at the site of repair.

Both double strand cleaving Cas9 molecules and single strand, or nickase, Cas9 molecules can be used in the methods and compositions described herein to generate NHEJ-mediated indels. NHEJ-mediated indels targeted to the gene, e.g., a coding region, e.g., an early coding region of a gene of interest can be used to knockout (i.e., eliminate expression of) a gene of interest. For example, early coding region of a gene of interest includes sequence immediately following a transcription start site, within a first exon of the coding sequence, or within 500 bp of the transcription start site (e.g., less than 500, 450, 400, 350, 300, 250, 200, 150, 100 or 50 bp).

Placement of double strand or single strand breaks relative to the target position

In an embodiment, in which a gRNA and Cas9 nuclease generate a double strand break for the purpose of inducing NHEJ-mediated indels, a gRNA, e.g., a unimolecular (or chimeric) or modular gRNA molecule, is configured to position one double-strand break in close proximity to a nucleotide of the target position. In an embodiment, the cleavage site is between 0-500 bp away from the target position (e.g., less than 500, 400, 300, 200, 100, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 bp from the target position).

In an embodiment, in which two gRNAs complexing with Cas9 nickases induce two single strand breaks for the purpose of inducing NHEJ-mediated indels, two gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position two single-strand breaks to provide for NHEJ repair a nucleotide of the target position. In an embodiment, the gRNAs are configured to position cuts at the same position, or within a few nucleotides of one another, on different strands, essentially mimicking a double strand break. In an embodiment, the closer nick is between 0-30 bp away from the target position (e.g., less than 30, 25, 20, 1, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 bp from the target position), and the two nicks are within 25-55 bp of each other (e.g., between 25 to 50, 25 to 45, 25 to 40, 25 to 35, 25 to 30, 50 to 55, 45 to 55, 40 to 55, 35 to 55, 30 to 55, 30 to 50, 35 to 50, 40 to 50, 45 to 50, 35 to 45, or 40 to 45 bp) and no more than 100 bp away from each other (e.g., no more than 90, 80, 70, 60, 50, 40, 30, 20 or 10 bp). In an embodiment, the gRNAs are configured to place a single strand break on either side of a nucleotide of the target position.

›TGTGAA · 3 of 11

Both double strand cleaving Cas9 molecules and single strand, or nickase, Cas9 molecules can be used in the methods and compositions described herein to generate breaks both sides of a target position. Double strand or paired single strand breaks may be generated on both sides of a target position to remove the nucleic acid sequence between the two cuts (e.g., the region between the two breaks is deleted). In one embodiment, two gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position a double-strand break on both sides of a target position (e.g., the first gRNA is used to target upstream (i.e., 5′) of the mutation in a gene or pathway described herein, and the second gRNA is used to target downstream (i.e., 3′) of the mutation in a gene or pathway described herein). In an alternate embodiment, three gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position a double strand break (i.e., one gRNA complexes with a Cas9 nuclease) and two single strand breaks or paired single stranded breaks (i.e., two gRNAs complex with Cas9 nickases) on either side of a target position (e.g., the first gRNA is used to target upstream (i.e., 5′) of the mutation in a gene or pathway described herein, and the second gRNA is used to target downstream (i.e., 3′) of the mutation in a gene or pathway described herein). In another embodiment, four gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to generate two pairs of single stranded breaks (i.e., two pairs of two gRNAs complex with Cas9 nickases) on either side of the target position (e.g., the first gRNA is used to target upstream (i.e., 5′) of the mutation in a gene or pathway described herein, and the second gRNA is used to target downstream (i.e., 3′) of the mutation in a gene or pathway described herein). The double strand break(s) or the closer of the two single strand nicks in a pair will ideally be within 0-500 bp of the target position (e.g., no more than 450, 400, 350, 300, 250, 200, 150, 100, 50 or 25 bp from the target position). When nickases are used, the two nicks in a pair are within 25-55 bp of each other (e.g., between 25 to 50, 25 to 45, 25 to 40, 25 to 35, 25 to 30, 50 to 55, 45 to 55, 40 to 55, 35 to 55, 30 to 55, 30 to 50, 35 to 50, 40 to 50, 45 to 50, 35 to 45, or 40 to 45 bp) and no more than 100 bp away from each other (e.g., no more than 90, 80, 70, 60, 50, 40, 30, 20 or 10 bp).

Thus, in a specific embodiment, the disclosure provides a method of manufacturing a cell, e.g., an immune effector cell, e.g., a T cell, e.g., as described herein, for adoptive immunotherapy, the method comprising:

a) Introducing into said cell 1) a gRNA molecule (e.g., a CRISPR system comprising said gRNA molecule) described herein, e.g., a gRNA molecule to a tet intron or intron-exon junction, e.g., tet2 intron or intron-exon junction, e.g., a gRNA molecule comprising a targeting domain in Table 1 or Table 2 and 2) a template nucleic acid, e.g., a template nucleic acid comprising nucleic acid sequence encoding a CAR (e.g., as described herein);

Wherein at least a portion of the template nucleic acid (e.g., the nucleic acid sequence encoding a CAR) integrates into the genome of said cell within a tet, e.g., tet2 intron (e.g., at or near the target sequence of the tet, e.g., tet2 gRNA molecule).

In some embodiments, the template nucleic acid sequence for targeting a TET2 intron or intron-exon junction comprises a nucleic acid sequence encoding a CAR selected from CD19 CAR, BCMA CAR, and CD22 CAR (e.g., as described herein); the template nucleic acid sequence further comprises a first homology arm comprising SEQ ID NO: 124 and a second homology arm comprising SEQ ID NO: 125; and the gRNA molecule is selected from a gRNA comprising a targeting domain complementary to a sequence within a genomic region (according to hg38) of chr4:105269748-105272563, e.g., chr4:105270624-105270643, chr4:105270630-105270649, chr4:105271863-105271883.

In some embodiments, the template nucleic acid sequence for targeting a TET2 intron or intron-exon junction comprises a first homology arm comprising SEQ ID NO: 124 and a second homology arm comprising SEQ ID NO: 125; and the gRNA molecule is selected from a gRNA comprising a targeting domain complementary to a sequence within a genomic region (according to hg38) of chr4:105269748-105272563, e.g., chr4:105270624-105270643, chr4:105270630-105270649, chr4:105271863-105271883.

In some embodiments, the template nucleic acid sequence for targeting a TET2 intron or intron-exon junction comprises a nucleic acid sequence encoding a CAR selected from CD19 CAR, BCMA CAR, and CD22 CAR (e.g., as described herein); and the gRNA molecule is selected from a gRNA comprising a targeting domain complementary to a sequence within a genomic region (according to hg38) of chr4:105269748-105272563, e.g., chr4:105270624-105270643, chr4:105270630-105270649, chr4:105271863-105271883.

In some embodiments, the template nucleic acid sequence for targeting a TET2 intron or intron-exon junction is provided on an AAV6 vector; the template nucleic acid sequence comprises a nucleic acid sequence encoding a CAR selected from CD19, BCMA, and CD22; the template nucleic acid sequence further comprises a first homology arm comprising SEQ ID NO: 124 and a second homology arm comprising SEQ ID NO: 125; and the gRNA molecule is selected from a gRNA comprising a targeting domain complementary to a sequence within a genomic region (according to hg38) of chr4:105269748-105272563, e.g., chr4:105270624-105270643, chr4:105270630-105270649, chr4:105271863-105271883.

In some embodiments, the template nucleic acid sequence for targeting a TET2 intron or intron-exon junction is provided on an AAV6 vector; the template nucleic acid sequence comprises a first homology arm comprising SEQ ID NO: 124 and a second homology arm comprising SEQ ID NO: 125; and the gRNA molecule is selected from a gRNA comprising a targeting domain complementary to a sequence within a genomic region (according to hg38) of chr4:105269748-105272563, e.g., chr4:105270624-105270643, chr4:105270630-105270649, chr4:105271863-105271883.

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In some embodiments, the template nucleic acid sequence for targeting a TET2 intron or intron-exon junction is provided on an AAV6 vector; the template nucleic acid sequence comprises a nucleic acid sequence encoding a CAR selected from CD19 CAR, BCMA CAR, and CD22 CAR (e.g., as described herein); and the gRNA molecule is selected from a gRNA comprising a targeting domain complementary to a sequence within a genomic region (according to hg38) of chr4:105269748-105272563, e.g., chr4:105270624-105270643, chr4:105270630-105270649, chr4:105271863-105271883.

In some embodiments, the template nucleic acid sequence for targeting a TET2 intron or intron-exon junction is provided on an AAV6 vector; and the gRNA molecule is selected from a gRNA comprising a targeting domain complementary to a sequence within a genomic region (according to hg38) of chr4:105269748-105272563, e.g., chr4:105270624-105270643, chr4:105270630-105270649, chr4:105271863-105271883.

In some embodiments, the template nucleic acid sequence for targeting a TET2 intron or intron-exon junction comprises a nucleic acid sequence encoding a CAR selected from CD19 CAR, BCMA CAR, and CD22 CAR (e.g., as described herein); the template nucleic acid sequence further comprises a first homology arm comprising SEQ ID NO: 124 and a second homology arm comprising SEQ ID NO: 125; and the gRNA molecule is selected from a gRNA comprising a targeting domain of any of the sequences in Table 1 or Table 2, e.g., SEQ ID NO: 10148, SEQ ID NO: 10149, SEQ ID NO: 10206, e.g., SEQ ID NO: 10148 or SEQ ID NO: 10149.

In some embodiments, the template nucleic acid sequence for targeting a TET2 intron or intron-exon junction comprises a first homology arm comprising SEQ ID NO: 124 and a second homology arm comprising SEQ ID NO: 125; and the gRNA molecule is selected from a gRNA comprising a targeting domain of any of the sequences in Table 1 or Table 2, e.g., SEQ ID NO: 10148, SEQ ID NO: 10149, SEQ ID NO: 10206.

In some embodiments, the template nucleic acid sequence for targeting a TET2 intron or intron-exon junction comprises a nucleic acid sequence encoding a CAR selected from CD19 CAR, BCMA CAR, and CD22 CAR (e.g., as described herein); and the gRNA molecule is selected from a gRNA comprising a targeting domain of any of the sequences in Table 1 or Table 2.

In some embodiments, the template nucleic acid sequence for targeting a TET2 intron or intron-exon junction is provided on an AAV6 vector; the template nucleic acid sequence comprises a nucleic acid sequence encoding a CAR selected from CD19, BCMA, and CD22; the template nucleic acid sequence further comprises a first homology arm comprising SEQ ID NO: 124 and a second homology arm comprising SEQ ID NO: 125; and the gRNA molecule is selected from a gRNA comprising a targeting domain of any of the sequences in Table 1 or Table 2, e.g., SEQ ID NO: 10148, SEQ ID NO: 10149, SEQ ID NO: 10206.

In some embodiments, the template nucleic acid sequence for targeting a TET2 intron or intron-exon junction is provided on an AAV6 vector; the template nucleic acid sequence comprises a first homology arm comprising SEQ ID NO: 124 and a second homology arm comprising SEQ ID NO: 125; and the gRNA molecule is selected from a gRNA comprising a targeting domain of any of the sequences in Table 1 or Table 2, e.g., SEQ ID NO: 10148, SEQ ID NO: 10149, SEQ ID NO: 10206.

In some embodiments, the template nucleic acid sequence for targeting a TET2 intron or intron-exon junction is provided on an AAV6 vector; the template nucleic acid sequence comprises a nucleic acid sequence encoding a CAR selected from CD19 CAR, BCMA CAR, and CD22 CAR (e.g., as described herein); and the gRNA molecule is selected from a gRNA comprising a targeting domain of any of the sequences in Table 1 or Table 2, e.g., SEQ ID NO: 10148, SEQ ID NO: 10149, SEQ ID NO: 10206.

In some embodiments, the template nucleic acid sequence for targeting a TET2 intron or intron-exon junction is provided on an AAV6 vector; and the gRNA molecule is selected from a gRNA comprising a targeting domain of any of the sequences in Table 1 or Table 2, e.g., SEQ ID NO: 10148, SEQ ID NO: 10149, SEQ ID NO: 10206.

In some embodiments, the template nucleic acid comprises SEQ ID NO: 126. In some embodiments, the template nucleic acid comprises SEQ ID NO: 126 and is provided on an AAV vector, e.g., an AAV6 vector. In some embodiments, the template nucleic acid comprises SEQ ID NO: 126 and is provided on an AAV vector, e.g., an AAV6 vector, and the gRNA molecule is selected from a gRNA comprising a targeting domain of any of the sequences in Table 1 or Table 2, e.g., SEQ ID NO: 10148, SEQ ID NO: 10149, SEQ ID NO: 10206, e.g., selected from SEQ ID NO: 10148 and SEQ ID NO: 10149.

In some embodiments, a gRNA molecule described herein and a Cas9 molecule described herein are mixed to form a ribonuclear protein complex (RNP); next the RNP is introduced to a cell described herein; and then the cell is introduced to the vector described herein, e.g., AAV6.

In some embodiments, the gRNA molecules disclosed herein are capable of generating the editing repair pattern described in Table 22 and/or the indel frequencies described in Table 23.

The disclosure also provides cells that comprise or at one time comprised one or more gRNA molecules disclosed herein, and exhibit or at one time exhibited the editing repair pattern described in Table 22 and/or the indel frequencies described in Table 23.

VIII. Systems Comprising More Than One gRNA Molecule

While not intending to be bound by theory, targeting of two target sequences (e.g., by two gRNA molecule/Cas9 molecule complexes which each induce a single- or double-strand break at or near their respective target sequences) located in close proximity on a continuous nucleic acid induces excision (e.g., deletion) of the nucleic acid sequence (or at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% of the nucleic acid sequence) located between the two target sequences. In some aspects, the present disclosure provides for the use of two or more gRNA molecules that comprise targeting domains targeting target sequences in close proximity on a continuous nucleic acid, e.g., a chromosome, e.g., a gene or gene locus, including its introns, exons and regulatory elements. The use may be, for example, by introduction of the two or more gRNA molecules, together with one or more Cas9 molecules (or nucleic acid encoding the two or more gRNA molecules and/or the one or more Cas9 molecules) into a cell. Such systems may be used, for example, to insert heterologous nucleic acid sequence, e.g., sequence from a template nucleic acid, e.g., sequence encoding a CAR (e.g., as described herein) into the site of the excision.

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In some aspects, the target sequences of the two or more gRNA molecules are located at least 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 2000, 3000, 4000, 5000, 6000, or 70000 nucleotides apart on a continuous nucleic acid, but not more than 10000 nucleotides apart on a continuous nucleic acid. In an embodiment, the target sequences are located about 4000 nucleotides apart. In an embodiment, the target sequences are located about 6000 nucleotides apart.

In some aspects, the plurality of gRNA molecules each target sequences within the same gene or gene locus. In another aspect, the plurality of gRNA molecules each target sequences within 2 or more different genes.

In some aspects, the disclosure provides compositions and cells comprising a plurality, for example, 2 or more, for example, 2, gRNA molecules of the disclosure, wherein the plurality of gRNA molecules target sequences less than 10,000, less than 9,000, less than 8,000, less than 7,000, less than 6,000, less than 5,000, less than 4,000, less than 3,000, less than 2,000, less than 1,000, less than 900, less than 800, less than 700, less than 600, less than 500, less than 400, less than 300, less than 200, less than 100, less than 90, less than 80, less than 70, less than 60, less than 50, less than 40, or less than 30 nucleotides apart. In an embodiment, the target sequences are on the same strand of duplex nucleic acid. In an embodiment, the target sequences are on different strands of duplex nucleic acid.

In one embodiment, the disclosure provides a method for excising (e.g., deleting) nucleic acid disposed between two gRNA binding sites disposed less than 10,000, less than 9,000, less than 8,000, less than 7,000, less than 6,000, less than 5,000, less than 4,000, less than 3,000, less than 2,000, less than 1,000, less than 900, less than 800, less than 700, less than 600, less than 500, less than 400, less than 300, less than 200, less than 100, less than 90, less than 80, less than 70, less than 60, less than 50, less than 40, or less than 30 nucleotides apart on the same or different strands of duplex nucleic acid. In an embodiment, the method provides for deletion of more than 50%, more than 60%, more than 70%, more than 80%, more than 85%, more than 86%, more than 87%, more than 88%, more than 89%, more than 90%, more than 91%, more than 92%, more than 93%, more than 94%, more than 95%, more than 96%, more than 97%, more than 98%, more than 99%, or 100% of the nucleotides disposed between the PAM sites associated with each gRNA binding site. In embodiments, the deletion further comprises of one or more nucleotides within one or more of the PAM sites associated with each gRNA binding site. In embodiments, the deletion also comprises one or more nucleotides outside of the region between the PAM sites associated with each gRNA binding site.

In one aspect, the two or more gRNA molecules comprise targeting domains targeting target sequences flanking a gene regulatory element, e.g., a promotor binding site, an enhancer region, or a repressor region, such that excision of the intervening sequence (or a portion of the intervening sequence) causes up- or down-regulation of a gene of interest.

In an embodiment, the two or more gRNA molecules are selected from the gRNA molecules of Table 1 or Table 2. In aspects, the two or more gRNA molecules comprise targeting domains that are complementary with sequences in the same gene, for example, same region, e.g., same intron.

In addition to the gRNA molecules described herein, e.g., gRNA molecules to a tet intron or intron-exon junction, e.g., tet2 intron or intron-exon junction, the CRISPR systems, cells, methods and other embodiments of the disclosure may further include one or more additional gRNA molecules, CRISPR systems or, in the case of, for example, cells, one or more alterations within other genes, for example, effected by CRISPR systems.

As described herein, when utilizing more than one gRNA molecule (or CRISPR system comprising more than one gRNA molecule, e.g., a CRISPR system comprising a first gRNA molecule and a CRISPR system comprising a second gRNA molecule, e.g., wherein each gRNA molecule is complexed with a Cas molecule, e.g., a Cas9 molecule, e.g., as described herein), the more than one gRNA molecules may be introduced into a cell simultaneously, e.g., in a single introduction step, e.g., a single electroporation step. Alternatively, the more than one gRNA molecules (or CRISPR systems comprising said gRNA molecules) can be introduced into a cell in more than one steps, e.g., more than one electroporations. If multiple introduction steps are utilized, the steps may be separated by a period of hours, days, or weeks, e.g., by a period of 1 hour, 2 hours, 5 hours, 10 hours, 15 hours, 20 hours, 24 hours, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, or more.

In embodiments where template nucleic acid is utilized and it is desired to insert nucleic acid sequence only at a target sequence of one of the gRNA molecules in a system or method utilizing more than one gRNA molecule, the alteration of the cell of interest can be accomplished in stepwise fashion. For example, in a first step, a CRISPR system comprising a gRNA molecule which binds the target sequence where insertion is desired is introduced into the cell together with a template nucleic acid, e.g., as described herein. In a second step, for example, at a time when there is no longer template nucleic acid present in said cell, one or more CRISPR systems comprising one or more gRNA molecules to additional target sequences (e.g., target sequences in genes where it is desired to have reduced or eliminated function or expression of said gene or genes) are introduced. In embodiments, the first and second steps may be reversed in order. In embodiments, the second step may comprise a plurality of steps, each involving a single CRISPR system/gRNA molecule.

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In a specific embodiment, the disclosure provides a method of manufacturing a cell, e.g., an immune effector cell, e.g., a T cell, e.g., as described herein, for adoptive immunotherapy, the method comprising:

a) Introducing into said cell 1) a gRNA molecule (e.g., a CRISPR system comprising said gRNA molecule) described herein, e.g., a gRNA molecule to a tet intron or intron-exon junction, e.g., tet2 intron or intron-exon junction, e.g., a gRNA molecule comprising a targeting domain in Table 1 or Table 2 and 2) a template nucleic acid, e.g., a template nucleic acid comprising nucleic acid sequence encoding a CAR (e.g., as described herein); and b) Introducing into said cell a gRNA molecule (e.g., a CRISPR system comprising said gRNA molecule) comprising a targeting domain specific for a target sequence of a component of the T cell receptor (e.g., TRAC, TRBC, CD3E, CD3D, or CD3G), and/or introducing into said cell a gRNA molecule (e.g., a CRISPR system comprising said gRNA molecule) comprising a targeting domain specific for a target sequence of B2M and/or Introducing into said cell a gRNA molecule (e.g., a CRISPR system comprising said gRNA molecule) comprising a targeting domain specific for a target sequence of CIITA;

Wherein at least a portion of the template nucleic acid (e.g., the nucleic acid sequence encoding a CAR) integrates into the genome of said cell within a tet, e.g., tet2 intron (e.g., at or near the target sequence of the tet, e.g., tet2 gRNA molecule) and said cell has reduced or eliminated expression of a component of the T cell, B2M and/or CIITA.

In a specific embodiment, the disclosure provides a method of manufacturing a cell, e.g., an immune effector cell, e.g., a T cell, e.g., as described herein, for adoptive immunotherapy, the method comprising:

a) Introducing into said cell 1) a gRNA molecule (e.g., a CRISPR system comprising said gRNA molecule) described herein, e.g., a gRNA molecule to a tet intron or intron-exon junction, e.g., tet2 intron or intron-exon junction, e.g., a gRNA molecule comprising a targeting domain in Table 1 or Table 2 and 2) a template nucleic acid, e.g., a template nucleic acid comprising nucleic acid sequence encoding a CAR (e.g., as described herein); and b) Introducing into said cell a gRNA molecule (e.g., a CRISPR system comprising said gRNA molecule) comprising a targeting domain specific for a target sequence of a component of the T cell receptor (e.g., TRAC, TRBC, CD3E, CD3D, or CD3G), and/or introducing into said cell a gRNA molecule (e.g., a CRISPR system comprising said gRNA molecule) comprising a targeting domain specific for a target of an immunosuppressant;

Wherein at least a portion of the template nucleic acid (e.g., the nucleic acid sequence encoding a CAR) integrates into the genome of said cell within a tet, e.g., tet2 intron (e.g., at or near the target sequence of the tet, e.g., tet2 gRNA molecule) and said cell has reduced or eliminated expression of a target for an immunosuppressant. Exemplary targets of an immunosuppressant include FKBP1A or CD52.

IX. Properties of the gRNA

While not intending to be bound by theory, gRNA molecules and CRISPR systems comprising said gRNA molecules produce similar or identical indel patterns when the same system is used in the same cell type through multiple experiments. Without being bound by theory, it is believed that some indel patterns may be more advantageous than others. For example, indels which predominantly include insertions and/or deletions which result in a “frameshift mutation” (e.g., 1- or 2-base pair insertion or deletions, or any insertion or deletion where n/3 is not a whole number (where n=the number of nucleotides in the insertion or deletion)) may be beneficial in reducing or eliminating expression of a functional protein. Likewise, indels which predominantly include “large deletions” (deletions of more than 10, 11, 12, 13, 14, 15, 20, 25, or 30 nucleotides) may also be beneficial in, for example, removing critical regulatory sequences such as promoter binding sites, which may similarly have an improved effect on expression of functional protein. While the indel patterns induced by a given gRNA/CRISPR system have surprisingly been found to be consistently reproduced across cell types, as described herein, not any single indel structure will inevitably be produced in a given cell upon introduction of a gRNA/CRISPR system. In embodiments, specific gRNAs, Cas molecules, cell types, scaffolds, etc., may be selected to affect the indel patterns induced by the CRISPR system.

The disclosure thus provides for gRNA molecules which create a beneficial indel pattern or structure, for example, which have indel patterns or structures predominantly composed of frameshift mutation(s) and/or large deletions. Such gRNA molecules may be selected by assessing the indel pattern or structure created by a candidate gRNA molecule in a test cell (for example, a HEK293 cell or in the cell of interest, e.g., a T cell) by NGS, as described herein. As shown in the Examples, gRNA molecules have been discovered, which, when introduced into the desired cell population, result in a population of cells comprising a significant fraction of the cells having a frameshift mutation in the targeted gene. In some cases, the rate of frameshift mutation is as high as 75%, 80%, 85%, 90% or more. The disclosure thus provides for populations of cells which comprise at least about 40% of cells (e.g., at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99%) having a frameshift mutation, e.g., as described herein, at or near the target site of a gRNA molecule described herein. The disclosure also provides for populations of cells which comprise at least about 50% of cells (e.g., at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99%) having a frameshift mutation, e.g., as described herein, at or near the target site of a gRNA molecule described herein.

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The disclosure thus provides methods of selecting gRNA molecules for use in the therapeutic methods of the disclosure comprising: 1) providing a plurality of gRNA molecules to a target of interest, 2) assessing the indel pattern or structure created by use of said gRNA molecules, 3) selecting a gRNA molecule that forms an indel pattern or structure composed predominantly of frameshift mutations, large deletions or a combination thereof, and 4) using said selected gRNA in a methods of the disclosure.

The disclosure further provides methods of altering cells, and altered cells, wherein a particular indel pattern is consistently produced with a given gRNA/CRISPR system in that cell type.

It may also be beneficial to utilize gRNA molecules that do not create indels at off-target sequences within the genome of the target cell type, or produce indels at off target sites at very low frequencies (e.g., <5% of cells within a population) relative to the frequency of indel creation at the target site. Thus, the disclosure provides for gRNA molecules and CRISPR systems which do not exhibit off-target indel formation in the target cell type, or which produce a frequency of off-target indel formation of <5%. In embodiments, the disclosure provides gRNA molecules and CRISPR systems which do not exhibit any off target indel formation in the target cell type. Thus, the disclosure further provides a cell, e.g., a population of cells, e.g., immune effector cells, e.g., CAR-expressing immune effector cells, e.g., as described herein, which comprise an indel at or near a target site of a gRNA molecule described herein (e.g., a frameshift indel, or any one of the top 5 indels produced by a given gRNA/CRISPR system, e.g., as described herein), but does not comprise an indel at any off-target site of the gRNA molecule. In other embodiments, the disclosure further provides a population of cells, e.g., immune effector cells, e.g., CAR-expressing immune effector cells, e.g., as described herein, which comprises >50% of cells which have an indel at or near a target site of a gRNA molecule described herein (e.g., a frameshift indel, or any one of the top 5 indels produced by a given gRNA/CRISPR system, e.g., as described herein), but which comprises less than 5%, e.g., less than 4%, less than 3%, less than 2% or less than 1%, of cells comprising an indel at any off-target site of the gRNA molecule.

X. Delivery/Constructs

The components, e.g., a Cas9 molecule, gRNA molecule and/or template nucleic acid, or combinations thereof, can be delivered, formulated, or administered in a variety of forms. As a non-limiting example, the gRNA molecule and Cas9 molecule can be formulated (in one or more compositions), directly delivered or administered to a cell in which a genome editing event is desired. Alternatively, nucleic acid encoding one or more components, e.g., a Cas9 molecule or gRNA molecule, or both, can be formulated (in one or more compositions), delivered or administered. In one aspect, the gRNA molecule is provided as DNA encoding the gRNA molecule and the Cas9 molecule is provided as DNA encoding the Cas9 molecule. In one embodiment, the gRNA molecule and Cas9 molecule are encoded on separate nucleic acid molecules. In one embodiment, the gRNA molecule and Cas9 molecule are encoded on the same nucleic acid molecule. In one aspect, the gRNA molecule is provided as RNA and the Cas9 molecule is provided as DNA encoding the Cas9 molecule. In one embodiment, the gRNA molecule is provided with one or more modifications, e.g., as described herein. In one aspect, the gRNA molecule is provided as RNA and the Cas9 molecule is provided as mRNA encoding the Cas9 molecule. In one aspect, the gRNA molecule is provided as RNA and the Cas9 molecule is provided as a protein. In one embodiment, the gRNA and Cas9 molecule are provided as a ribonuclear protein complex (RNP). In one aspect, the gRNA molecule is provided as DNA encoding the gRNA molecule and the Cas9 molecule is provided as a protein. In any of the aforementioned embodiments, the composition may further include a template nucleic acid.

Delivery may be accomplished by, for example, electroporation (e.g., as known in the art) or other method that renders the cell membrane permeable to nucleic acid and/or polypeptide molecules. Additional techniques for rendering the membrane permeable are known in the art and include, for example, cell squeezing (e.g., as described in WO2015/023982 and WO2013/059343, the contents of which are hereby incorporated by reference in their entirety), nanoneedles (e.g., as described in Chiappini et al., Nat. Mat., 14; 532-39, or US2014/0295558, the contents of which are hereby incorporated by reference in their entirety) and nanostraws (e.g., as described in Xie, ACS Nano, 7(5); 4351-58, the contents of which are hereby incorporated by reference in their entirety).

When a component is delivered encoded in DNA the DNA will typically include a control region, e.g., comprising a promoter, to effect expression. Useful promoters for Cas9 molecule sequences include CMV, EF-1alpha, MSCV, PGK, CAG control promoters. Useful promoters for gRNAs include H1, EF-1a and U6 promoters. Promoters with similar or dissimilar strengths can be selected to tune the expression of components. Sequences encoding a Cas9 molecule can comprise a nuclear localization signal (NLS), e.g., an SV40 NLS. In an embodiment, a promoter for a Cas9 molecule or a gRNA molecule can be, independently, inducible, tissue specific, or cell specific.

DNA-Based Delivery of a Cas9 Molecule and or a gRNA Molecule

DNA encoding Cas9 molecules and/or gRNA molecules, can be administered to subjects or delivered into cells by art-known methods or as described herein. For example, Cas9-encoding and/or gRNA-encoding DNA can be delivered, e.g., by vectors (e.g., viral or non-viral vectors), non-vector based methods (e.g., using naked DNA or DNA complexes), or a combination thereof.

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a vector (e.g., viral vector/virus, plasmid, minicircle or nanoplasmid). In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by at least one vector. For example, the Cas9 is delivered by a vector that is different than the vector by which the gRNA-encoding DNA is delivered.

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A vector can comprise a sequence that encodes a Cas9 molecule and/or a gRNA molecule. A vector can also comprise a sequence encoding a signal peptide (e.g., for nuclear localization, nucleolar localization, mitochondrial localization), fused, e.g., to a Cas9 molecule sequence. For example, a vector can comprise one or more nuclear localization sequence (e.g., from SV40) fused to the sequence encoding the Cas9 molecule.

One or more regulatory/control elements, e.g., a promoter, an enhancer, an intron, a polyadenylation signal, a Kozak consensus sequence, internal ribosome entry sites (IRES), a 2A sequence, and a splice acceptor or donor can be included in the vectors. In some embodiments, the promoter is recognized by RNA polymerase II (e.g., a CMV promoter). In other embodiments, the promoter is recognized by RNA polymerase III (e.g., a U6 promoter). In some embodiments, the promoter is a regulated promoter (e.g., inducible promoter). In other embodiments, the promoter is a constitutive promoter. In some embodiments, the promoter is a tissue specific promoter. In some embodiments, the promoter is a viral promoter. In other embodiments, the promoter is a non-viral promoter.

In some embodiments, the vector or delivery vehicle is a minicircle. In some embodiments, the vector or delivery vehicle is a nanoplasmid.

In some embodiments, the vector or delivery vehicle is a viral vector (e.g., for generation of recombinant viruses). In some embodiments, the virus is a DNA virus (e.g., dsDNA or ssDNA virus). In other embodiments, the virus is an RNA virus (e.g., an ssRNA virus).

Exemplary viral vectors/viruses include, e.g., retroviruses, lentiviruses, adenovirus, adeno-associated virus (AAV), vaccinia viruses, poxviruses, and herpes simplex viruses. Viral vector technology is well known in the art and is described, for example, in Sambrook et al., 2012, MOLECULAR CLONING: A LABORATORY MANUAL, volumes 1-4, Cold Spring Harbor Press, NY), and in other virology and molecular biology manuals.

In some embodiments, the virus infects dividing cells. In other embodiments, the virus infects non-dividing cells. In some embodiments, the virus infects both dividing and non-dividing cells. In some embodiments, the virus can integrate into the host genome. In some embodiments, the virus is engineered to have reduced immunity, e.g., in human. In some embodiments, the virus is replication-competent. In other embodiments, the virus is replication-defective, e.g., having one or more coding regions for the genes necessary for additional rounds of virion replication and/or packaging replaced with other genes or deleted. In some embodiments, the virus causes transient expression of the Cas9 molecule and/or the gRNA molecule. In other embodiments, the virus causes long-lasting, e.g., at least 1 week, 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 1 year, 2 years, or permanent expression, of the Cas9 molecule and/or the gRNA molecule. The packaging capacity of the viruses may vary, e.g., from at least about 4 kb to at least about 30 kb, e.g., at least about 5 kb, 10 kb, 15 kb, 20 kb, 25 kb, 30 kb, 35 kb, 40 kb, 45 kb, or 50 kb.

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a recombinant retrovirus. In some embodiments, the retrovirus (e.g., Moloney murine leukemia vims) comprises a reverse transcriptase, e.g., that allows integration into the host genome. In some embodiments, the retrovirus is replication-competent. In other embodiments, the retrovirus is replication-defective, e.g., having one of more coding regions for the genes necessary for additional rounds of virion replication and packaging replaced with other genes, or deleted.

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a recombinant lentivirus. For example, the lentivirus is replication-defective, e.g., does not comprise one or more genes required for viral replication.

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a recombinant adenovirus. In some embodiments, the adenovirus is engineered to have reduced immunity in human.

In some embodiments, the Cas9- and/or gRNA-encoding DNA and/or template nucleic acid is delivered by a recombinant AAV. In some embodiments, the AAV can incorporate its genome into that of a host cell, e.g., a target cell as described herein. In some embodiments, the AAV is a self-complementary adeno-associated virus (scAAV), e.g., a scAAV that packages both strands which anneal together to form double stranded DNA. AAV serotypes that may be used in the disclosed methods include, e.g., AAV1, AAV2, modified AAV2 (e.g., modifications at Y444F, Y500F, Y730F and/or S662V), AAV3, modified AAV3 (e.g., modifications at Y705F, Y731F and/or T492V), AAV4, AAV5, AAV6, modified AAV6 (e.g., modifications at S663V and/or T492V), AAV8, AAV8.2, AAV9, AAVrh10, and pseudotyped AAV, such as AAV2/8, AAV2/5 and AAV2/6 can also be used in the disclosed methods. In some embodiments, the recombinant AAV is AAV6.

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a hybrid virus, e.g., a hybrid of one or more of the viruses described herein.

A packaging cell is used to form a virus particle that is capable of infecting a host or target cell. Such a cell includes a 293 cell, which can package adenovirus, and a ω2 cell or a PA317 cell, which can package retrovirus. A viral vector used in gene therapy is usually generated by a producer cell line that packages a nucleic acid vector into a viral particle. The vector typically contains the minimal viral sequences required for packaging and subsequent integration into a host or target cell (if applicable), with other viral sequences being replaced by an expression cassette encoding the protein to be expressed. For example, an AAV vector used in gene therapy typically only possesses inverted terminal repeat (ITR) sequences from the AAV genome which are required for packaging and gene expression in the host or target cell. The missing viral functions are supplied in trans by the packaging cell line. Henceforth, the viral DNA is packaged in a cell line, which contains a helper plasmid encoding the other AAV genes, namely rep and cap, but lacking ITR sequences. The cell line is also infected with adenovirus as a helper. The helper virus promotes replication of the AAV vector and expression of AAV genes from the helper plasmid. The helper plasmid is not packaged in significant amounts due to a lack of ITR sequences. Contamination with adenovirus can be reduced by, e.g., heat treatment to which adenovirus is more sensitive than AAV.

›TGTGAA · 9 of 11

In an embodiment, the viral vector has the ability of cell type and/or tissue type recognition. For example, the viral vector can be pseudotyped with a different/alternative viral envelope glycoprotein; engineered with a cell type-specific receptor (e.g., genetic modification of the viral envelope glycoproteins to incorporate targeting ligands such as a peptide ligand, a single chain antibody, a growth factor); and/or engineered to have a molecular bridge with dual specificities with one end recognizing a viral glycoprotein and the other end recognizing a moiety of the target cell surface (e.g., ligand-receptor, monoclonal antibody, avidin-biotin and chemical conjugation).

In an embodiment, the viral vector achieves cell type specific expression. For example, a tissue-specific promoter can be constructed to restrict expression of the transgene (Cas9 and gRNA) in only the target cell. The specificity of the vector can also be mediated by microRNA-dependent control of transgene expression. In an embodiment, the viral vector has increased efficiency of fusion of the viral vector and a target cell membrane. For example, a fusion protein such as fusion-competent hemagglutin (HA) can be incorporated to increase viral uptake into cells. In an embodiment, the viral vector has the ability of nuclear localization. For example, a virus that requires the breakdown of the cell wall (during cell division) and therefore will not infect a non-diving cell can be altered to incorporate a nuclear localization peptide in the matrix protein of the virus thereby enabling the transduction of non-proliferating cells.

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a non-vector based method (e.g., using naked DNA or DNA complexes). For example, the DNA can be delivered, e.g., by organically modified silica or silicate (Ormosil), electroporation, gene gun, sonoporation, magnetofection, lipid-mediated transfection, dendrimers, inorganic nanoparticles, calcium phosphates, or a combination thereof.

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a combination of a vector and a non-vector based method. For example, a virosome comprises a liposome combined with an inactivated virus (e.g., HIV or influenza virus), which can result in more efficient gene transfer, e.g., in a respiratory epithelial cell than either a viral or a liposomal method alone.

In an embodiment, the delivery vehicle is a non-viral vector. In an embodiment, the non-viral vector is an inorganic nanoparticle (e.g., attached to the payload to the surface of the nanoparticle). Exemplary inorganic nanoparticles include, e.g., magnetic nanoparticles (e.g., Fe lvln0 2 ), or silica. The outer surface of the nanoparticle can be conjugated with a positively charged polymer (e.g., polyethylenimine, polylysine, polyserine) which allows for attachment (e.g., conjugation or entrapment) of payload. In an embodiment, the non-viral vector is an organic nanoparticle (e.g., entrapment of the payload inside the nanoparticle). Exemplary organic nanoparticles include, e.g., SNALP liposomes that contain cationic lipids together with neutral helper lipids which are coated with polyethylene glycol (PEG) and protamine and nucleic acid complex coated with lipid coating.

Exemplary lipids and/or polymers for transfer of CRISPR systems or nucleic acid, e.g., vectors, encoding CRISPR systems or components thereof include, for example, those described in WO2011/076807, WO2014/136086, WO2005/060697, WO2014/140211, WO2012/031046, WO2013/103467, WO2013/006825, WO2012/006378, WO2015/095340, and WO2015/095346, the contents of each of the foregoing are hereby incorporated by reference in their entirety. In an embodiment, the vehicle has targeting modifications to increase target cell update of nanoparticles and liposomes, e.g., cell specific antigens, monoclonal antibodies, single chain antibodies, aptamers, polymers, sugars, and cell penetrating peptides. In an embodiment, the vehicle uses fusogenic and endosome-destabilizing peptides/polymers. In an embodiment, the vehicle undergoes acid-triggered conformational changes (e.g., to accelerate endosomal escape of the cargo). In an embodiment, a stimuli-cleavable polymer is used, e.g., for release in a cellular compartment. For example, disulfide-based cationic polymers that are cleaved in the reducing cellular environment can be used.

In an embodiment, the delivery vehicle is a biological non-viral delivery vehicle. In an embodiment, the vehicle is an attenuated bacterium (e.g., naturally or artificially engineered to be invasive but attenuated to prevent pathogenesis and expressing the transgene (e.g., Listeria monocytogenes , certain Salmonella strains, Bifidobacterium longum , and modified Escherichia coli ), bacteria having nutritional and tissue-specific tropism to target specific tissues, bacteria having modified surface proteins to alter target tissue specificity). In an embodiment, the vehicle is a genetically modified bacteriophage (e.g., engineered phages having large packaging capacity, less immunogenic, containing mammalian plasmid maintenance sequences and having incorporated targeting ligands). In an embodiment, the vehicle is a mammalian virus-like particle. For example, modified viral particles can be generated (e.g., by purification of the “empty” particles followed by ex vivo assembly of the virus with the desired cargo). The vehicle can also be engineered to incorporate targeting ligands to alter target tissue specificity. In an embodiment, the vehicle is a biological liposome. For example, the biological liposome is a phospholipid-based particle derived from human cells (e.g., erythrocyte ghosts, which are red blood cells broken down into spherical structures derived from the subject (e.g., tissue targeting can be achieved by attachment of various tissue or cell-specific ligands), or secretory exosomes—subject (i.e., patient) derived membrane-bound nanovesicle (30-100 nm) of endocytic origin (e.g., can be produced from various cell types and can therefore be taken up by cells without the need of for targeting ligands).

›TGTGAA · 10 of 11

In an embodiment, one or more nucleic acid molecules (e.g., DNA molecules) other than the components of a Cas system, e.g., the Cas9 molecule component and/or the gRNA molecule component described herein, are delivered. In an embodiment, the nucleic acid molecule is delivered at the same time as one or more of the components of the Cas system are delivered. In an embodiment, the nucleic acid molecule is delivered before or after (e.g., less than about 30 minutes, 1 hour, 2 hours, 3 hours, 6 hours, 9 hours, 12 hours, 1 day, 2 days, 3 days, 1 week, 2 weeks, or 4 weeks) one or more of the components of the Cas9 system are delivered. In an embodiment, the nucleic acid molecule is delivered by a different means than one or more of the components of the Cas9 system, e.g., the Cas9 molecule component and/or the gRNA molecule component, are delivered. The nucleic acid molecule can be delivered by any of the delivery methods described herein. For example, the nucleic acid molecule can be delivered by a viral vector, e.g., an integration-deficient lentivirus, and the Cas9 molecule component and/or the gRNA molecule component can be delivered by electroporation, e.g., such that the toxicity caused by nucleic acids (e.g., DNAs) can be reduced. In an embodiment, the nucleic acid molecule encodes a therapeutic protein, e.g., a protein described herein. In an embodiment, the nucleic acid molecule encodes an RNA molecule, e.g., an RNA molecule described herein. Delivery of RNA encoding a Cas9 molecule

RNA encoding Cas9 molecules (e.g., active Cas9 molecules, inactive Cas9 molecules or inactive Cas9 fusion proteins) and/or gRNA molecules, can be delivered into cells, e.g., target cells described herein, by art-known methods or as described herein. For example, Cas9-encoding and/or gRNA-encoding RNA can be delivered, e.g., by microinjection, electroporation, lipid-mediated transfection, peptide-mediated delivery, or a combination thereof.

Delivery of Cas9 Molecule as Protein

Cas9 molecules (e.g., active Cas9 molecules, inactive Cas9 molecules or inactive Cas9 fusion proteins) can be delivered into cells by art-known methods or as described herein. For example, Cas9 protein molecules can be delivered, e.g., by microinjection, electroporation, lipid-mediated transfection, peptide-mediated delivery, cell squeezing or abrasion (e.g., by nanoneedles) or a combination thereof. Delivery can be accompanied by DNA encoding a gRNA or by a gRNA.

In an embodiment the Cas9 molecule, e.g., as described herein, is delivered as a protein and the gRNA molecule is delivered at one or more RNAs (e.g., as a dgRNA or sgRNA, as described herein). In embodiments, the Cas9 protein is complexed with the gRNA molecule prior to delivery to a cell, e.g., as described herein, as a ribonuclear protein complex (“RNP”). In embodiments, the RNP can be delivered into cells, e.g., described herein, by any art-known method, e.g., electroporation. As described herein, and without being bound by theory, it can be preferable to use a gRNA molecule and Cas9 molecule which result in high % editing at the target sequence (e.g., >85%, >90%, >95%, >98%, or >99%) in the target cell, e.g., described herein, even when the concentration of RNP delivered to the cell is reduced. Again, without being bound by theory, delivering a reduced or low concentration of RNP comprising a gRNA molecule that produces a high % editing at the target sequence in the target cell (including at the low RNP concentration), can be beneficial because it may reduce the frequency and number of off-target editing events. In one aspect, where a low or reduced concentration of RNP is to be used, the following procedure can be used to generate the RNP:

1. Provide the Cas9 molecule and the tracr in solution at a high concentration (e.g., a concentration higher than the final RNP concentration to be delivered to the cell), and allow the two components to equilibrate; 2. Provide the crRNA molecule, and allow the components to equilibrate (thereby forming a high-concentration solution of the RNP); 3. Dilute the RNP solution to the desired concentration; 4. Deliver said RNP at said desired concentration to the target cells, e.g., by electroporation.

The above procedure may be modified for use with sgRNA molecules by omitting step 2, above, and in step 1, providing the Cas9 molecule and the sgRNA molecule in solution at high concentration, and allowing the components to equilibrate. In embodiments, the Cas9 molecule and each gRNA component are provided in solution at a 1:2 ratio (Cas9:gRNA), e.g., a 1:2 molar ratio of Cas9:gRNA molecule. Where dgRNA molecules are used, the ratio, e.g., molar ratio, is 1:2:2 (Cas9:tracr:crRNA). In embodiments, the RNP is formed at a concentration of 20 uM or higher, e.g., a concentration from about 20 uM to about 50 uM. In embodiments, the RNP is formed at a concentration of 10 uM or higher, e.g., a concentration from about 10 uM to about 30 uM. In embodiments, the RNP is diluted to a final concentration of 10 uM or less (e.g., a concentration from about 0.01 uM to about 10 uM) in a solution comprising the target cell (e.g., described herein) for delivery to said target cell. In embodiments, the RNP is diluted to a final concentration of 3 uM or less (e.g., a concentration from about 0.01 uM to about 3 uM) in a solution comprising the target cell (e.g., described herein) for delivery to said target cell. In embodiments, the RNP is diluted to a final concentration of 1 uM or less (e.g., a concentration from about 0.01 uM to about 1 uM) in a solution comprising the target cell (e.g., described herein) for delivery to said target cell. In embodiments, the RNP is diluted to a final concentration of 0.3 uM or less (e.g., a concentration from about 0.01 uM to about 0.3 uM) in a solution comprising the target cell (e.g., described herein) for delivery to said target cell. In embodiments, the RNP is provided at a final concentration of about 3 uM in a solution comprising the target cell (e.g., described herein) for delivery to said target cell. In embodiments, the RNP is provided at a final concentration of about 1 uM in a solution comprising the target cell (e.g., described herein) for delivery to said target cell. In embodiments, the RNP is provided at a final concentration of about 0.3 uM in a solution comprising the target cell (e.g., described herein) for delivery to said target cell. In embodiments, the RNP is provided at a final concentration of about 0.1 uM in a solution comprising the target cell (e.g., described herein) for delivery to said target cell. In embodiments, the RNP is provided at a final concentration of about 0.05 uM in a solution comprising the target cell (e.g., described herein) for delivery to said target cell. In embodiments, the RNP is provided at a final concentration of about 0.03 uM in a solution comprising the target cell (e.g., described herein) for delivery to said target cell. In embodiments, the RNP is provided at a final concentration of about 0.01 uM in a solution comprising the target cell (e.g., described herein) for delivery to said target cell.

›TGTGAA · 11 of 11

XI. Methods of Treatment

The Cas systems, e.g., one or more gRNA molecules and one or more Cas molecules (e.g., Cas9 molecules), described herein are useful for the treatment of disease in a mammal, e.g., in a human. The terms “treat,” “treated,” “treating,” and “treatment,” include the administration of Cas systems, e.g., one or more gRNA molecules and one or more Cas9 molecules, to cells to prevent or delay the onset of the symptoms, complications, or biochemical indicia of a disease, alleviating the symptoms or arresting or inhibiting further development of the disease, condition, or disorder. Treatment may be prophylactic (to prevent or delay the onset of the disease, or to prevent the manifestation of clinical or subclinical symptoms thereof) or therapeutic suppression or alleviation of symptoms after the manifestation of the disease. Treatment can be measured by the therapeutic measures described herein. The methods of “treatment” of the present disclosure also include administration of cells altered by the introduction of a Cas system (e.g., one or more gRNA molecules and one or more Cas molecules) into said cells to a subject in order to cure, delay, reverse, reduce the severity of, or ameliorate one or more symptoms of a disease or condition, in order to prolong the health or survival of a subject beyond that expected in the absence of such treatment. For example, “treatment” includes the alleviation of a disease symptom in a subject by at least 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or more.

Methods of Treatment/Combination Therapies

In various embodiments, methods of administering cells to a subject are provided, e.g., T or NK cells, e.g., autologous or allogeneic T cells, e.g., described herein, (e.g., those that express a CAR and/or have been modified at a TET2 intron or a TET2 intron-exon as described herein). In some embodiments, the cell is generated using the CRISPR methods disclosed herein. Other methods for generating the cells may also be used.

In one embodiment, the method comprises administering a cell which comprises or which at any time comprised a gRNA molecule as described herein, to a subject. In embodiments, the cell has been altered by the introduction of the gRNA molecule such that the gene comprising sequence complementary to the gRNA molecule targeting domain is altered, such that expression of functional product of that gene is reduced or eliminated relative to an unmodified cell. In embodiments, the cell is further engineered to express a CAR, e.g., as described herein. In embodiments, the cell is an immune effector cell, e.g., an NK cell or T cell. In embodiments, the cell is allogeneic. In embodiments, the cell is autologous.

In another aspect, the present disclosure provides a method comprising administering a gRNA molecule, e.g., a gRNA molecule described herein, or a cell comprising or which at any time comprised a gRNA molecule, e.g., a gRNA molecule described herein, to a subject in need thereof. In one embodiment, the subject has a disorder described herein, e.g., the subject has cancer, e.g., the subject has a cancer which expresses a target antigen described herein. In one embodiment, the subject is a human.

In another aspect, the disclosure pertains to a method of treating a subject having a disease associated with expression of a cancer associated antigen as described herein comprising administering to the subject an effective amount of a gRNA molecule, e.g., a gRNA molecule described herein, or a cell comprising or which at any time comprised a gRNA molecule, e.g., a gRNA molecule described herein.

In yet another aspect, the disclosure features a method of treating a subject having a disease associated with expression of a tumor antigen (e.g., an antigen described herein), comprising administering to the subject an effective amount of a cell, e.g., an immune effector ce

›Tables in the description — 22
NCBI Reference
NameSequenceSequence
Homo sapiens
NM_001127208.2GGCAGTGGCAGCGGCGAGAGCTTGGGCGGCCGCCGCCG
tetCCTCCTCGCGAGCGCCGCGCGCCCGGGTCCCG
methylcytosineCTCGCATGCAAGTCACGTCCGCCCCCTCGGCGCGGCCGC
dioxygenase 2CCCGAGACGCCGGCCCCGCTGAGTGATGAGA
(TET2),ACAGACGTCAAACTGCCTTATGAATATTGATGCGGAGGC
transcriptTAGGCTGCTTTCGTAGAGAAGCAGAAGGAAG
variant 1,CAAGATGGCTGCCCTTTAGGATTTGTTAGAAAGGAGACC
mRNACGACTGCAACTGCTGGATTGCTGCAAGGCTG
[SEQ ID NO:AGGGACGAGAACGAGGCTGGCAAACATTCAGCAGCACA
951]CCCTCTCAAGATTGTTTACTTGCCTTTGCTCC
TGTTGAGTTACAACGCTTGGAAGCAGGAGATGGGCTCAG
CAGCAGCCAATAGGACATGATCCAGGAAGAG
CAGTAAGGGACTGAGCTGCTGAATTCAACTAGAGGGCA
GCCTTGTGGATGGCCCCGAAGCAAGCCTGATG
GAACAGGATAGAACCAACCATGTTGAGGGCAACAGACT
AAGTCCATTCCTGATACCATCACCTCCCATTT
GCCAGACAGAACCTCTGGCTACAAAGCTCCAGAATGGA
AGCCCACTGCCTGAGAGAGCTCATCCAGAAGT
AAATGGAGACACCAAGTGGCACTCTTTCAAAAGTTATTA
TGGAATACCCTGTATGAAGGGAAGCCAGAAT
AGTCGTGTGAGTCCTGACTTTACACAAGAAAGTAGAGGG
TATTCCAAGTGTTTGCAAAATGGAGGAATAA
AACGCACAGTTAGTGAACCTTCTCTCTCTGGGCTCCTTCA
GATCAAGAAATTGAAACAAGACCAAAAGGC
TAATGGAGAAAGACGTAACTTCGGGGTAAGCCAAGAAA
GAAATCCAGGTGAAAGCAGTCAACCAAATGTC
TCCGATTTGAGTGATAAGAAAGAATCTGTGAGTTCTGTA
GCCCAAGAAAATGCAGTTAAAGATTTCACCA
GTTTTTCAACACATAACTGCAGTGGGCCTGAAAATCCAG
AGCTTCAGATTCTGAATGAGCAGGAGGGGAA
AAGTGCTAATTACCATGACAAGAACATTGTATTACTTAA
AAACAAGGCAGTGCTAATGCCTAATGGTGCT
ACAGTTTCTGCCTCTTCCGTGGAACACACACATGGTGAA
CTCCTGGAAAAAACACTGTCTCAATATTATC
CAGATTGTGTTTCCATTGCGGTGCAGAAAACCACATCTC
ACATAAATGCCATTAACAGTCAGGCTACTAA
TGAGTTGTCCTGTGAGATCACTCACCCATCGCATACCTCA
GGGCAGATCAATTCCGCACAGACCTCTAAC
TCTGAGCTGCCTCCAAAGCCAGCTGCAGTGGTGAGTGAG
GCCTGTGATGCTGATGATGCTGATAATGCCA
GTAAACTAGCTGCAATGCTAAATACCTGTTCCTTTCAGA
AACCAGAACAACTACAACAACAAAAATCAGT
TTTTGAGATATGCCCATCTCCTGCAGAAAATAACATCCA
GGGAACCACAAAGCTAGCGTCTGGTGAAGAA
TTCTGTTCAGGTTCCAGCAGCAATTTGCAAGCTCCTGGTG
GCAGCTCTGAACGGTATTTAAAACAAAATG
AAATGAATGGTGCTTACTTCAAGCAAAGCTCAGTGTTCA
CTAAGGATTCCTTTTCTGCCACTACCACACC
ACCACCACCATCACAATTGCTTCTTTCTCCCCCTCCTCCT
CTTCCACAGGTTCCTCAGCTTCCTTCAGAA
GGAAAAAGCACTCTGAATGGTGGAGTTTTAGAAGAACA
CCACCACTACCCCAACCAAAGTAACACAACAC
TTTTAAGGGAAGTGAAAATAGAGGGTAAACCTGAGGCA
CCACCTTCCCAGAGTCCTAATCCATCTACACA
TGTATGCAGCCCTTCTCCGATGCTTTCTGAAAGGCCTCAG
AATAATTGTGTGAACAGGAATGACATACAG
ACTGCAGGGACAATGACTGTTCCATTGTGTTCTGAGAAA
ACAAGACCAATGTCAGAACACCTCAAGCATA
ACCCACCAATTTTTGGTAGCAGTGGAGAGCTACAGGACA
ACTGCCAGCAGTTGATGAGAAACAAAGAGCA
AGAGATTCTGAAGGGTCGAGACAAGGAGCAAACACGAG
ATCTTGTGCCCCCAACACAGCACTATCTGAAA
CCAGGATGGATTGAATTGAAGGCCCCTCGTTTTCACCAA
GCGGAATCCCATCTAAAACGTAATGAGGCAT
CACTGCCATCAATTCTTCAGTATCAACCCAATCTCTCCAA
TCAAATGACCTCCAAACAATACACTGGAAA
TTCCAACATGCCTGGGGGGCTCCCAAGGCAAGCTTACAC
CCAGAAAACAACACAGCTGGAGCACAAGTCA
CAAATGTACCAAGTTGAAATGAATCAAGGGCAGTCCCAA
GGTACAGTGGACCAACATCTCCAGTTCCAAA
AACCCTCACACCAGGTGCACTTCTCCAAAACAGACCATT
TACCAAAAGCTCATGTGCAGTCACTGTGTGG
CACTAGATTTCATTTTCAACAAAGAGCAGATTCCCAAAC
TGAAAAACTTATGTCCCCAGTGTTGAAACAG
CACTTGAATCAACAGGCTTCAGAGACTGAGCCATTTTCA
AACTCACACCTTTTGCAACATAAGCCTCATA
AACAGGCAGCACAAACACAACCATCCCAGAGTTCACATC
TCCCTCAAAACCAGCAACAGCAGCAAAAATT
ACAAATAAAGAATAAAGAGGAAATACTCCAGACTTTTCC
TCACCCCCAAAGCAACAATGATCAGCAAAGA
GAAGGATCATTCTTTGGCCAGACTAAAGTGGAAGAATGT
TTTCATGGTGAAAATCAGTATTCAAAATCAA
GCGAGTTCGAGACTCATAATGTCCAAATGGGACTGGAGG
AAGTACAGAATATAAATCGTAGAAATTCCCC
TTATAGTCAGACCATGAAATCAAGTGCATGCAAAATACA
GGTTTCTTGTTCAAACAATACACACCTAGTT
TCAGAGAATAAAGAACAGACTACACATCCTGAACTTTTT
GCAGGAAACAAGACCCAAAACTTGCATCACA
TGCAATATTTTCCAAATAATGTGATCCCAAAGCAAGATC
TTCTTCACAGGTGCTTTCAAGAACAGGAGCA
GAAGTCACAACAAGCTTCAGTTCTACAGGGATATAAAAA
TAGAAACCAAGATATGTCTGGTCAACAAGCT
GCGCAACTTGCTCAGCAAAGGTACTTGATACATAACCAT
GCAAATGTTTTTCCTGTGCCTGACCAGGGAG
GAAGTCACACTCAGACCCCTCCCCAGAAGGACACTCAAA
AGCATGCTGCTCTAAGGTGGCATCTCTTACA
GAAGCAAGAACAGCAGCAAACACAGCAACCCCAAACTG
AGTCTTGCCATAGTCAGATGCACAGGCCAATT
AAGGTGGAACCTGGATGCAAGCCACATGCCTGTATGCAC
ACAGCACCACCAGAAAACAAAACATGGAAAA
AGGTAACTAAGCAAGAGAATCCACCTGCAAGCTGTGATA
ATGTGCAGCAAAAGAGCATCATTGAGACCAT
GGAGCAGCATCTGAAGCAGTTTCACGCCAAGTCGTTATT
TGACCATAAGGCTCTTACTCTCAAATCACAG
AAGCAAGTAAAAGTTGAAATGTCAGGGCCAGTCACAGTT
TTGACTAGACAAACCACTGCTGCAGAACTTG
ATAGCCACACCCCAGCTTTAGAGCAGCAAACAACTTCTT
CAGAAAAGACACCAACCAAAAGAACAGCTGC
TTCTGTTCTCAATAATTTTATAGAGTCACCTTCCAAATTA
CTAGATACTCCTATAAAAAATTTATTGGAT
ACACCTGTCAAGACTCAATATGATTTCCCATCTTGCAGAT
GTGTAGAGCAAATTATTGAAAAAGATGAAG
GTCCTTTTTATACCCATCTAGGAGCAGGTCCTAATGTGGC
AGCTATTAGAGAAATCATGGAAGAAAGGTT
TGGACAGAAGGGTAAAGCTATTAGGATTGAAAGAGTCA
TCTATACTGGTAAAGAAGGCAAAAGTTCTCAG
GGATGTCCTATTGCTAAGTGGGTGGTTCGCAGAAGCAGC
AGTGAAGAGAAGCTACTGTGTTTGGTGCGGG
AGCGAGCTGGCCACACCTGTGAGGCTGCAGTGATTGTGA
TTCTCATCCTGGTGTGGGAAGGAATCCCGCT
GTCTCTGGCTGACAAACTCTACTCGGAGCTTACCGAGAC
GCTGAGGAAATACGGCACGCTCACCAATCGC
CGGTGTGCCTTGAATGAAGAGAGAACTTGCGCCTGTCAG
GGGCTGGATCCAGAAACCTGTGGTGCCTCCT
TCTCTTTTGGTTGTTCATGGAGCATGTACTACAATGGATG
TAAGTTTGCCAGAAGCAAGATCCCAAGGAA
GTTTAAGCTGCTTGGGGATGACCCAAAAGAGGAAGAGA
AACTGGAGTCTCATTTGCAAAACCTGTCCACT
CTTATGGCACCAACATATAAGAAACTTGCACCTGATGCA
TATAATAATCAGATTGAATATGAACACAGAG
CACCAGAGTGCCGTCTGGGTCTGAAGGAAGGCCGTCCAT
TCTCAGGGGTCACTGCATGTTTGGACTTCTG
TGCTCATGCCCACAGAGACTTGCACAACATGCAGAATGG
CAGCACATTGGTATGCACTCTCACTAGAGAA
GACAATCGAGAATTTGGAGGAAAACCTGAGGATGAGCA
GCTTCACGTTCTGCCTTTATACAAAGTCTCTG
ACGTGGATGAGTTTGGGAGTGTGGAAGCTCAGGAGGAG
AAAAAACGGAGTGGTGCCATTCAGGTACTGAG
TTCTTTTCGGCGAAAAGTCAGGATGTTAGCAGAGCCAGT
CAAGACTTGCCGACAAAGGAAACTAGAAGCC
AAGAAAGCTGCAGCTGAAAAGCTTTCCTCCCTGGAGAAC
AGCTCAAATAAAAATGAAAAGGAAAAGTCAG
CCCCATCACGTACAAAACAAACTGAAAACGCAAGCCAG
GCTAAACAGTTGGCAGAACTTTTGCGACTTTC
AGGACCAGTCATGCAGCAGTCCCAGCAGCCCCAGCCTCT
ACAGAAGCAGCCACCACAGCCCCAGCAGCAG
CAGAGACCCCAGCAGCAGCAGCCACATCACCCTCAGAC
AGAGTCTGTCAACTCTTATTCTGCTTCTGGAT
CCACCAATCCATACATGAGACGGCCCAATCCAGTTAGTC
CTTATCCAAACTCTTCACACACTTCAGATAT
CTATGGAAGCACCAGCCCTATGAACTTCTATTCCACCTC
ATCTCAAGCTGCAGGTTCATATTTGAATTCT
TCTAATCCCATGAACCCTTACCCTGGGCTTTTGAATCAGA
ATACCCAATATCCATCATATCAATGCAATG
GAAACCTATCAGTGGACAACTGCTCCCCATATCTGGGTT
CCTATTCTCCCCAGTCTCAGCCGATGGATCT
GTATAGGTATCCAAGCCAAGACCCTCTGTCTAAGCTCAG
TCTACCACCCATCCATACACTTTACCAGCCA
AGGTTTGGAAATAGCCAGAGTTTTACATCTAAATACTTA
GGTTATGGAAACCAAAATATGCAGGGAGATG
GTTTCAGCAGTTGTACCATTAGACCAAATGTACATCATG
TAGGGAAATTGCCTCCTTATCCCACTCATGA
GATGGATGGCCACTTCATGGGAGCCACCTCTAGATTACC
ACCCAATCTGAGCAATCCAAACATGGACTAT
AAAAATGGTGAACATCATTCACCTTCTCACATAATCCAT
AACTACAGTGCAGCTCCGGGCATGTTCAACA
GCTCTCTTCATGCCCTGCATCTCCAAAACAAGGAGAATG
ACATGCTTTCCCACACAGCTAATGGGTTATC
AAAGATGCTTCCAGCTCTTAACCATGATAGAACTGCTTG
TGTCCAAGGAGGCTTACACAAATTAAGTGAT
GCTAATGGTCAGGAAAAGCAGCCATTGGCACTAGTCCAG
GGTGTGGCTTCTGGTGCAGAGGACAACGATG
AGGTCTGGTCAGACAGCGAGCAGAGCTTTCTGGATCCTG
ACATTGGGGGAGTGGCCGTGGCTCCAACTCA
TGGGTCAATTCTCATTGAGTGTGCAAAGCGTGAGCTGCA
TGCCACAACCCCTTTAAAGAATCCCAATAGG
AATCACCCCACCAGGATCTCCCTCGTCTTTTACCAGCATA
AGAGCATGAATGAGCCAAAACATGGCTTGG
CTCTTTGGGAAGCCAAAATGGCTGAAAAAGCCCGTGAGA
AAGAGGAAGAGTGTGAAAAGTATGGCCCAGA
CTATGTGCCTCAGAAATCCCATGGCAAAAAAGTGAAACG
GGAGCCTGCTGAGCCACATGAAACTTCAGAG
CCCACTTACCTGCGTTTCATCAAGTCTCTTGCCGAAAGGA
CCATGTCCGTGACCACAGACTCCACAGTAA
CTACATCTCCATATGCCTTCACTCGGGTCACAGGGCCTTA
CAACAGATATATATGATATCACCCCCTTTT
GTTGGTTACCTCACTTGAAAAGACCACAACCAACCTGTC
AGTAGTATAGTTCTCATGACGTGGGCAGTGG
GGAAAGGTCACAGTATTCATGACAAATGTGGTGGGAAA
AACCTCAGCTCACCAGCAACAAAAGAGGTTAT
CTTACCATAGCACTTAATTTTCACTGGCTCCCAAGTGGTC
ACAGATGGCATCTAGGAAAAGACCAAAGCA
TTCTATGCAAAAAGAAGGTGGGGAAGAAAGTGTTCCGC
AATTTACATTTTTAAACACTGGTTCTATTATT
GGACGAGATGATATGTAAATGTGATCCCCCCCCCCCGCT
TACAACTCTACACATCTGTGACCACTTTTAA
TAATATCAAGTTTGCATAGTCATGGAACACAAATCAAAC
AAGTACTGTAGTATTACAGTGACAGGAATCT
TAAAATACCATCTGGTGCTGAATATATGATGTACTGAAA
TACTGGAATTATGGCTTTTTGAAATGCAGTT
TTTACTGTAATCTTAACTTTTATTTATCAAAATAGCTACA
GGAAACATGAATAGCAGGAAAACACTGAAT
TTGTTTGGATGTTCTAAGAAATGGTGCTAAGAAAATGGT
GTCTTTAATAGCTAAAAATTTAATGCCTTTA
TATCATCAAGATGCTATCAGTGTACTCCAGTGCCCTTGA
ATAATAGGGGTACCTTTTCATTCAAGTTTTT
ATCATAATTACCTATTCTTACACAAGCTTAGTTTTTAAAA
TGTGGACATTTTAAAGGCCTCTGGATTTTG
CTCATCCAGTGAAGTCCTTGTAGGACAATAAACGTATAT
ATGTACATATATACACAAACATGTATATGTG
CACACACATGTATATGTATAAATATTTTAAATGGTGTTTT
AGAAGCACTTTGTCTACCTAAGCTTTGACA
ACTTGAACAATGCTAAGGTACTGAGATGTTTAAAAAACA
AGTTTACTTTCATTTTAGAATGCAAAGTTGA
TTTTTTTAAGGAAACAAAGAAAGCTTTTAAAATATTTTTG
CTTTTAGCCATGCATCTGCTGATGAGCAAT
TGTGTCCATTTTTAACACAGCCAGTTAAATCCACCATGG
GGCTTACTGGATTCAAGGGAATACGTTAGTC
CACAAAACATGTTTTCTGGTGCTCATCTCACATGCTATAC
TGTAAAACAGTTTTATACAAAATTGTATGA
CAAGTTCATTGCTCAAAAATGTACAGTTTTAAGAATTTTC
TATTAACTGCAGGTAATAATTAGCTGCATG
CTGCAGACTCAACAAAGCTAGTTCACTGAAGCCTATGCT
ATTTTATGGATCATAGGCTCTTCAGAGAACT
GAATGGCAGTCTGCCTTTGTGTTGATAATTATGTACATTG
TGACGTTGTCATTTCTTAGCTTAAGTGTCC
TCTTTAACAAGAGGATTGAGCAGACTGATGCCTGCATAA
GATGAATAAACAGGGTTAGTTCCATGTGAAT
CTGTCAGTTAAAAAGAAACAAAAACAGGCAGCTGGTTTG
CTGTGGTGGTTTTAAATCATTAATTTGTATA
AAGAAGTGAAAGAGTTGTATAGTAAATTAAATTGTAAAC
AAAACTTTTTTAATGCAATGCTTTAGTATTT
TAGTACTGTAAAAAAATTAAATATATACATATATATATA
TATATATATATATATATATATGAGTTTGAAG
CAGAATTCACATCATGATGGTGCTACTCAGCCTGCTACA
AATATATCATAATGTGAGCTAAGAATTCATT
AAATGTTTGAGTGATGTTCCTACTTGTCATATACCTCAAC
ACTAGTTTGGCAATAGGATATTGAACTGAG
AGTGAAAGCATTGTGTACCATCATTTTTTTCCAAGTCCTT
TTTTTTATTGTTAAAAAAAAAAGCATACCT
TTTTTCAATACTTGATTTCTTAGCAAGTATAACTTGAACT
TCAACCTTTTTGTTCTAAAAATTCAGGGAT
ATTTCAGCTCATGCTCTCCCTATGCCAACATGTCACCTGT
GTTTATGTAAAATTGTTGTAGGTTAATAAA
TATATTCTTTGTCAGGGATTTAACCCTTTTATTTTGAATC
CCTTCTATTTTACTTGTACATGTGCTGATG
TAACTAAAACTAATTTTGTAAATCTGTTGGCTCTTTTTAT
TGTAAAGAAAAGCATTTTAAAAGTTTGAGG
AATCTTTTGACTGTTTCAAGCAGGAAAAAAAAATTACAT
GAAAATAGAATGCACTGAGTTGATAAAGGGA
AAAATTGTAAGGCAGGAGTTTGGCAAGTGGCTGTTGGCC
AGAGACTTACTTGTAACTCTCTAAATGAAGT
TTTTTTGATCCTGTAATCACTGAAGGTACATACTCCATGT
GGACTTCCCTTAAACAGGCAAACACCTACA
GGTATGGTGTGCAACAGATTGTACAATTACATTTTGGCC
TAAATACATTTTTGCTTACTAGTATTTAAAA
TAAATTCTTAATCAGAGGAGGCCTTTGGGTTTTATTGGTC
AAATCTTTGTAAGCTGGCTTTTGTCTTTTT
AAAAAATTTCTTGAATTTGTGGTTGTGTCCAATTTGCAAA
CATTTCCAAAAATGTTTGCTTTGCTTACAA
ACCACATGATTTTAATGTTTTTTGTATACCATAATATCTA
GCCCCAAACATTTGATTACTACATGTGCAT
TGGTGATTTTGATCATCCATTCTTAATATTTGATTTCTGT
GTCACCTACTGTCATTTGTTAAACTGCTGG
CCAACAAGAACAGGAAGTATAGTTTGGGGGGTTGGGGA
GAGTTTACATAAGGAAGAGAAGAAATTGAGTG
GCATATTGTAAATATCAGATCTATAATTGTAAATATAAA
ACCTGCCTCAGTTAGAATGAATGGAAAGCAG
ATCTACAATTTGCTAATATAGGAATATCAGGTTGACTAT
ATAGCCATACTTGAAAATGCTTCTGAGTGGT
GTCAACTTTACTTGAATGAATTTTTCATCTTGATTGACGC
ACAGTGATGTACAGTTCACTTCTGAAGCTA
GTGGTTAACTTGTGTAGGAAACTTTTGCAGTTTGACACTA
AGATAACTTCTGTGTGCATTTTTCTATGCT
TTTTTAAAAACTAGTTTCATTTCATTTTCATGAGATGTTT
GGTTTATAAGATCTGAGGATGGTTATAAAT
ACTGTAAGTATTGTAATGTTATGAATGCAGGTTATTTGA
AAGCTGTTTATTATTATATCATTCCTGATAA
TGCTATGTGAGTGTTTTTAATAAAATTTATATTTATTTAA
TGCACTCTAAAAAAAAAAAAAAAAAA
PREDICTED:XM_005263082.1AAGCAGAAGGAAGCAAGATGGCTGCCCTTTAGGATTTGT
Homo sapiens
TAGAAAGGAGACCCGACTGCAACTGCTGGAT
tetTGCTGCAAGGCTGAGGGACGAGAACGAGAATTCAACTA
methylcytosineGAGGGCAGCCTTGTGGATGGCCCCGAAGCAAG
dioxygenase 2CCTGATGGAACAGGATAGAACCAACCATGTTGAGGGCA
(TET2),ACAGACTAAGTCCATTCCTGATACCATCACCT
transcriptCCCATTTGCCAGACAGAACCTCTGGCTACAAAGCTCCAG
variant X1,AATGGAAGCCCACTGCCTGAGAGAGCTCATC
mRNACAGAAGTAAATGGAGACACCAAGTGGCACTCTTTCAAAA
[SEQ ID NO:GTTATTATGGAATACCCTGTATGAAGGGAAG
952]CCAGAATAGTCGTGTGAGTCCTGACTTTACACAAGAAAG
TAGAGGGTATTCCAAGTGTTTGCAAAATGGA
GGAATAAAACGCACAGTTAGTGAACCTTCTCTCTCTGGG
CTCCTTCAGATCAAGAAATTGAAACAAGACC
AAAAGGCTAATGGAGAAAGACGTAACTTCGGGGTAAGC
CAAGAAAGAAATCCAGGTGAAAGCAGTCAACC
AAATGTCTCCGATTTGAGTGATAAGAAAGAATCTGTGAG
TTCTGTAGCCCAAGAAAATGCAGTTAAAGAT
TTCACCAGTTTTTCAACACATAACTGCAGTGGGCCTGAA
AATCCAGAGCTTCAGATTCTGAATGAGCAGG
AGGGGAAAAGTGCTAATTACCATGACAAGAACATTGTAT
TACTTAAAAACAAGGCAGTGCTAATGCCTAA
TGGTGCTACAGTTTCTGCCTCTTCCGTGGAACACACACAT
GGTGAACTCCTGGAAAAAACACTGTCTCAA
TATTATCCAGATTGTGTTTCCATTGCGGTGCAGAAAACC
ACATCTCACATAAATGCCATTAACAGTCAGG
CTACTAATGAGTTGTCCTGTGAGATCACTCACCCATCGC
ATACCTCAGGGCAGATCAATTCCGCACAGAC
CTCTAACTCTGAGCTGCCTCCAAAGCCAGCTGCAGTGGT
GAGTGAGGCCTGTGATGCTGATGATGCTGAT
AATGCCAGTAAACTAGCTGCAATGCTAAATACCTGTTCC
TTTCAGAAACCAGAACAACTACAACAACAAA
AATCAGTTTTTGAGATATGCCCATCTCCTGCAGAAAATA
ACATCCAGGGAACCACAAAGCTAGCGTCTGG
TGAAGAATTCTGTTCAGGTTCCAGCAGCAATTTGCAAGC
TCCTGGTGGCAGCTCTGAACGGTATTTAAAA
CAAAATGAAATGAATGGTGCTTACTTCAAGCAAAGCTCA
GTGTTCACTAAGGATTCCTTTTCTGCCACTA
CCACACCACCACCACCATCACAATTGCTTCTTTCTCCCCC
TCCTCCTCTTCCACAGGTTCCTCAGCTTCC
TTCAGAAGGAAAAAGCACTCTGAATGGTGGAGTTTTAGA
AGAACACCACCACTACCCCAACCAAAGTAAC
ACAACACTTTTAAGGGAAGTGAAAATAGAGGGTAAACC
TGAGGCACCACCTTCCCAGAGTCCTAATCCAT
CTACACATGTATGCAGCCCTTCTCCGATGCTTTCTGAAAG
GCCTCAGAATAATTGTGTGAACAGGAATGA
CATACAGACTGCAGGGACAATGACTGTTCCATTGTGTTC
TGAGAAAACAAGACCAATGTCAGAACACCTC
AAGCATAACCCACCAATTTTTGGTAGCAGTGGAGAGCTA
CAGGACAACTGCCAGCAGTTGATGAGAAACA
AAGAGCAAGAGATTCTGAAGGGTCGAGACAAGGAGCAA
ACACGAGATCTTGTGCCCCCAACACAGCACTA
TCTGAAACCAGGATGGATTGAATTGAAGGCCCCTCGTTT
TCACCAAGCGGAATCCCATCTAAAACGTAAT
GAGGCATCACTGCCATCAATTCTTCAGTATCAACCCAAT
CTCTCCAATCAAATGACCTCCAAACAATACA
CTGGAAATTCCAACATGCCTGGGGGGCTCCCAAGGCAAG
CTTACACCCAGAAAACAACACAGCTGGAGCA
CAAGTCACAAATGTACCAAGTTGAAATGAATCAAGGGC
AGTCCCAAGGTACAGTGGACCAACATCTCCAG
TTCCAAAAACCCTCACACCAGGTGCACTTCTCCAAAACA
GACCATTTACCAAAAGCTCATGTGCAGTCAC
TGTGTGGCACTAGATTTCATTTTCAACAAAGAGCAGATT
CCCAAACTGAAAAACTTATGTCCCCAGTGTT
GAAACAGCACTTGAATCAACAGGCTTCAGAGACTGAGCC
ATTTTCAAACTCACACCTTTTGCAACATAAG
CCTCATAAACAGGCAGCACAAACACAACCATCCCAGAGT
TCACATCTCCCTCAAAACCAGCAACAGCAGC
AAAAATTACAAATAAAGAATAAAGAGGAAATACTCCAG
ACTTTTCCTCACCCCCAAAGCAACAATGATCA
GCAAAGAGAAGGATCATTCTTTGGCCAGACTAAAGTGGA
AGAATGTTTTCATGGTGAAAATCAGTATTCA
AAATCAAGCGAGTTCGAGACTCATAATGTCCAAATGGGA
CTGGAGGAAGTACAGAATATAAATCGTAGAA
ATTCCCCTTATAGTCAGACCATGAAATCAAGTGCATGCA
AAATACAGGTTTCTTGTTCAAACAATACACA
CCTAGTTTCAGAGAATAAAGAACAGACTACACATCCTGA
ACTTTTTGCAGGAAACAAGACCCAAAACTTG
CATCACATGCAATATTTTCCAAATAATGTGATCCCAAAG
CAAGATCTTCTTCACAGGTGCTTTCAAGAAC
AGGAGCAGAAGTCACAACAAGCTTCAGTTCTACAGGGAT
ATAAAAATAGAAACCAAGATATGTCTGGTCA
ACAAGCTGCGCAACTTGCTCAGCAAAGGTACTTGATACA
TAACCATGCAAATGTTTTTCCTGTGCCTGAC
CAGGGAGGAAGTCACACTCAGACCCCTCCCCAGAAGGA
CACTCAAAAGCATGCTGCTCTAAGGTGGCATC
TCTTACAGAAGCAAGAACAGCAGCAAACACAGCAACCC
CAAACTGAGTCTTGCCATAGTCAGATGCACAG
GCCAATTAAGGTGGAACCTGGATGCAAGCCACATGCCTG
TATGCACACAGCACCACCAGAAAACAAAACA
TGGAAAAAGGTAACTAAGCAAGAGAATCCACCTGCAAG
CTGTGATAATGTGCAGCAAAAGAGCATCATTG
AGACCATGGAGCAGCATCTGAAGCAGTTTCACGCCAAGT
CGTTATTTGACCATAAGGCTCTTACTCTCAA
ATCACAGAAGCAAGTAAAAGTTGAAATGTCAGGGCCAG
TCACAGTTTTGACTAGACAAACCACTGCTGCA
GAACTTGATAGCCACACCCCAGCTTTAGAGCAGCAAACA
ACTTCTTCAGAAAAGACACCAACCAAAAGAA
CAGCTGCTTCTGTTCTCAATAATTTTATAGAGTCACCTTC
CAAATTACTAGATACTCCTATAAAAAATTT
ATTGGATACACCTGTCAAGACTCAATATGATTTCCCATCT
TGCAGATGTGTAGAGCAAATTATTGAAAAA
GATGAAGGTCCTTTTTATACCCATCTAGGAGCAGGTCCT
AATGTGGCAGCTATTAGAGAAATCATGGAAG
AAAGGTTTGGACAGAAGGGTAAAGCTATTAGGATTGAA
AGAGTCATCTATACTGGTAAAGAAGGCAAAAG
TTCTCAGGGATGTCCTATTGCTAAGTGGGTGGTTCGCAG
AAGCAGCAGTGAAGAGAAGCTACTGTGTTTG
GTGCGGGAGCGAGCTGGCCACACCTGTGAGGCTGCAGTG
ATTGTGATTCTCATCCTGGTGTGGGAAGGAA
TCCCGCTGTCTCTGGCTGACAAACTCTACTCGGAGCTTAC
CGAGACGCTGAGGAAATACGGCACGCTCAC
CAATCGCCGGTGTGCCTTGAATGAAGAGAGAACTTGCGC
CTGTCAGGGGCTGGATCCAGAAACCTGTGGT
GCCTCCTTCTCTTTTGGTTGTTCATGGAGCATGTACTACA
ATGGATGTAAGTTTGCCAGAAGCAAGATCC
CAAGGAAGTTTAAGCTGCTTGGGGATGACCCAAAAGAG
GAAGAGAAACTGGAGTCTCATTTGCAAAACCT
GTCCACTCTTATGGCACCAACATATAAGAAACTTGCACC
TGATGCATATAATAATCAGATTGAATATGAA
CACAGAGCACCAGAGTGCCGTCTGGGTCTGAAGGAAGG
CCGTCCATTCTCAGGGGTCACTGCATGTTTGG
ACTTCTGTGCTCATGCCCACAGAGACTTGCACAACATGC
AGAATGGCAGCACATTGGTATGCACTCTCAC
TAGAGAAGACAATCGAGAATTTGGAGGAAAACCTGAGG
ATGAGCAGCTTCACGTTCTGCCTTTATACAAA
GTCTCTGACGTGGATGAGTTTGGGAGTGTGGAAGCTCAG
GAGGAGAAAAAACGGAGTGGTGCCATTCAGG
TACTGAGTTCTTTTCGGCGAAAAGTCAGGATGTTAGCAG
AGCCAGTCAAGACTTGCCGACAAAGGAAACT
AGAAGCCAAGAAAGCTGCAGCTGAAAAGCTTTCCTCCCT
GGAGAACAGCTCAAATAAAAATGAAAAGGAA
AAGTCAGCCCCATCACGTACAAAACAAACTGAAAACGC
AAGCCAGGCTAAACAGTTGGCAGAACTTTTGC
GACTTTCAGGACCAGTCATGCAGCAGTCCCAGCAGCCCC
AGCCTCTACAGAAGCAGCCACCACAGCCCCA
GCAGCAGCAGAGACCCCAGCAGCAGCAGCCACATCACC
CTCAGACAGAGTCTGTCAACTCTTATTCTGCT
TCTGGATCCACCAATCCATACATGAGACGGCCCAATCCA
GTTAGTCCTTATCCAAACTCTTCACACACTT
CAGATATCTATGGAAGCACCAGCCCTATGAACTTCTATT
CCACCTCATCTCAAGCTGCAGGTTCATATTT
GAATTCTTCTAATCCCATGAACCCTTACCCTGGGCTTTTG
AATCAGAATACCCAATATCCATCATATCAA
TGCAATGGAAACCTATCAGTGGACAACTGCTCCCCATAT
CTGGGTTCCTATTCTCCCCAGTCTCAGCCGA
TGGATCTGTATAGGTATCCAAGCCAAGACCCTCTGTCTA
AGCTCAGTCTACCACCCATCCATACACTTTA
CCAGCCAAGGTTTGGAAATAGCCAGAGTTTTACATCTAA
ATACTTAGGTTATGGAAACCAAAATATGCAG
GGAGATGGTTTCAGCAGTTGTACCATTAGACCAAATGTA
CATCATGTAGGGAAATTGCCTCCTTATCCCA
CTCATGAGATGGATGGCCACTTCATGGGAGCCACCTCTA
GATTACCACCCAATCTGAGCAATCCAAACAT
GGACTATAAAAATGGTGAACATCATTCACCTTCTCACAT
AATCCATAACTACAGTGCAGCTCCGGGCATG
TTCAACAGCTCTCTTCATGCCCTGCATCTCCAAAACAAG
GAGAATGACATGCTTTCCCACACAGCTAATG
GGTTATCAAAGATGCTTCCAGCTCTTAACCATGATAGAA
CTGCTTGTGTCCAAGGAGGCTTACACAAATT
AAGTGATGCTAATGGTCAGGAAAAGCAGCCATTGGCACT
AGTCCAGGGTGTGGCTTCTGGTGCAGAGGAC
AACGATGAGGTCTGGTCAGACAGCGAGCAGAGCTTTCTG
GATCCTGACATTGGGGGAGTGGCCGTGGCTC
CAACTCATGGGTCAATTCTCATTGAGTGTGCAAAGCGTG
AGCTGCATGCCACAACCCCTTTAAAGAATCC
CAATAGGAATCACCCCACCAGGATCTCCCTCGTCTTTTAC
CAGCATAAGAGCATGAATGAGCCAAAACAT
GGCTTGGCTCTTTGGGAAGCCAAAATGGCTGAAAAAGCC
CGTGAGAAAGAGGAAGAGTGTGAAAAGTATG
GCCCAGACTATGTGCCTCAGAAATCCCATGGCAAAAAAG
TGAAACGGGAGCCTGCTGAGCCACATGAAAC
TTCAGAGCCCACTTACCTGCGTTTCATCAAGTCTCTTGCC
GAAAGGACCATGTCCGTGACCACAGACTCC
ACAGTAACTACATCTCCATATGCCTTCACTCGGGTCACA
GGGCCTTACAACAGATATATATGATATCACC
CCCTTTTGTTGGTTACCTCACTTGAAAAGACCACAACCA
ACCTGTCAGTAGTATAGTTCTCATGACGTGG
GCAGTGGGGAAAGGTCACAGTATTCATGACAAATGTGGT
GGGAAAAACCTCAGCTCACCAGCAACAAAAG
AGGTTATCTTACCATAGCACTTAATTTTCACTGGCTCCCA
AGTGGTCACAGATGGCATCTAGGAAAAGAC
CAAAGCATTCTATGCAAAAAGAAGGTGGGGAAGAAAGT
GTTCCGCAATTTACATTTTTAAACACTGGTTC
TATTATTGGACGAGATGATATGTAAATGTGATCCCCCCC
CCCCGCTTACAACTCTACACATCTGTGACCA
CTTTTAATAATATCAAGTTTGCATAGTCATGGAACACAA
ATCAAACAAGTACTGTAGTATTACAGTGACA
GGAATCTTAAAATACCATCTGGTGCTGAATATATGATGT
ACTGAAATACTGGAATTATGGCTTTTTGAAA
TGCAGTTTTTACTGTAATCTTAACTTTTATTTATCAAAAT
AGCTACAGGAAACATGAATAGCAGGAAAAC
ACTGAATTTGTTTGGATGTTCTAAGAAATGGTGCTAAGA
AAATGGTGTCTTTAATAGCTAAAAATTTAAT
GCCTTTATATCATCAAGATGCTATCAGTGTACTCCAGTGC
CCTTGAATAATAGGGGTACCTTTTCATTCA
AGTTTTTATCATAATTACCTATTCTTACACAAGCTTAGTT
TTTAAAATGTGGACATTTTAAAGGCCTCTG
GATTTTGCTCATCCAGTGAAGTCCTTGTAGGACAATAAA
CGTATATATGTACATATATACACAAACATGT
ATATGTGCACACACATGTATATGTATAAATATTTTAAAT
GGTGTTTTAGAAGCACTTTGTCTACCTAAGC
TTTGACAACTTGAACAATGCTAAGGTACTGAGATGTTTA
AAAAACAAGTTTACTTTCATTTTAGAATGCA
AAGTTGATTTTTTTAAGGAAACAAAGAAAGCTTTTAAAA
TATTTTTGCTTTTAGCCATGCATCTGCTGAT
GAGCAATTGTGTCCATTTTTAACACAGCCAGTTAAATCC
ACCATGGGGCTTACTGGATTCAAGGGAATAC
GTTAGTCCACAAAACATGTTTTCTGGTGCTCATCTCACAT
GCTATACTGTAAAACAGTTTTATACAAAAT
TGTATGACAAGTTCATTGCTCAAAAATGTACAGTTTTAA
GAATTTTCTATTAACTGCAGGTAATAATTAG
CTGCATGCTGCAGACTCAACAAAGCTAGTTCACTGAAGC
CTATGCTATTTTATGGATCATAGGCTCTTCA
GAGAACTGAATGGCAGTCTGCCTTTGTGTTGATAATTAT
GTACATTGTGACGTTGTCATTTCTTAGCTTA
AGTGTCCTCTTTAACAAGAGGATTGAGCAGACTGATGCC
TGCATAAGATGAATAAACAGGGTTAGTTCCA
TGTGAATCTGTCAGTTAAAAAGAAACAAAAACAGGCAG
CTGGTTTGCTGTGGTGGTTTTAAATCATTAAT
TTGTATAAAGAAGTGAAAGAGTTGTATAGTAAATTAAAT
TGTAAACAAAACTTTTTTAATGCAATGCTTT
AGTATTTTAGTACTGTAAAAAAATTAAATATATACATAT
ATATATATATATATATATATATATATATGAG
TTTGAAGCAGAATTCACATCATGATGGTGCTACTCAGCC
TGCTACAAATATATCATAATGTGAGCTAAGA
ATTCATTAAATGTTTGAGTGATGTTCCTACTTGTCATATA
CCTCAACACTAGTTTGGCAATAGGATATTG
AACTGAGAGTGAAAGCATTGTGTACCATCATTTTTTTCCA
AGTCCTTTTTTTTATTGTTAAAAAAAAAAG
CATACCTTTTTTCAATACTTGATTTCTTAGCAAGTATAAC
TTGAACTTCAACCTTTTTGTTCTAAAAATT
CAGGGATATTTCAGCTCATGCTCTCCCTATGCCAACATGT
CACCTGTGTTTATGTAAAATTGTTGTAGGT
TAATAAATATATTCTTTGTCAGGGATTTAACCCTTTTATT
TTGAATCCCTTCTATTTTACTTGTACATGT
GCTGATGTAACTAAAACTAATTTTGTAAATCTGTTGGCTC
TTTTTATTGTAAAGAAAAGCATTTTAAAAG
TTTGAGGAATCTTTTGACTGTTTCAAGCAGGAAAAAAAA
ATTACATGAAAATAGAATGCACTGAGTTGAT
AAAGGGAAAAATTGTAAGGCAGGAGTTTGGCAAGTGGC
TGTTGGCCAGAGACTTACTTGTAACTCTCTAA
ATGAAGTTTTTTTGATCCTGTAATCACTGAAGGTACATAC
TCCATGTGGACTTCCCTTAAACAGGCAAAC
ACCTACAGGTATGGTGTGCAACAGATTGTACAATTACAT
TTTGGCCTAAATACATTTTTGCTTACTAGTA
TTTAAAATAAATTCTTAATCAGAGGAGGCCTTTGGGTTTT
ATTGGTCAAATCTTTGTAAGCTGGCTTTTG
TCTTTTTAAAAAATTTCTTGAATTTGTGGTTGTGTCCAAT
TTGCAAACATTTCCAAAAATGTTTGCTTTG
CTTACAAACCACATGATTTTAATGTTTTTTGTATACCATA
ATATCTAGCCCCAAACATTTGATTACTACA
TGTGCATTGGTGATTTTGATCATCCATTCTTAATATTTGA
TTTCTGTGTCACCTACTGTCATTTGTTAAA
CTGCTGGCCAACAAGAACAGGAAGTATAGTTTGGGGGGT
TGGGGAGAGTTTACATAAGGAAGAGAAGAAA
TTGAGTGGCATATTGTAAATATCAGATCTATAATTGTAA
ATATAAAACCTGCCTCAGTTAGAATGAATGG
AAAGCAGATCTACAATTTGCTAATATAGGAATATCAGGT
TGACTATATAGCCATACTTGAAAATGCTTCT
GAGTGGTGTCAACTTTACTTGAATGAATTTTTCATCTTGA
TTGACGCACAGTGATGTACAGTTCACTTCT
GAAGCTAGTGGTTAACTTGTGTAGGAAACTTTTGCAGTT
TGACACTAAGATAACTTCTGTGTGCATTTTT
CTATGCTTTTTTAAAAACTAGTTTCATTTCATTTTCATGA
GATGTTTGGTTTATAAGATCTGAGGATGGT
TATAAATACTGTAAGTATTGTAATGTTATGAATGCAGGT
TATTTGAAAGCTGTTTATTATTATATCATTC
CTGATAATGCTATGTGAGTGTTTTTAATAAAATTTATATT
TATTTAATGCACTCTAA
PREDICTED:XM_006714242.2GTAGAGAAGCAGAAGGAAGCAAGATGGCTGCCCTTTAG
Homo sapiens
GATTTGTTAGAAAGGAGACCCGACTGCAACTG
tetCTGGATTGCTGCAAGGCTGAGGGACGAGAACGAGGCTG
methylcytosineGCAAACATTCAGCAGCACACCCTCTCAAGATT
dioxygenase 2GTTTACTTGCCTTTGCTCCTGTTGAGTTACAACGCTTGGA
(TET2),AGCAGGAGATGGGCTCAGCAGCAGCCAATA
transcriptGGACATGATCCAGGAAGAGCAGTAAGGGACTGAGCTGC
variant X2,TGAATTCAACTAGAGGGCAGCCTTGTGGATGG
mRNACCCCGAAGCAAGCCTGATGGAACAGGATAGAACCAACC
[SEQ ID NO:ATGTTGAGGGCAACAGACTAAGTCCATTCCTG
953]ATACCATCACCTCCCATTTGCCAGACAGAACCTCTGGCT
ACAAAGCTCCAGAATGGAAGCCCACTGCCTG
AGAGAGCTCATCCAGAAGTAAATGGAGACACCAAGTGG
CACTCTTTCAAAAGTTATTATGGAATACCCTG
TATGAAGGGAAGCCAGAATAGTCGTGTGAGTCCTGACTT
TACACAAGAAAGTAGAGGGTATTCCAAGTGT
TTGCAAAATGGAGGAATAAAACGCACAGTTAGTGAACCT
TCTCTCTCTGGGCTCCTTCAGATCAAGAAAT
TGAAACAAGACCAAAAGGCTAATGGAGAAAGACGTAAC
TTCGGGGTAAGCCAAGAAAGAAATCCAGGTGA
AAGCAGTCAACCAAATGTCTCCGATTTGAGTGATAAGAA
AGAATCTGTGAGTTCTGTAGCCCAAGAAAAT
GCAGTTAAAGATTTCACCAGTTTTTCAACACATAACTGC
AGTGGGCCTGAAAATCCAGAGCTTCAGATTC
TGAATGAGCAGGAGGGGAAAAGTGCTAATTACCATGAC
AAGAACATTGTATTACTTAAAAACAAGGCAGT
GCTAATGCCTAATGGTGCTACAGTTTCTGCCTCTTCCGTG
GAACACACACATGGTGAACTCCTGGAAAAA
ACACTGTCTCAATATTATCCAGATTGTGTTTCCATTGCGG
TGCAGAAAACCACATCTCACATAAATGCCA
TTAACAGTCAGGCTACTAATGAGTTGTCCTGTGAGATCA
CTCACCCATCGCATACCTCAGGGCAGATCAA
TTCCGCACAGACCTCTAACTCTGAGCTGCCTCCAAAGCC
AGCTGCAGTGGTGAGTGAGGCCTGTGATGCT
GATGATGCTGATAATGCCAGTAAACTAGCTGCAATGCTA
AATACCTGTTCCTTTCAGAAACCAGAACAAC
TACAACAACAAAAATCAGTTTTTGAGATATGCCCATCTC
CTGCAGAAAATAACATCCAGGGAACCACAAA
GCTAGCGTCTGGTGAAGAATTCTGTTCAGGTTCCAGCAG
CAATTTGCAAGCTCCTGGTGGCAGCTCTGAA
CGGTATTTAAAACAAAATGAAATGAATGGTGCTTACTTC
AAGCAAAGCTCAGTGTTCACTAAGGATTCCT
TTTCTGCCACTACCACACCACCACCACCATCACAATTGCT
TCTTTCTCCCCCTCCTCCTCTTCCACAGGT
TCCTCAGCTTCCTTCAGAAGGAAAAAGCACTCTGAATGG
TGGAGTTTTAGAAGAACACCACCACTACCCC
AACCAAAGTAACACAACACTTTTAAGGGAAGTGAAAAT
AGAGGGTAAACCTGAGGCACCACCTTCCCAGA
GTCCTAATCCATCTACACATGTATGCAGCCCTTCTCCGAT
GCTTTCTGAAAGGCCTCAGAATAATTGTGT
GAACAGGAATGACATACAGACTGCAGGGACAATGACTG
TTCCATTGTGTTCTGAGAAAACAAGACCAATG
TCAGAACACCTCAAGCATAACCCACCAATTTTTGGTAGC
AGTGGAGAGCTACAGGACAACTGCCAGCAGT
TGATGAGAAACAAAGAGCAAGAGATTCTGAAGGGTCGA
GACAAGGAGCAAACACGAGATCTTGTGCCCCC
AACACAGCACTATCTGAAACCAGGATGGATTGAATTGAA
GGCCCCTCGTTTTCACCAAGCGGAATCCCAT
CTAAAACGTAATGAGGCATCACTGCCATCAATTCTTCAG
TATCAACCCAATCTCTCCAATCAAATGACCT
CCAAACAATACACTGGAAATTCCAACATGCCTGGGGGGC
TCCCAAGGCAAGCTTACACCCAGAAAACAAC
ACAGCTGGAGCACAAGTCACAAATGTACCAAGTTGAAAT
GAATCAAGGGCAGTCCCAAGGTACAGTGGAC
CAACATCTCCAGTTCCAAAAACCCTCACACCAGGTGCAC
TTCTCCAAAACAGACCATTTACCAAAAGCTC
ATGTGCAGTCACTGTGTGGCACTAGATTTCATTTTCAACA
AAGAGCAGATTCCCAAACTGAAAAACTTAT
GTCCCCAGTGTTGAAACAGCACTTGAATCAACAGGCTTC
AGAGACTGAGCCATTTTCAAACTCACACCTT
TTGCAACATAAGCCTCATAAACAGGCAGCACAAACACA
ACCATCCCAGAGTTCACATCTCCCTCAAAACC
AGCAACAGCAGCAAAAATTACAAATAAAGAATAAAGAG
GAAATACTCCAGACTTTTCCTCACCCCCAAAG
CAACAATGATCAGCAAAGAGAAGGATCATTCTTTGGCCA
GACTAAAGTGGAAGAATGTTTTCATGGTGAA
AATCAGTATTCAAAATCAAGCGAGTTCGAGACTCATAAT
GTCCAAATGGGACTGGAGGAAGTACAGAATA
TAAATCGTAGAAATTCCCCTTATAGTCAGACCATGAAAT
CAAGTGCATGCAAAATACAGGTTTCTTGTTC
AAACAATACACACCTAGTTTCAGAGAATAAAGAACAGA
CTACACATCCTGAACTTTTTGCAGGAAACAAG
ACCCAAAACTTGCATCACATGCAATATTTTCCAAATAAT
GTGATCCCAAAGCAAGATCTTCTTCACAGGT
GCTTTCAAGAACAGGAGCAGAAGTCACAACAAGCTTCA
GTTCTACAGGGATATAAAAATAGAAACCAAGA
TATGTCTGGTCAACAAGCTGCGCAACTTGCTCAGCAAAG
GTACTTGATACATAACCATGCAAATGTTTTT
CCTGTGCCTGACCAGGGAGGAAGTCACACTCAGACCCCT
CCCCAGAAGGACACTCAAAAGCATGCTGCTC
TAAGGTGGCATCTCTTACAGAAGCAAGAACAGCAGCAA
ACACAGCAACCCCAAACTGAGTCTTGCCATAG
TCAGATGCACAGGCCAATTAAGGTGGAACCTGGATGCAA
GCCACATGCCTGTATGCACACAGCACCACCA
GAAAACAAAACATGGAAAAAGGTAACTAAGCAAGAGAA
TCCACCTGCAAGCTGTGATAATGTGCAGCAAA
AGAGCATCATTGAGACCATGGAGCAGCATCTGAAGCAGT
TTCACGCCAAGTCGTTATTTGACCATAAGGC
TCTTACTCTCAAATCACAGAAGCAAGTAAAAGTTGAAAT
GTCAGGGCCAGTCACAGTTTTGACTAGACAA
ACCACTGCTGCAGAACTTGATAGCCACACCCCAGCTTTA
GAGCAGCAAACAACTTCTTCAGAAAAGACAC
CAACCAAAAGAACAGCTGCTTCTGTTCTCAATAATTTTAT
AGAGTCACCTTCCAAATTACTAGATACTCC
TATAAAAAATTTATTGGATACACCTGTCAAGACTCAATA
TGATTTCCCATCTTGCAGATGTGTAGGTTTG
GACAGAAGGGTAAAGCTATTAGGATTGAAAGAGTCATCT
ATACTGGTAAAGAAGGCAAAAGTTCTCAGGG
ATGTCCTATTGCTAAGTGGGAGAACTTGCGCCTGTCAGG
GGCTGGATCCAGAAACCTGTGGTGCCTCCTT
CTCTTTTGGTTGTTCATGGAGCATGTACTACAATGGATGT
AAGTTTGCCAGAAGCAAGATCCCAAGGAAG
TTTAAGCTGCTTGGGGATGACCCAAAAGAGGAAGAGAA
ACTGGAGTCTCATTTGCAAAACCTGTCCACTC
TTATGGCACCAACATATAAGAAACTTGCACCTGATGCAT
ATAATAATCAGATTGAATATGAACACAGAGC
ACCAGAGTGCCGTCTGGGTCTGAAGGAAGGCCGTCCATT
CTCAGGGGTCACTGCATGTTTGGACTTCTGT
GCTCATGCCCACAGAGACTTGCACAACATGCAGAATGGC
AGCACATTGGTATGCACTCTCACTAGAGAAG
ACAATCGAGAATTTGGAGGAAAACCTGAGGATGAGCAG
CTTCACGTTCTGCCTTTATACAAAGTCTCTGA
CGTGGATGAGTTTGGGAGTGTGGAAGCTCAGGAGGAGA
AAAAACGGAGTGGTGCCATTCAGGTACTGAGT
TCTTTTCGGCGAAAAGTCAGGATGTTAGCAGAGCCAGTC
AAGACTTGCCGACAAAGGAAACTAGAAGCCA
AGAAAGCTGCAGCTGAAAAGCTTTCCTCCCTGGAGAACA
GCTCAAATAAAAATGAAAAGGAAAAGTCAGC
CCCATCACGTACAAAACAAACTGAAAACGCAAGCCAGG
CTAAACAGTTGGCAGAACTTTTGCGACTTTCA
GGACCAGTCATGCAGCAGTCCCAGCAGCCCCAGCCTCTA
CAGAAGCAGCCACCACAGCCCCAGCAGCAGC
AGAGACCCCAGCAGCAGCAGCCACATCACCCTCAGACA
GAGTCTGTCAACTCTTATTCTGCTTCTGGATC
CACCAATCCATACATGAGACGGCCCAATCCAGTTAGTCC
TTATCCAAACTCTTCACACACTTCAGATATC
TATGGAAGCACCAGCCCTATGAACTTCTATTCCACCTCAT
CTCAAGCTGCAGGTTCATATTTGAATTCTT
CTAATCCCATGAACCCTTACCCTGGGCTTTTGAATCAGA
ATACCCAATATCCATCATATCAATGCAATGG
AAACCTATCAGTGGACAACTGCTCCCCATATCTGGGTTC
CTATTCTCCCCAGTCTCAGCCGATGGATCTG
TATAGGTATCCAAGCCAAGACCCTCTGTCTAAGCTCAGT
CTACCACCCATCCATACACTTTACCAGCCAA
GGTTTGGAAATAGCCAGAGTTTTACATCTAAATACTTAG
GTTATGGAAACCAAAATATGCAGGGAGATGG
TTTCAGCAGTTGTACCATTAGACCAAATGTACATCATGT
AGGGAAATTGCCTCCTTATCCCACTCATGAG
ATGGATGGCCACTTCATGGGAGCCACCTCTAGATTACCA
CCCAATCTGAGCAATCCAAACATGGACTATA
AAAATGGTGAACATCATTCACCTTCTCACATAATCCATA
ACTACAGTGCAGCTCCGGGCATGTTCAACAG
CTCTCTTCATGCCCTGCATCTCCAAAACAAGGAGAATGA
CATGCTTTCCCACACAGCTAATGGGTTATCA
AAGATGCTTCCAGCTCTTAACCATGATAGAACTGCTTGT
GTCCAAGGAGGCTTACACAAATTAAGTGATG
CTAATGGTCAGGAAAAGCAGCCATTGGCACTAGTCCAGG
GTGTGGCTTCTGGTGCAGAGGACAACGATGA
GGTCTGGTCAGACAGCGAGCAGAGCTTTCTGGATCCTGA
CATTGGGGGAGTGGCCGTGGCTCCAACTCAT
GGGTCAATTCTCATTGAGTGTGCAAAGCGTGAGCTGCAT
GCCACAACCCCTTTAAAGAATCCCAATAGGA
ATCACCCCACCAGGATCTCCCTCGTCTTTTACCAGCATAA
GAGCATGAATGAGCCAAAACATGGCTTGGC
TCTTTGGGAAGCCAAAATGGCTGAAAAAGCCCGTGAGA
AAGAGGAAGAGTGTGAAAAGTATGGCCCAGAC
TATGTGCCTCAGAAATCCCATGGCAAAAAAGTGAAACGG
GAGCCTGCTGAGCCACATGAAACTTCAGAGC
CCACTTACCTGCGTTTCATCAAGTCTCTTGCCGAAAGGAC
CATGTCCGTGACCACAGACTCCACAGTAAC
TACATCTCCATATGCCTTCACTCGGGTCACAGGGCCTTAC
AACAGATATATATGATATCACCCCCTTTTG
TTGGTTACCTCACTTGAAAAGACCACAACCAACCTGTCA
GTAGTATAGTTCTCATGACGTGGGCAGTGGG
GAAAGGTCACAGTATTCATGACAAATGTGGTGGGAAAA
ACCTCAGCTCACCAGCAACAAAAGAGGTTATC
TTACCATAGCACTTAATTTTCACTGGCTCCCAAGTGGTCA
CAGATGGCATCTAGGAAAAGACCAAAGCAT
TCTATGCAAAAAGAAGGTGGGGAAGAAAGTGTTCCGCA
ATTTACATTTTTAAACACTGGTTCTATTATTG
GACGAGATGATATGTAAATGTGATCCCCCCCCCCCGCTT
ACAACTCTACACATCTGTGACCACTTTTAAT
AATATCAAGTTTGCATAGTCATGGAACACAAATCAAACA
AGTACTGTAGTATTACAGTGACAGGAATCTT
AAAATACCATCTGGTGCTGAATATATGATGTACTGAAAT
ACTGGAATTATGGCTTTTTGAAATGCAGTTT
TTACTGTAATCTTAACTTTTATTTATCAAAATAGCTACAG
GAAACATGAATAGCAGGAAAACACTGAATT
TGTTTGGATGTTCTAAGAAATGGTGCTAAGAAAATGGTG
TCTTTAATAGCTAAAAATTTAATGCCTTTAT
ATCATCAAGATGCTATCAGTGTACTCCAGTGCCCTTGAA
TAATAGGGGTACCTTTTCATTCAAGTTTTTA
TCATAATTACCTATTCTTACACAAGCTTAGTTTTTAAAAT
GTGGACATTTTAAAGGCCTCTGGATTTTGC
TCATCCAGTGAAGTCCTTGTAGGACAATAAACGTATATA
TGTACATATATACACAAACATGTATATGTGC
ACACACATGTATATGTATAAATATTTTAAATGGTGTTTTA
GAAGCACTTTGTCTACCTAAGCTTTGACAA
CTTGAACAATGCTAAGGTACTGAGATGTTTAAAAAACAA
GTTTACTTTCATTTTAGAATGCAAAGTTGAT
TTTTTTAAGGAAACAAAGAAAGCTTTTAAAATATTTTTGC
TTTTAGCCATGCATCTGCTGATGAGCAATT
GTGTCCATTTTTAACACAGCCAGTTAAATCCACCATGGG
GCTTACTGGATTCAAGGGAATACGTTAGTCC
ACAAAACATGTTTTCTGGTGCTCATCTCACATGCTATACT
GTAAAACAGTTTTATACAAAATTGTATGAC
AAGTTCATTGCTCAAAAATGTACAGTTTTAAGAATTTTCT
ATTAACTGCAGGTAATAATTAGCTGCATGC
TGCAGACTCAACAAAGCTAGTTCACTGAAGCCTATGCTA
TTTTATGGATCATAGGCTCTTCAGAGAACTG
AATGGCAGTCTGCCTTTGTGTTGATAATTATGTACATTGT
GACGTTGTCATTTCTTAGCTTAAGTGTCCT
CTTTAACAAGAGGATTGAGCAGACTGATGCCTGCATAAG
ATGAATAAACAGGGTTAGTTCCATGTGAATC
TGTCAGTTAAAAAGAAACAAAAACAGGCAGCTGGTTTGC
TGTGGTGGTTTTAAATCATTAATTTGTATAA
AGAAGTGAAAGAGTTGTATAGTAAATTAAATTGTAAACA
AAACTTTTTTAATGCAATGCTTTAGTATTTT
AGTACTGTAAAAAAATTAAATATATACATATATATATAT
ATATATATATATATATATATGAGTTTGAAGC
AGAATTCACATCATGATGGTGCTACTCAGCCTGCTACAA
ATATATCATAATGTGAGCTAAGAATTCATTA
AATGTTTGAGTGATGTTCCTACTTGTCATATACCTCAACA
CTAGTTTGGCAATAGGATATTGAACTGAGA
GTGAAAGCATTGTGTACCATCATTTTTTTCCAAGTCCTTT
TTTTTATTGTTAAAAAAAAAAGCATACCTT
TTTTCAATACTTGATTTCTTAGCAAGTATAACTTGAACTT
CAACCTTTTTGTTCTAAAAATTCAGGGATA
TTTCAGCTCATGCTCTCCCTATGCCAACATGTCACCTGTG
TTTATGTAAAATTGTTGTAGGTTAATAAAT
ATATTCTTTGTCAGGGATTTAACCCTTTTATTTTGAATCC
CTTCTATTTTACTTGTACATGTGCTGATGT
AACTAAAACTAATTTTGTAAATCTGTTGGCTCTTTTTATT
GTAAAGAAAAGCATTTTAAAAGTTTGAGGA
ATCTTTTGACTGTTTCAAGCAGGAAAAAAAAATTACATG
AAAATAGAATGCACTGAGTTGATAAAGGGAA
AAATTGTAAGGCAGGAGTTTGGCAAGTGGCTGTTGGCCA
GAGACTTACTTGTAACTCTCTAAATGAAGTT
TTTTTGATCCTGTAATCACTGAAGGTACATACTCCATGTG
GACTTCCCTTAAACAGGCAAACACCTACAG
GTATGGTGTGCAACAGATTGTACAATTACATTTTGGCCT
AAATACATTTTTGCTTACTAGTATTTAAAAT
AAATTCTTAATCAGAGGAGGCCTTTGGGTTTTATTGGTCA
AATCTTTGTAAGCTGGCTTTTGTCTTTTTA
AAAAATTTCTTGAATTTGTGGTTGTGTCCAATTTGCAAAC
ATTTCCAAAAATGTTTGCTTTGCTTACAAA
CCACATGATTTTAATGTTTTTTGTATACCATAATATCTAG
CCCCAAACATTTGATTACTACATGTGCATT
GGTGATTTTGATCATCCATTCTTAATATTTGATTTCTGTG
TCACCTACTGTCATTTGTTAAACTGCTGGC
CAACAAGAACAGGAAGTATAGTTTGGGGGGTTGGGGAG
AGTTTACATAAGGAAGAGAAGAAATTGAGTGG
CATATTGTAAATATCAGATCTATAATTGTAAATATAAAA
CCTGCCTCAGTTAGAATGAATGGAAAGCAGA
TCTACAATTTGCTAATATAGGAATATCAGGTTGACTATAT
AGCCATACTTGAAAATGCTTCTGAGTGGTG
TCAACTTTACTTGAATGAATTTTTCATCTTGATTGACGCA
CAGTGATGTACAGTTCACTTCTGAAGCTAG
TGGTTAACTTGTGTAGGAAACTTTTGCAGTTTGACACTAA
GATAACTTCTGTGTGCATTTTTCTATGCTT
TTTTAAAAACTAGTTTCATTTCATTTTCATGAGATGTTTG
GTTTATAAGATCTGAGGATGGTTATAAATA
CTGTAAGTATTGTAATGTTATGAATGCAGGTTATTTGAA
AGCTGTTTATTATTATATCATTCCTGATAAT
GCTATGTGAGTGTTTTTAATAAAATTTATATTTATTTAAT
GCACTCTAA
Homo sapiens
NM_017628.4AAACAGAAGGTGGGCCGGGGCGGGGAGAAACAGAACTC
tetGGTCAATTTCCCAGTTTGTCGGGTCTTTAAAA
methylcytosineATACAGGCCCCTAAAGCACTAAGGGCATGCCCTCGGTGA
dioxygenase 2AACAGGGGAGCGCTTCTGCTGAATGAGATTA
(TET2),AAGCGACAGAAAAGGGAAAGGAGAGCGCGGGCAACGG
transcriptGATCTAAAGGGAGATAGAGACGCGGGCCTCTGA
variant 2,GGGCTGGCAAACATTCAGCAGCACACCCTCTCAAGATTG
mRNATTTACTTGCCTTTGCTCCTGTTGAGTTACAA
[SEQ ID NO:CGCTTGGAAGCAGGAGATGGGCTCAGCAGCAGCCAATA
954]GGACATGATCCAGGAAGAGCAGTAAGGGACTG
AGCTGCTGAATTCAACTAGAGGGCAGCCTTGTGGATGGC
CCCGAAGCAAGCCTGATGGAACAGGATAGAA
CCAACCATGTTGAGGGCAACAGACTAAGTCCATTCCTGA
TACCATCACCTCCCATTTGCCAGACAGAACC
TCTGGCTACAAAGCTCCAGAATGGAAGCCCACTGCCTGA
GAGAGCTCATCCAGAAGTAAATGGAGACACC
AAGTGGCACTCTTTCAAAAGTTATTATGGAATACCCTGT
ATGAAGGGAAGCCAGAATAGTCGTGTGAGTC
CTGACTTTACACAAGAAAGTAGAGGGTATTCCAAGTGTT
TGCAAAATGGAGGAATAAAACGCACAGTTAG
TGAACCTTCTCTCTCTGGGCTCCTTCAGATCAAGAAATTG
AAACAAGACCAAAAGGCTAATGGAGAAAGA
CGTAACTTCGGGGTAAGCCAAGAAAGAAATCCAGGTGA
AAGCAGTCAACCAAATGTCTCCGATTTGAGTG
ATAAGAAAGAATCTGTGAGTTCTGTAGCCCAAGAAAATG
CAGTTAAAGATTTCACCAGTTTTTCAACACA
TAACTGCAGTGGGCCTGAAAATCCAGAGCTTCAGATTCT
GAATGAGCAGGAGGGGAAAAGTGCTAATTAC
CATGACAAGAACATTGTATTACTTAAAAACAAGGCAGTG
CTAATGCCTAATGGTGCTACAGTTTCTGCCT
CTTCCGTGGAACACACACATGGTGAACTCCTGGAAAAAA
CACTGTCTCAATATTATCCAGATTGTGTTTC
CATTGCGGTGCAGAAAACCACATCTCACATAAATGCCAT
TAACAGTCAGGCTACTAATGAGTTGTCCTGT
GAGATCACTCACCCATCGCATACCTCAGGGCAGATCAAT
TCCGCACAGACCTCTAACTCTGAGCTGCCTC
CAAAGCCAGCTGCAGTGGTGAGTGAGGCCTGTGATGCTG
ATGATGCTGATAATGCCAGTAAACTAGCTGC
AATGCTAAATACCTGTTCCTTTCAGAAACCAGAACAACT
ACAACAACAAAAATCAGTTTTTGAGATATGC
CCATCTCCTGCAGAAAATAACATCCAGGGAACCACAAAG
CTAGCGTCTGGTGAAGAATTCTGTTCAGGTT
CCAGCAGCAATTTGCAAGCTCCTGGTGGCAGCTCTGAAC
GGTATTTAAAACAAAATGAAATGAATGGTGC
TTACTTCAAGCAAAGCTCAGTGTTCACTAAGGATTCCTTT
TCTGCCACTACCACACCACCACCACCATCA
CAATTGCTTCTTTCTCCCCCTCCTCCTCTTCCACAGGTTCC
TCAGCTTCCTTCAGAAGGAAAAAGCACTC
TGAATGGTGGAGTTTTAGAAGAACACCACCACTACCCCA
ACCAAAGTAACACAACACTTTTAAGGGAAGT
GAAAATAGAGGGTAAACCTGAGGCACCACCTTCCCAGA
GTCCTAATCCATCTACACATGTATGCAGCCCT
TCTCCGATGCTTTCTGAAAGGCCTCAGAATAATTGTGTG
AACAGGAATGACATACAGACTGCAGGGACAA
TGACTGTTCCATTGTGTTCTGAGAAAACAAGACCAATGT
CAGAACACCTCAAGCATAACCCACCAATTTT
TGGTAGCAGTGGAGAGCTACAGGACAACTGCCAGCAGTT
GATGAGAAACAAAGAGCAAGAGATTCTGAAG
GGTCGAGACAAGGAGCAAACACGAGATCTTGTGCCCCC
AACACAGCACTATCTGAAACCAGGATGGATTG
AATTGAAGGCCCCTCGTTTTCACCAAGCGGAATCCCATC
TAAAACGTAATGAGGCATCACTGCCATCAAT
TCTTCAGTATCAACCCAATCTCTCCAATCAAATGACCTCC
AAACAATACACTGGAAATTCCAACATGCCT
GGGGGGCTCCCAAGGCAAGCTTACACCCAGAAAACAAC
ACAGCTGGAGCACAAGTCACAAATGTACCAAG
TTGAAATGAATCAAGGGCAGTCCCAAGGTACAGTGGACC
AACATCTCCAGTTCCAAAAACCCTCACACCA
GGTGCACTTCTCCAAAACAGACCATTTACCAAAAGCTCA
TGTGCAGTCACTGTGTGGCACTAGATTTCAT
TTTCAACAAAGAGCAGATTCCCAAACTGAAAAACTTATG
TCCCCAGTGTTGAAACAGCACTTGAATCAAC
AGGCTTCAGAGACTGAGCCATTTTCAAACTCACACCTTTT
GCAACATAAGCCTCATAAACAGGCAGCACA
AACACAACCATCCCAGAGTTCACATCTCCCTCAAAACCA
GCAACAGCAGCAAAAATTACAAATAAAGAAT
AAAGAGGAAATACTCCAGACTTTTCCTCACCCCCAAAGC
AACAATGATCAGCAAAGAGAAGGATCATTCT
TTGGCCAGACTAAAGTGGAAGAATGTTTTCATGGTGAAA
ATCAGTATTCAAAATCAAGCGAGTTCGAGAC
TCATAATGTCCAAATGGGACTGGAGGAAGTACAGAATAT
AAATCGTAGAAATTCCCCTTATAGTCAGACC
ATGAAATCAAGTGCATGCAAAATACAGGTTTCTTGTTCA
AACAATACACACCTAGTTTCAGAGAATAAAG
AACAGACTACACATCCTGAACTTTTTGCAGGAAACAAGA
CCCAAAACTTGCATCACATGCAATATTTTCC
AAATAATGTGATCCCAAAGCAAGATCTTCTTCACAGGTG
CTTTCAAGAACAGGAGCAGAAGTCACAACAA
GCTTCAGTTCTACAGGGATATAAAAATAGAAACCAAGAT
ATGTCTGGTCAACAAGCTGCGCAACTTGCTC
AGCAAAGGTACTTGATACATAACCATGCAAATGTTTTTC
CTGTGCCTGACCAGGGAGGAAGTCACACTCA
GACCCCTCCCCAGAAGGACACTCAAAAGCATGCTGCTCT
AAGGTGGCATCTCTTACAGAAGCAAGAACAG
CAGCAAACACAGCAACCCCAAACTGAGTCTTGCCATAGT
CAGATGCACAGGCCAATTAAGGTGGAACCTG
GATGCAAGCCACATGCCTGTATGCACACAGCACCACCAG
AAAACAAAACATGGAAAAAGGTAACTAAGCA
AGAGAATCCACCTGCAAGCTGTGATAATGTGCAGCAAAA
GAGCATCATTGAGACCATGGAGCAGCATCTG
AAGCAGTTTCACGCCAAGTCGTTATTTGACCATAAGGCT
CTTACTCTCAAATCACAGAAGCAAGTAAAAG
TTGAAATGTCAGGGCCAGTCACAGTTTTGACTAGACAAA
CCACTGCTGCAGAACTTGATAGCCACACCCC
AGCTTTAGAGCAGCAAACAACTTCTTCAGAAAAGACACC
AACCAAAAGAACAGCTGCTTCTGTTCTCAAT
AATTTTATAGAGTCACCTTCCAAATTACTAGATACTCCTA
TAAAAAATTTATTGGATACACCTGTCAAGA
CTCAATATGATTTCCCATCTTGCAGATGTGTAGGTAAGTG
CCAGAAATGTACTGAGACACATGGCGTTTA
TCCAGAATTAGCAAATTTATCTTCAGATATGGGATTTTCC
TTCTTTTTTTAAATCTTGAGTCTGGCAGCA
ATTTGTAAAGGCTCATAAAAATCTGAAGCTTACATTTTTT
GTCAAGTTACCGATGCTTGTGTCTTGTGAA
AGAGAACTTCACTTACATGCAGTTTTTCCAAAAGAATTA
AATAATCGTGCATGTTTATTTTTCCCTCTCT
TCAGATCCTGTAAAATTTGAATGTATCTGTTTTAGATCAA
TTCGCCTATTTAGCTCTTTGTATATTATCT
CCTGGAGAGACAGCTAGGCAGCAAAAAAACAATCTATT
AAAATGAGAAAATAACGACCATAGGCAGTCTA
ATGTACGAACTTTAAATATTTTTTAATTCAAGGTAAAATA
TATTAGTTTCACAAGATTTCTGGCTAATAG
GGAAATTATTATCTTCAGTCTTCATGAGTTGGGGGAAAT
GATAATGCTGACACTCTTAGTGCTCCTAAAG
TTTCCTTTTCTCCATTTATACATTTGGAATGTTGTGATTTA
TATTCATTTTGATTCCCTTTTCTCTAAAA
TTTCATCTTTTTGATTAAAAAATATGATACAGGCATACCT
CAGAGATATTGTGGGTTTGGCTCCATACCA
CAATAAAATGAATATTACAATAAAGCAAGTTGTAAGGAC
TTTTTGGTTTCTCACTGTATGTAAAAGTTAT
TTATATACTATACTGTAACATACTAAGTGTGCAATAGCA
TTGTGTCTAAAAAATATATACTTTAAAAATA
ATTTATTGTTAAAAAAATGCCAACAATTATCTGGGCCTTT
AGTGAGTGCTAATCTTTTTGCTGGTGGAGG
GTCGTGCTTCAGTATTGATCGCTGTGGACTGATCATGGTG
GTAGTTGCTGAAGGTTGCTGGGATGGCTGT
GTGTGTGGCAATTTCTTAAAATAAGACAACAGTGAAGTG
CTGTATCAATTGATTTTTCCATTCACAAAAG
ATTTCTCTGTAGCATGCAATGCTGTTTGATAGCATTTAAC
CCACAGCAGAATTTCTTTGAAAATTGGACT
CAGTCCTCTCAAACTGTGCTGCTGCTTTATCAACTAAGTT
TTTGTAATTTTCTGAATCCTTTGTTGTCAT
TTCAGCAGTTTACAGCATCTTCATTGGAAGTATATTCCAT
CTCAAACATTCTTTGTTCATCCATAAGAAG
CAACTTCTTATCAAGTTTTTTCATGACATTGCAGTAACTC
AGCCCCATCTTCAGGCTCTACTTCTAATTC
TGGTTCTCTTGCTACATCTCCCTCATCTGCAGTGACCTCT
CCACGGAAGTCTTGAACTCCTCAAAGTAAT
CCATGAGGGTTGGAATCAACTTCTAAACTCCTGTTAATG
TTGATATATTGACCCCCTCCCATGAATTATG
AATGTTCTTAATAACTTCTAAATGGTGATACCTTTCCAGA
AGGCTTTCAATGTACTTTGCCCGGATCCAT
CAGAAGACTATCTTGGCAGCTGTAGACTAACAATATATT
TCTTAAATGATAAGACTTGAAAGTCAAAAGT
ACTCCTTAATCCATAGGCTGCAGAATCAATGTTGTATTA
ACAGGCACGAAAACAGCATTAATCTTGTGCA
TCTCCATCGGAGCTCTTGGGTGACTAGGTGCCTTGAGCA
GTAATATTTTGAAAGGAGGTTTTGGTTTTGT
TTTTTGTTTTTTTTTTTTGTTTTTTAGCAGTAAGTCTCAAC
ACTGGGCTTAAAATATTCAGTAAACTATG
TTGTAAAAAGATGTGTTATCATCCAGACTTTGTTGTTCCA
TTACTCTACACAAGCAGGGTACACTTAGCA
TAATTCTTAAGGGCCTTGGAATTTTCAGAATGGTAAATG
AGTATGGGCTTCAACTTAAAATCATCAACTG
CATTAGCCTGTAACAAGAGAGTCAGCCTGTCCTTTGAAG
CAAGGCATTGACTTCTATCTATGAAAGTCTT
AGATGGCACCTTGTTTCAATAGTAGGCTGTTTAGTACAG
CCACCTTCATCAGTGATCTTAGCTAGATCTT
CTGCATAACTTGCTGCAGCTTCTACATCAGCACTTGCTGC
CTCACCTTGTCCTTTTATGTTATAGAGACA
GCTGCGCTTCTTAAACTTTATAAACCAACTTCTGCTAGCT
TCCAACTTCTCTTCTGCAGCTTCCTCATTC
TCTTCATAGAACTGAAGGGAGTCAAGGCCTTGCTCTGGA
TTAAGCTTTGGCTTAAGGAATGTTGTGGCTG
ACGTGATCTTCTATCCAGACCACTAAAGCGCTCTCCATAT
CAGCAATAAGGCCGTTTTGCTTTCTTACCT
TTCATGTGTTCACTGGAGTAATTTCCTTCAAGAATTTTTC
CTTTACATTCACAACTTGGCTAACTGGCAT
GCAAGGCCTAGCTTTCAGCCTGTCTTGGCTTTTGACATGC
CTTCCTCACTTAGCTCGTCATATCTAGCTT
TTGATTTAAAGTGGCAGGCATACAACTCTTCCTTTCACTT
GAACACTTAGAGGCCACTGTAGGGTTATTA
ATTGGCCTAATTTCAATATTGTTGTGTTTTAGGGAATAGA
GAGGCCCAGGGAGAGGGAGAGAGCCCAAAC
GGCTGGTTGATAGAGCAGGCAGAATGCACACAACATTTA
TCAGATTATGTTTGCACCATTTACCAGATTA
TGGGTACGGTTTGTGGCACCCCCCAAAAATTAGAATAGT
AACATCAAAGATCACTGATCACAGATCGCCA
TAACATAAATAATAATAAACTTTAAAATACTGTGAGAAT
TACCAAAATGTGATACAGAGACATGAAGTGA
GCACATGCTGTTGAAAAAAATGACACTGATAGACATACT
TAACACGTGGGATTGCCACAAACCTTCAGTT
TGTAAAAGTCACAGTAACTGTGACTCACAAAAGAACAA
AGCACAATAAAACGAGGTATGCCTGTATTTTT
AAAAAAAGCTTTTTGTTAAAATTCAGGATATGTAATAGG
TCTGTAGGAATAGTGAAATATTTTTGCTGAT
GGATGTAGATATATACGTGGATAGAGATGAAGATCTTAA
TTATAGCTATGCAGCATAGATTTAGTCAAAG
ACATTTGAAAAGACAAATGTTAAATTAGTGTGGCTAATG
ACCTACCCGTGCCATGTTTTCCCTCTTGCAA
TGAGATACCCCACACTGTGTAGAAGGATGGAGGGAGGA
CTCCTACTGTCCCTCTTTGCGTGTGGTTATTA
AGTTGCCTCACTGGGCTAAAACACCACACATCTCATAGA
TAATATTTGGTAAGTTGTAATCGTCTTCACT
CTTCTCTTATCACCCACCCCTATCTTCCCACTTTTCCATCT
TTGTTGGTTTGCAACAGCCCCTTCTTTTT
GCCTGACTCTCCAGGATTTTCTCTCATCATAAATTGTTCT
AAAGTACATACTAATATGGGTCTGGATTGA
CTATTCTTATTTGCAAAACAGCAATTAAATGTTATAGGG
AAGTAGGAAGAAAAAGGGGTATCCTTGACAA
TAAACCAAGCAATATTCTGGGGGTGGGATAGAGCAGGA
AATTTTATTTTTAATCTTTTAAAATCCAAGTA
ATAGGTAGGCTTCCAGTTAGCTTTAAATGTTTTTTTTTTC
CAGCTCAAAAAATTGGATTGTAGTTGATAC
TACATATAATACATTCTAATTCCCTCACTGTATTCTTTGT
TTAGTTTCATTTATTTGGTTTAAAATAATT
TTTTATCCCATATCTGAAATGTAATATATTTTTATCCAAC
AACCAGCATGTACATATACTTAATTATGTG
GCACATTTTCTAATAGATCAGTCCATCAATCTACTCATTT
TAAAGAAAAAAAAATTTTAAAGTCACTTTT
AGAGCCCTTAATGTGTAGTTGGGGGTTAAGCTTTGTGGA
TGTAGCCTTTATATTTAGTATAATTGAGGTC
TAAAATAATAATCTTCTATTATCTCAACAGAGCAAATTA
TTGAAAAAGATGAAGGTCCTTTTTATACCCA
TCTAGGAGCAGGTCCTAATGTGGCAGCTATTAGAGAAAT
CATGGAAGAAAGGTAATTAACGCAAAGGCAC
AGGGCAGATTAACGTTTATCCTTTTGTATATGTCAGAATT
TTTCCAGCCTTCACACACAAAGCAGTAAAC
AATTGTAAATTGAGTAATTATTAGTAGGCTTAGCTATTCT
AGGGTTGCCAACACTACACACTGTGCTATT
CACCAGAGAGTCACAATATTTGACAGGACTAATAGTCTG
CTAGCTGGCACAGGCTGCCCACTTTGCGATG
GATGCCAGAAAACCCAGGCATGAACAGGAATCGGCCAG
CCAGGCTGCCAGCCACAAGGTACTGGCACAGG
CTCCAACGAGAGGTCCCACTCTGGCTTTCCCACCTGATA
ATAAAGTGTCAAAGCAGAAAGACTGGTAAAG
TGTGGTATAAGAAAAGAACCACTGAATTAAATTCACCTA
GTGTTGCAAATGAGTACTTATCTCTAAGTTT
TCTTTTACCATAAAAAGAGAGCAAGTGTGATATGTTGAA
TAGAAAGAGAAACATACTATTTACAGCTGCC
TTTTTTTTTTTTTTTCGCTATCAATCACAGGTATACAAGTA
CTTGCCTTTACTCCTGCATGTAGAAGACT
CTTATGAGCGAGATAATGCAGAGAAGGCCTTTCATATAA
ATTTATACAGCTCTGAGCTGTTCTTCTTCTA
GGGTGCCTTTTCATTAAGAGGTAGGCAGTATTATTATTA
AAGTACTTAGGATACATTGGGGCAGCTAGGA
CATATTCAGTATCATTCTTGCTCCATTTCCAAATTATTCA
TTTCTAAATTAGCATGTAGAAGTTCACTAA
ATAATCATCTAGTGGCCTGGCAGAAATAGTGAATTTCCC
TAAGTGCCTTTTTTTTGTTGTTTTTTTGTTT
TGTTTTTTAAACAAGCAGTAGGTGGTGCTTTGGTCATAA
GGGAAGATATAGTCTATTTCTAGGACTATTC
CATATTTTCCATGTGGCTGGATACTAACTATTTGCCAGCC
TCCTTTTCTAAATTGTGAGACATTCTTGGA
GGAACAGTTCTAACTAAAATCTATTATGACTCCCCAAGT
TTTAAAATAGCTAAATTTAGTAAGGGAAAAA
ATAGTTTATGTTTTAGAAGACTGAACTTAGCAAACTAAC
CTGAATTTTGTGCTTTGTGAAATTTTATATC
GAAATGAGCTTTCCCATTTTCACCCACATGTAATTTACAA
AATAGTTCATTACAATTATCTGTACATTTT
GATATTGAGGAAAAACAAGGCTTAAAAACCATTATCCAG
TTTGCTTGGCGTAGACCTGTTTAAAAAATAA
TAAACCGTTCATTTCTCAGGATGTGGTCATAGAATAAAG
TTATGCTCAAATGTTCAAATATTTAAA
PREDICTED:XM_011532044.1TCAGGCTCTACTTCTAATTCTGGTTCTCTTGCTACATCTC
Homo sapiens
CCTCATCTGCAGTGACCTCTCCACGGAAGT
tetCTTGAACTCCTCAAAAGCAAATTATTGAAAAAGATGAAG
methylcytosineGTCCTTTTTATACCCATCTAGGAGCAGGTCC
dioxygenase 2TAATGTGGCAGCTATTAGAGAAATCATGGAAGAAAGGTT
(TET2),TGGACAGAAGGGTAAAGCTATTAGGATTGAA
transcriptAGAGTCATCTATACTGGTAAAGAAGGCAAAAGTTCTCAG
variant X9,GGATGTCCTATTGCTAAGTGGGTGGTTCGCA
mRNAGAAGCAGCAGTGAAGAGAAGCTACTGTGTTTGGTGCGG
[SEQ ID NO:GAGCGAGCTGGCCACACCTGTGAGGCTGCAGT
955]GATTGTGATTCTCATCCTGGTGTGGGAAGGAATCCCGCT
GTCTCTGGCTGACAAACTCTACTCGGAGCTT
ACCGAGACGCTGAGGAAATACGGCACGCTCACCAATCG
CCGGTGTGCCTTGAATGAAGAGAGAACTTGCG
CCTGTCAGGGGCTGGATCCAGAAACCTGTGGTGCCTCCT
TCTCTTTTGGTTGTTCATGGAGCATGTACTA
CAATGGATGTAAGTTTGCCAGAAGCAAGATCCCAAGGA
AGTTTAAGCTGCTTGGGGATGACCCAAAAGAG
GAAGAGAAACTGGAGTCTCATTTGCAAAACCTGTCCACT
CTTATGGCACCAACATATAAGAAACTTGCAC
CTGATGCATATAATAATCAGATTGAATATGAACACAGAG
CACCAGAGTGCCGTCTGGGTCTGAAGGAAGG
CCGTCCATTCTCAGGGGTCACTGCATGTTTGGACTTCTGT
GCTCATGCCCACAGAGACTTGCACAACATG
CAGAATGGCAGCACATTGGTATGCACTCTCACTAGAGAA
GACAATCGAGAATTTGGAGGAAAACCTGAGG
ATGAGCAGCTTCACGTTCTGCCTTTATACAAAGTCTCTGA
CGTGGATGAGTTTGGGAGTGTGGAAGCTCA
GGAGGAGAAAAAACGGAGTGGTGCCATTCAGGTACTGA
GTTCTTTTCGGCGAAAAGTCAGGATGTTAGCA
GAGCCAGTCAAGACTTGCCGACAAAGGAAACTAGAAGC
CAAGAAAGCTGCAGCTGAAAAGCTTTCCTCCC
TGGAGAACAGCTCAAATAAAAATGAAAAGGAAAAGTCA
GCCCCATCACGTACAAAACAAACTGAAAACGC
AAGCCAGGCTAAACAGTTGGCAGAACTTTTGCGACTTTC
AGGACCAGTCATGCAGCAGTCCCAGCAGCCC
CAGCCTCTACAGAAGCAGCCACCACAGCCCCAGCAGCA
GCAGAGACCCCAGCAGCAGCAGCCACATCACC
CTCAGACAGAGTCTGTCAACTCTTATTCTGCTTCTGGATC
CACCAATCCATACATGAGACGGCCCAATCC
AGTTAGTCCTTATCCAAACTCTTCACACACTTCAGATATC
TATGGAAGCACCAGCCCTATGAACTTCTAT
TCCACCTCATCTCAAGCTGCAGGTTCATATTTGAATTCTT
CTAATCCCATGAACCCTTACCCTGGGCTTT
TGAATCAGAATACCCAATATCCATCATATCAATGCAATG
GAAACCTATCAGTGGACAACTGCTCCCCATA
TCTGGGTTCCTATTCTCCCCAGTCTCAGCCGATGGATCTG
TATAGGTATCCAAGCCAAGACCCTCTGTCT
AAGCTCAGTCTACCACCCATCCATACACTTTACCAGCCA
AGGTTTGGAAATAGCCAGAGTTTTACATCTA
AATACTTAGGTTATGGAAACCAAAATATGCAGGGAGATG
GTTTCAGCAGTTGTACCATTAGACCAAATGT
ACATCATGTAGGGAAATTGCCTCCTTATCCCACTCATGA
GATGGATGGCCACTTCATGGGAGCCACCTCT
AGATTACCACCCAATCTGAGCAATCCAAACATGGACTAT
AAAAATGGTGAACATCATTCACCTTCTCACA
TAATCCATAACTACAGTGCAGCTCCGGGCATGTTCAACA
GCTCTCTTCATGCCCTGCATCTCCAAAACAA
GGAGAATGACATGCTTTCCCACACAGCTAATGGGTTATC
AAAGATGCTTCCAGCTCTTAACCATGATAGA
ACTGCTTGTGTCCAAGGAGGCTTACACAAATTAAGTGAT
GCTAATGGTCAGGAAAAGCAGCCATTGGCAC
TAGTCCAGGGTGTGGCTTCTGGTGCAGAGGACAACGATG
AGGTCTGGTCAGACAGCGAGCAGAGCTTTCT
GGATCCTGACATTGGGGGAGTGGCCGTGGCTCCAACTCA
TGGGTCAATTCTCATTGAGTGTGCAAAGCGT
GAGCTGCATGCCACAACCCCTTTAAAGAATCCCAATAGG
AATCACCCCACCAGGATCTCCCTCGTCTTTT
ACCAGCATAAGAGCATGAATGAGCCAAAACATGGCTTG
GCTCTTTGGGAAGCCAAAATGGCTGAAAAAGC
CCGTGAGAAAGAGGAAGAGTGTGAAAAGTATGGCCCAG
ACTATGTGCCTCAGAAATCCCATGGCAAAAAA
GTGAAACGGGAGCCTGCTGAGCCACATGAAACTTCAGA
GCCCACTTACCTGCGTTTCATCAAGTCTCTTG
CCGAAAGGACCATGTCCGTGACCACAGACTCCACAGTAA
CTACATCTCCATATGCCTTCACTCGGGTCAC
AGGGCCTTACAACAGATATATATGATATCACCCCCTTTT
GTTGGTTACCTCACTTGAAAAGACCACAACC
AACCTGTCAGTAGTATAGTTCTCATGACGTGGGCAGTGG
GGAAAGGTCACAGTATTCATGACAAATGTGG
TGGGAAAAACCTCAGCTCACCAGCAACAAAAGAGGTTA
TCTTACCATAGCACTTAATTTTCACTGGCTCC
CAAGTGGTCACAGATGGCATCTAGGAAAAGACCAAAGC
ATTCTATGCAAAAAGAAGGTGGGGAAGAAAGT
GTTCCGCAATTTACATTTTTAAACACTGGTTCTATTATTG
GACGAGATGATATGTAAATGTGATCCCCCC
CCCCCGCTTACAACTCTACACATCTGTGACCACTTTTAAT
AATATCAAGTTTGCATAGTCATGGAACACA
AATCAAACAAGTACTGTAGTATTACAGTGACAGGAATCT
TAAAATACCATCTGGTGCTGAATATATGATG
TACTGAAATACTGGAATTATGGCTTTTTGAAATGCAGTTT
TTACTGTAATCTTAACTTTTATTTATCAAA
ATAGCTACAGGAAACATGAATAGCAGGAAAACACTGAA
TTTGTTTGGATGTTCTAAGAAATGGTGCTAAG
AAAATGGTGTCTTTAATAGCTAAAAATTTAATGCCTTTAT
ATCATCAAGATGCTATCAGTGTACTCCAGT
GCCCTTGAATAATAGGGGTACCTTTTCATTCAAGTTTTTA
TCATAATTACCTATTCTTACACAAGCTTAG
TTTTTAAAATGTGGACATTTTAAAGGCCTCTGGATTTTGC
TCATCCAGTGAAGTCCTTGTAGGACAATAA
ACGTATATATGTACATATATACACAAACATGTATATGTG
CACACACATGTATATGTATAAATATTTTAAA
TGGTGTTTTAGAAGCACTTTGTCTACCTAAGCTTTGACAA
CTTGAACAATGCTAAGGTACTGAGATGTTT
AAAAAACAAGTTTACTTTCATTTTAGAATGCAAAGTTGA
TTTTTTTAAGGAAACAAAGAAAGCTTTTAAA
ATATTTTTGCTTTTAGCCATGCATCTGCTGATGAGCAATT
GTGTCCATTTTTAACACAGCCAGTTAAATC
CACCATGGGGCTTACTGGATTCAAGGGAATACGTTAGTC
CACAAAACATGTTTTCTGGTGCTCATCTCAC
ATGCTATACTGTAAAACAGTTTTATACAAAATTGTATGA
CAAGTTCATTGCTCAAAAATGTACAGTTTTA
AGAATTTTCTATTAACTGCAGGTAATAATTAGCTGCATG
CTGCAGACTCAACAAAGCTAGTTCACTGAAG
CCTATGCTATTTTATGGATCATAGGCTCTTCAGAGAACTG
AATGGCAGTCTGCCTTTGTGTTGATAATTA
TGTACATTGTGACGTTGTCATTTCTTAGCTTAAGTGTCCT
CTTTAACAAGAGGATTGAGCAGACTGATGC
CTGCATAAGATGAATAAACAGGGTTAGTTCCATGTGAAT
CTGTCAGTTAAAAAGAAACAAAAACAGGCAG
CTGGTTTGCTGTGGTGGTTTTAAATCATTAATTTGTATAA
AGAAGTGAAAGAGTTGTATAGTAAATTAAA
TTGTAAACAAAACTTTTTTAATGCAATGCTTTAGTATTTT
AGTACTGTAAAAAAATTAAATATATACATA
TATATATATATATATATATATATATATATGAGTTTGAAGC
AGAATTCACATCATGATGGTGCTACTCAGC
CTGCTACAAATATATCATAATGTGAGCTAAGAATTCATT
AAATGTTTGAGTGATGTTCCTACTTGTCATA
TACCTCAACACTAGTTTGGCAATAGGATATTGAACTGAG
AGTGAAAGCATTGTGTACCATCATTTTTTTC
CAAGTCCTTTTTTTTATTGTTAAAAAAAAAAGCATACCTT
TTTTCAATACTTGATTTCTTAGCAAGTATA
ACTTGAACTTCAACCTTTTTGTTCTAAAAATTCAGGGATA
TTTCAGCTCATGCTCTCCCTATGCCAACAT
GTCACCTGTGTTTATGTAAAATTGTTGTAGGTTAATAAAT
ATATTCTTTGTCAGGGATTTAACCCTTTTA
TTTTGAATCCCTTCTATTTTACTTGTACATGTGCTGATGT
AACTAAAACTAATTTTGTAAATCTGTTGGC
TCTTTTTATTGTAAAGAAAAGCATTTTAAAAGTTTGAGG
AATCTTTTGACTGTTTCAAGCAGGAAAAAAA
AATTACATGAAAATAGAATGCACTGAGTTGATAAAGGG
AAAAATTGTAAGGCAGGAGTTTGGCAAGTGGC
TGTTGGCCAGAGACTTACTTGTAACTCTCTAAATGAAGTT
TTTTTGATCCTGTAATCACTGAAGGTACAT
ACTCCATGTGGACTTCCCTTAAACAGGCAAACACCTACA
GGTATGGTGTGCAACAGATTGTACAATTACA
TTTTGGCCTAAATACATTTTTGCTTACTAGTATTTAAAAT
AAATTCTTAATCAGAGGAGGCCTTTGGGTT
TTATTGGTCAAATCTTTGTAAGCTGGCTTTTGTCTTTTTA
AAAAATTTCTTGAATTTGTGGTTGTGTCCA
ATTTGCAAACATTTCCAAAAATGTTTGCTTTGCTTACAAA
CCACATGATTTTAATGTTTTTTGTATACCA
TAATATCTAGCCCCAAACATTTGATTACTACATGTGCATT
GGTGATTTTGATCATCCATTCTTAATATTT
GATTTCTGTGTCACCTACTGTCATTTGTTAAACTGCTGGC
CAACAAGAACAGGAAGTATAGTTTGGGGGG
TTGGGGAGAGTTTACATAAGGAAGAGAAGAAATTGAGT
GGCATATTGTAAATATCAGATCTATAATTGTA
AATATAAAACCTGCCTCAGTTAGAATGAATGGAAAGCAG
ATCTACAATTTGCTAATATAGGAATATCAGG
TTGACTATATAGCCATACTTGAAAATGCTTCTGAGTGGT
GTCAACTTTACTTGAATGAATTTTTCATCTT
GATTGACGCACAGTGATGTACAGTTCACTTCTGAAGCTA
GTGGTTAACTTGTGTAGGAAACTTTTGCAGT
TTGACACTAAGATAACTTCTGTGTGCATTTTTCTATGCTT
TTTTAAAAACTAGTTTCATTTCATTTTCAT
GAGATGTTTGGTTTATAAGATCTGAGGATGGTTATAAAT
ACTGTAAGTATTGTAATGTTATGAATGCAGG
TTATTTGAAAGCTGTTTATTATTATATCATTCCTGATAAT
GCTATGTGAGTGTTTTTAATAAAATTTATA
TTTATTTAATGCACTCTAA
PREDICTED:XM_011532043.1GTAGAGAAGCAGAAGGAAGCAAGATGGCTGCCCTTTAG
Homo sapiens
GATTTGTTAGAAAGGAGACCCGACTGCAACTG
tetCTGGATTGCTGCAAGGCTGAGGGACGAGAACGAGGCTG
methylcytosineGCAAACATTCAGCAGCACACCCTCTCAAGATT
dioxygenase 2GTTTACTTGCCTTTGCTCCTGTTGAGTTACAACGCTTGGA
(TET2),AGCAGGAGATGGGCTCAGCAGCAGCCAATA
transcriptGGACATGATCCAGGAAGAGCAGTAAGGGACTGAGCTGC
variant X7,TGAATTCAACTAGAGGGCAGCCTTGTGGATGG
mRNACCCCGAAGCAAGCCTGATGGAACAGGATAGAACCAACC
[SEQ ID NO:ATGTTGAGGGCAACAGACTAAGTCCATTCCTG
956]ATACCATCACCTCCCATTTGCCAGACAGAACCTCTGGCT
ACAAAGCTCCAGAATGGAAGCCCACTGCCTG
AGAGAGCTCATCCAGAAGTAAATGGAGACACCAAGTGG
CACTCTTTCAAAAGTTATTATGGAATACCCTG
TATGAAGGGAAGCCAGAATAGTCGTGTGAGTCCTGACTT
TACACAAGAAAGTAGAGGGTATTCCAAGTGT
TTGCAAAATGGAGGAATAAAACGCACAGTTAGTGAACCT
TCTCTCTCTGGGCTCCTTCAGATCAAGAAAT
TGAAACAAGACCAAAAGGCTAATGGAGAAAGACGTAAC
TTCGGGGTAAGCCAAGAAAGAAATCCAGGTGA
AAGCAGTCAACCAAATGTCTCCGATTTGAGTGATAAGAA
AGAATCTGTGAGTTCTGTAGCCCAAGAAAAT
GCAGTTAAAGATTTCACCAGTTTTTCAACACATAACTGC
AGTGGGCCTGAAAATCCAGAGCTTCAGATTC
TGAATGAGCAGGAGGGGAAAAGTGCTAATTACCATGAC
AAGAACATTGTATTACTTAAAAACAAGGCAGT
GCTAATGCCTAATGGTGCTACAGTTTCTGCCTCTTCCGTG
GAACACACACATGGTGAACTCCTGGAAAAA
ACACTGTCTCAATATTATCCAGATTGTGTTTCCATTGCGG
TGCAGAAAACCACATCTCACATAAATGCCA
TTAACAGTCAGGCTACTAATGAGTTGTCCTGTGAGATCA
CTCACCCATCGCATACCTCAGGGCAGATCAA
TTCCGCACAGACCTCTAACTCTGAGCTGCCTCCAAAGCC
AGCTGCAGTGGTGAGTGAGGCCTGTGATGCT
GATGATGCTGATAATGCCAGTAAACTAGCTGCAATGCTA
AATACCTGTTCCTTTCAGAAACCAGAACAAC
TACAACAACAAAAATCAGTTTTTGAGATATGCCCATCTC
CTGCAGAAAATAACATCCAGGGAACCACAAA
GCTAGCGTCTGGTGAAGAATTCTGTTCAGGTTCCAGCAG
CAATTTGCAAGCTCCTGGTGGCAGCTCTGAA
CGGTATTTAAAACAAAATGAAATGAATGGTGCTTACTTC
AAGCAAAGCTCAGTGTTCACTAAGGATTCCT
TTTCTGCCACTACCACACCACCACCACCATCACAATTGCT
TCTTTCTCCCCCTCCTCCTCTTCCACAGGT
TCCTCAGCTTCCTTCAGAAGGAAAAAGCACTCTGAATGG
TGGAGTTTTAGAAGAACACCACCACTACCCC
AACCAAAGTAACACAACACTTTTAAGGGAAGTGAAAAT
AGAGGGTAAACCTGAGGCACCACCTTCCCAGA
GTCCTAATCCATCTACACATGTATGCAGCCCTTCTCCGAT
GCTTTCTGAAAGGCCTCAGAATAATTGTGT
GAACAGGAATGACATACAGACTGCAGGGACAATGACTG
TTCCATTGTGTTCTGAGAAAACAAGACCAATG
TCAGAACACCTCAAGCATAACCCACCAATTTTTGGTAGC
AGTGGAGAGCTACAGGACAACTGCCAGCAGT
TGATGAGAAACAAAGAGCAAGAGATTCTGAAGGGTCGA
GACAAGGAGCAAACACGAGATCTTGTGCCCCC
AACACAGCACTATCTGAAACCAGGATGGATTGAATTGAA
GGCCCCTCGTTTTCACCAAGCGGAATCCCAT
CTAAAACGTAATGAGGCATCACTGCCATCAATTCTTCAG
TATCAACCCAATCTCTCCAATCAAATGACCT
CCAAACAATACACTGGAAATTCCAACATGCCTGGGGGGC
TCCCAAGGCAAGCTTACACCCAGAAAACAAC
ACAGCTGGAGCACAAGTCACAAATGTACCAAGTTGAAAT
GAATCAAGGGCAGTCCCAAGGTACAGTGGAC
CAACATCTCCAGTTCCAAAAACCCTCACACCAGGTGCAC
TTCTCCAAAACAGACCATTTACCAAAAGCTC
ATGTGCAGTCACTGTGTGGCACTAGATTTCATTTTCAACA
AAGAGCAGATTCCCAAACTGAAAAACTTAT
GTCCCCAGTGTTGAAACAGCACTTGAATCAACAGGCTTC
AGAGACTGAGCCATTTTCAAACTCACACCTT
TTGCAACATAAGCCTCATAAACAGGCAGCACAAACACA
ACCATCCCAGAGTTCACATCTCCCTCAAAACC
AGCAACAGCAGCAAAAATTACAAATAAAGAATAAAGAG
GAAATACTCCAGACTTTTCCTCACCCCCAAAG
CAACAATGATCAGCAAAGAGAAGGATCATTCTTTGGCCA
GACTAAAGTGGAAGAATGTTTTCATGGTGAA
AATCAGTATTCAAAATCAAGCGAGTTCGAGACTCATAAT
GTCCAAATGGGACTGGAGGAAGTACAGAATA
TAAATCGTAGAAATTCCCCTTATAGTCAGACCATGAAAT
CAAGTGCATGCAAAATACAGGTTTCTTGTTC
AAACAATACACACCTAGTTTCAGAGAATAAAGAACAGA
CTACACATCCTGAACTTTTTGCAGGAAACAAG
ACCCAAAACTTGCATCACATGCAATATTTTCCAAATAAT
GTGATCCCAAAGCAAGATCTTCTTCACAGGT
GCTTTCAAGAACAGGAGCAGAAGTCACAACAAGCTTCA
GTTCTACAGGGATATAAAAATAGAAACCAAGA
TATGTCTGGTCAACAAGCTGCGCAACTTGCTCAGCAAAG
GTACTTGATACATAACCATGCAAATGTTTTT
CCTGTGCCTGACCAGGGAGGAAGTCACACTCAGACCCCT
CCCCAGAAGGACACTCAAAAGCATGCTGCTC
TAAGGTGGCATCTCTTACAGAAGCAAGAACAGCAGCAA
ACACAGCAACCCCAAACTGAGTCTTGCCATAG
TCAGATGCACAGGCCAATTAAGGTGGAACCTGGATGCAA
GCCACATGCCTGTATGCACACAGCACCACCA
GAAAACAAAACATGGAAAAAGGTAACTAAGCAAGAGAA
TCCACCTGCAAGCTGTGATAATGTGCAGCAAA
AGAGCATCATTGAGACCATGGAGCAGCATCTGAAGCAGT
TTCACGCCAAGTCGTTATTTGACCATAAGGC
TCTTACTCTCAAATCACAGAAGCAAGTAAAAGTTGAAAT
GTCAGGGCCAGTCACAGTTTTGACTAGACAA
ACCACTGCTGCAGAACTTGATAGCCACACCCCAGCTTTA
GAGCAGCAAACAACTTCTTCAGAAAAGACAC
CAACCAAAAGAACAGCTGCTTCTGTTCTCAATAATTTTAT
AGAGTCACCTTCCAAATTACTAGATACTCC
TATAAAAAATTTATTGGATACACCTGTCAAGACTCAATA
TGATTTCCCATCTTGCAGATGTGTAGAGCAA
ATTATTGAAAAAGATGAAGGTCCTTTTTATACCCATCTA
GGAGCAGGTCCTAATGTGGCAGCTATTAGAG
AAATCATGGAAGAAAGGTATACAAGTACTTGCCTTTACT
CCTGCATGTAGAAGACTCTTATGAGCGAGAT
AATGCAGAGAAGGCCTTTCATATAAATTTATACAGCTCT
GAGCTGTTCTTCTTCTAGGGTGCCTTTTCAT
TAAGAGGTAGGCAGTATTATTATTAAAGTACTTAGGATA
CATTGGGGCAGCTAGGACATATTCAGTATCA
TTCTTGCTCCATTTCCAAATTATTCATTTCTAAATTAGCA
TGTAGAAGTTCACTAAATAATCATCTAGTG
GCCTGGCAGAAATAGTGAATTTCCCTAAGTGCCTTTTTTT
TGTTGTTTTTTTGTTTTGTTTTTTAAACAA
GCAGTAGGTGGTGCTTTGGTCATAAGGGAAGATATAGTC
TATTTCTAGGACTATTCCATATTTTCCATGT
GGCTGGATACTAACTATTTGCCAGCCTCCTTTTCTAAATT
GTGAGACATTCTTGGAGGAACAGTTCTAAC
TAAAATCTATTATGACTCCCCAAGTTTTAAAATAGCTAA
ATTTAGTAAGGGAAAAAATAGTTTATGTTTT
AGAAGACTGAACTTAGCAAACTAACCTGAATTTTGTGCT
TTGTGAAATTTTATATCGAAATGAGCTTTCC
CATTTTCACCCACATGTAATTTACAAAATAGTTCATTACA
ATTATCTGTACATTTTGATATTGAGGAAAA
ACAAGGCTTAAAAACCATTATCCAGTTTGCTTGGCGTAG
ACCTGTTTAAAAAATAATAAACCGTTCATTT
CTCAGGATGTGGTCATAGAATAAAGTTATGCTCAAATGT
TCAAA
TABLE 1 — gRNA Targeting Domains for TET2 introns and intron-exon junctions. In the “Id” field, the first number relates to the target gene, here, indicating human TET2; the second number indicates the intron number (for example, a “1” indicates the gRNA targets a target sequence in the intron between exon 1 and exon 2); the final number is a unique identifier for the gRNA. SEQ
genomic location (hg38) ofgRNA targeting domainID
Idstrandtarget sequencesequenceNO:
54790_1_6+chr4: 105147018-105147038UUCUCCCCUUCGCUUUUUCU1000
54790_1_8+chr4: 105147019-105147039UCUCCCCUUCGCUUUUUCUC1001
54790_1_12+chr4: 105147027-105147047UCGCUUUUUCUCGGGCUUCC1002
54790_1_13+chr4: 105147028-105147048CGCUUUUUCUCGGGCUUCCA1003
54790_1_16+chr4: 105147033-105147053UUUCUCGGGCUUCCAGGGAC1004
54790_1_18+chr4: 105147034-105147054UUCUCGGGCUUCCAGGGACU1005
54790_1_22+chr4: 105147035-105147055UCUCGGGCUUCCAGGGACUG1006
54790_1_30+chr4: 105147072-105147092UGUCACCCACAAAUACCAAG1007
54790_1_32+chr4: 105147073-105147093GUCACCCACAAAUACCAAGA1008
54790_1_36+chr4: 105147079-105147099CACAAAUACCAAGAGGGAAG1009
54790_1_38+chr4: 105147080-105147100ACAAAUACCAAGAGGGAAGA1010
54790_1_40+chr4: 105147099-105147119AGGGAAGCUUCACAAAUUAC1011
54790_1_43+chr4: 105147115-105147135UUACUGGAGCCUCUUCAACA1012
54790_1_59+chr4: 105147240-105147260CCUUUGUGCCUCCGACGAGC1013
54790_1_63+chr4: 105147248-105147268CCUCCGACGAGCCGGUUUCC1014
54790_1_83+chr4: 105147314-105147334UUUCUAAAAUAGUUCAGCUU1015
54790_1_84+chr4: 105147315-105147335UUCUAAAAUAGUUCAGCUUU1016
54790_1_86+chr4: 105147316-105147336UCUAAAAUAGUUCAGCUUUG1017
54790_1_88+chr4: 105147317-105147337CUAAAAUAGUUCAGCUUUGG1018
54790_1_112+chr4: 105147415-105147435ACCUCAGAGAGAACACUGAU1019
54790_1_113+chr4: 105147416-105147436CCUCAGAGAGAACACUGAUA1020
54790_1_116+chr4: 105147445-105147465UCGACCCUUUUAUCAGCUGU1021
54790_1_119+chr4: 105147446-105147466CGACCCUUUUAUCAGCUGUA1022
54790_1_122+chr4: 105147451-105147471CUUUUAUCAGCUGUAGGGUC1023
54790_1_123+chr4: 105147452-105147472UUUUAUCAGCUGUAGGGUCU1024
54790_1_127+chr4: 105147457-105147477UCAGCUGUAGGGUCUGGGUC1025
54790_1_129+chr4: 105147458-105147478CAGCUGUAGGGUCUGGGUCU1026
54790_1_134+chr4: 105147498-105147518CUACCUUCUUAUCCCCCUUU1027
54790_1_136+chr4: 105147499-105147519UACCUUCUUAUCCCCCUUUA1028
54790_1_137+chr4: 105147500-105147520ACCUUCUUAUCCCCCUUUAG1029
54790_1_138+chr4: 105147501-105147521CCUUCUUAUCCCCCUUUAGG1030
54790_1_147+chr4: 105147524-105147544CUGUACGAAGUGAAUGUCAC1031
54790_1_149+chr4: 105147525-105147545UGUACGAAGUGAAUGUCACA1032
54790_1_152+chr4: 105147530-105147550GAAGUGAAUGUCACAGGGAG1033
54790_1_155+chr4: 105147536-105147556AAUGUCACAGGGAGUGGAAU1034
54790_1_158+chr4: 105147550-105147570UGGAAUUGGAGUACACUGAG1035
54790_1_159+chr4: 105147551-105147571GGAAUUGGAGUACACUGAGU1036
54790_1_170+chr4: 105147588-105147608AAGUCCGCGCGUUUUGUUAG1037
54790_1_179+chr4: 105147604-105147624UUAGCGGCGCUGAGUGAAAG1038
54790_1_184+chr4: 105147622-105147642AGAGGAAAGAAUAGUUUCUC1039
54790_1_189+chr4: 105147658-105147678ACCAGAACUCACUUUUCUCA1040
54790_1_194+chr4: 105147676-105147696CAAGGUACAUAAGUCAGCGC1041
54790_1_195+chr4: 105147677-105147697AAGGUACAUAAGUCAGCGCU1042
54790_1_198+chr4: 105147695-105147715CUGGGCUGAGCCUUCCAGCC1043
54790_1_201+chr4: 105147696-105147716UGGGCUGAGCCUUCCAGCCU1044
54790_1_203+chr4: 105147697-105147717GGGCUGAGCCUUCCAGCCUG1045
54790_1_209+chr4: 105147720-105147740AAUGUAUGUAAGAGAAUUUA1046
54790_1_210+chr4: 105147737-105147757UUAUGGACAAAUCUGUGUCC1047
54790_1_216+chr4: 105147769-105147789UCUCCCGAAUCAGCUUCGUU1048
54790_1_218+chr4: 105147777-105147797AUCAGCUUCGUUUGGUUCCU1049
54790_1_220+chr4: 105147788-105147808UUGGUUCCUUGGUAAGUGAC1050
54790_1_225+chr4: 105147800-105147820UAAGUGACAGGCAGACACAA1051
54790_1_226+chr4: 105147804-105147824UGACAGGCAGACACAAAGGC1052
54790_1_227+chr4: 105147810-105147830GCAGACACAAAGGCAGGCGC1053
54790_1_229+chr4: 105147815-105147835CACAAAGGCAGGCGCAGGCC1054
54790_1_231+chr4: 105147816-105147836ACAAAGGCAGGCGCAGGCCC1055
54790_1_233+chr4: 105147817-105147837CAAAGGCAGGCGCAGGCCCG1056
54790_1_236+chr4: 105147820-105147840AGGCAGGCGCAGGCCCGGGG1057
54790_1_239+chr4: 105147821-105147841GGCAGGCGCAGGCCCGGGGA1058
54790_1_240+chr4: 105147822-105147842GCAGGCGCAGGCCCGGGGAG1059
54790_1_241+chr4: 105147823-105147843CAGGCGCAGGCCCGGGGAGG1060
54790_1_243+chr4: 105147826-105147846GCGCAGGCCCGGGGAGGGGG1061
54790_1_246+chr4: 105147827-105147847CGCAGGCCCGGGGAGGGGGC1062
54790_1_248+chr4: 105147830-105147850AGGCCCGGGGAGGGGGCGGG1063
54790_1_251+chr4: 105147831-105147851GGCCCGGGGAGGGGGCGGGA1064
54790_1_252+chr4: 105147832-105147852GCCCGGGGAGGGGGCGGGAG1065
54790_1_253+chr4: 105147833-105147853CCCGGGGAGGGGGCGGGAGG1066
54790_1_256+chr4: 105147836-105147856GGGGAGGGGGCGGGAGGGGG1067
54790_1_257+chr4: 105147837-105147857GGGAGGGGGCGGGAGGGGGU1068
54790_1_260+chr4: 105147838-105147858GGAGGGGGCGGGAGGGGGUG1069
54790_1_263+chr4: 105147851-105147871GGGGGUGGGGAGCGCAGCGU1070
54790_1_264+chr4: 105147869-105147889GUUGGAGUUGCAAGACUGCA1071
54790_1_268+chr4: 105147874-105147894AGUUGCAAGACUGCAAGGUC1072
54790_1_269+chr4: 105147875-105147895GUUGCAAGACUGCAAGGUCA1073
54790_1_270+chr4: 105147876-105147896UUGCAAGACUGCAAGGUCAG1074
54790_1_280+chr4: 105147955-105147975GUCCCAUCCAAAUUUCUCUU1075
54790_1_281+chr4: 105147968-105147988UUCUCUUUGGCUUCUCUCUU1076
54790_1_298+chr4: 105148092-105148112AUCUUGCUGAAUCUUUUCAC1077
54790_1_300+chr4: 105148093-105148113UCUUGCUGAAUCUUUUCACU1078
54790_1_306+chr4: 105148124-105148144UCUAGUUUUAUUAAGCUAAU1079
54790_1_308+chr4: 105148125-105148145CUAGUUUUAUUAAGCUAAUA1080
54790_1_313+chr4: 105148134-105148154UUAAGCUAAUAGGGUUUGUA1081
54790_1_323+chr4: 105148167-105148187ACCUAUGACAUAAUGAAGUG1082
54790_1_325+chr4: 105148172-105148192UGACAUAAUGAAGUGUGGCC1083
54790_1_328+chr4: 105148184-105148204GUGUGGCCUGGAUAGACUCC1084
54790_1_329+chr4: 105148189-105148209GCCUGGAUAGACUCCUGGAA1085
54790_1_332+chr4: 105148220-105148240GAAAUAUAAGUGUUAUUUGC1086
54790_1_340+chr4: 105148257-105148277AUAUACUUUUAAUUACAUUG1087
54790_1_343+chr4: 105148258-105148278UAUACUUUUAAUUACAUUGA1088
54790_1_357+chr4: 105148300-105148320AAUGUUUAAGAAUUGAGAAA1089
54790_1_360+chr4: 105148315-105148335AGAAAAGGCUUAUUUUCCAG1090
54790_1_373+chr4: 105148368-105148388AUUUAUAUAUUUACGUGUCU1091
54790_1_375+chr4: 105148369-105148389UUUAUAUAUUUACGUGUCUA1092
54790_1_380+chr4: 105148374-105148394AUAUUUACGUGUCUAGGGAG1093
54790_1_388+chr4: 105148434-105148454GUGCUUUUUCCCCUUCAGUC1094
54790_1_390+chr4: 105148435-105148455UGCUUUUUCCCCUUCAGUCA1095
54790_1_398+chr4: 105148445-105148465CCUUCAGUCAGGGAUUAUAA1096
54790_1_399+chr4: 105148446-105148466CUUCAGUCAGGGAUUAUAAU1097
54790_1_406+chr4: 105148491-105148511AUCAACAAAUGAUCCAUCAU1098
54790_1_410+chr4: 105148511-105148531AGGAAUAAGAUUGUAUCUUA1099
54790_1_411+chr4: 105148512-105148532GGAAUAAGAUUGUAUCUUAA1100
54790_1_415+chr4: 105148519-105148539GAUUGUAUCUUAAGGGAAGU1101
54790_1_416+chr4: 105148520-105148540AUUGUAUCUUAAGGGAAGUU1102
54790_1_423+chr4: 105148542-105148562GAUUCACAGAGAAAAGACAU1103
54790_1_424+chr4: 105148547-105148567ACAGAGAAAAGACAUUGGUU1104
54790_1_426+chr4: 105148552-105148572GAAAAGACAUUGGUUUGGUU1105
54790_1_429+chr4: 105148565-105148585UUUGGUUUGGUGUGAUACUG1106
54790_1_430+chr4: 105148566-105148586UUGGUUUGGUGUGAUACUGU1107
54790_1_435+chr4: 105148579-105148599AUACUGUGGGUAUUGUUGCC1108
54790_1_441+chr4: 105148611-105148631UCAUUACAUUUGCAUUUUAA1109
54790_1_450+chr4: 105148629-105148649AAUGGAAAGUUGAAAUACUA1110
54790_1_451+chr4: 105148630-105148650AUGGAAAGUUGAAAUACUAA1111
54790_1_455+chr4: 105148631-105148651UGGAAAGUUGAAAUACUAAG1112
54790_1_464+chr4: 105148677-105148697UAUGUGUGCUUAAUAAUGUU1113
54790_1_482+chr4: 105148741-105148761AAAUGUUAAUAAGCAGAGAA1114
54790_1_487+chr4: 105148756-105148776GAGAACGGUUAAUGAAGUGU1115
54790_1_493+chr4: 105148791-105148811AAGUUUAGAAGACAAUUUAU1116
54790_1_497+chr4: 105148803-105148823CAAUUUAUAGGAUUAAAAAA1117
54790_1_503+chr4: 105148811-105148831AGGAUUAAAAAAUGGAUAGA1118
54790_1_526+chr4: 105148942-105148962UUGCUUUAAUCAUUGAUACG1119
54790_1_528+chr4: 105148943-105148963UGCUUUAAUCAUUGAUACGU1120
54790_1_529+chr4: 105148944-105148964GCUUUAAUCAUUGAUACGUG1121
54790_1_537+chr4: 105148965-105148985GGUUCUUUCACAUGAUUACA1122
54790_1_539+chr4: 105148966-105148986GUUCUUUCACAUGAUUACAA1123
54790_1_547+chr4: 105148989-105149009AGAAGCAUUACUCAUCUCUG1124
54790_1_551+chr4: 105149000-105149020UCAUCUCUGUGGAAUAGAAA1125
54790_1_552+chr4: 105149008-105149028GUGGAAUAGAAACGGUUCAU1126
54790_1_561+chr4: 105149047-105149067CUAAAAUUAAAACAAAAAUU1127
54790_1_564+chr4: 105149072-105149092UUUACCAUUAAUGCUGUUCA1128
54790_1_573+chr4: 105149094-105149114GUAAACUAUCGAGAAAACUA1129
54790_1_587+chr4: 105149162-105149182ACAAACUAAUAUUUACUUUU1130
54790_1_589+chr4: 105149163-105149183CAAACUAAUAUUUACUUUUU1131
54790_1_590+chr4: 105149164-105149184AAACUAAUAUUUACUUUUUG1132
54790_1_597+chr4: 105149185-105149205GGACAACUUUUCAAAUGUUG1133
54790_1_601+chr4: 105149202-105149222UUGUGGUAUAUACUGUCUUC1134
54790_1_609+chr4: 105149262-105149282AUAAAUAAGAAUAACUACAU1135
54790_1_614+chr4: 105149290-105149310AAUUUUGAAUACAACUAUGA1136
54790_1_638+chr4: 105149401-105149421AAAGUAUUUCAGUGAUUAUA1137
54790_1_645+chr4: 105149438-105149458UUAGUCACUUUAUCCUUUGU1138
54790_1_658+chr4: 105149466-105149486AGAAAUUAUUUUAAUAAGUA1139
54790_1_659+chr4: 105149467-105149487GAAAUUAUUUUAAUAAGUAU1140
54790_1_660+chr4: 105149468-105149488AAAUUAUUUUAAUAAGUAUG1141
54790_1_672+chr4: 105149533-105149553UAUAUGUGAUCAUACUACCU1142
54790_1_674+chr4: 105149553-105149573AGGUGCUCCAAAAAUUCCAU1143
54790_1_676+chr4: 105149563-105149583AAAAUUCCAUAGGACUGUCU1144
54790_1_677+chr4: 105149564-105149584AAAUUCCAUAGGACUGUCUU1145
54790_1_682+chr4: 105149579-105149599GUCUUGGGUUAUUGAAUUUU1146
54790_1_686+chr4: 105149592-105149612GAAUUUUAGGAACAUGAUAA1147
54790_1_721+chr4: 105149739-105149759UAUUUGCCAAACUCUUCUUA1148
54790_1_724+chr4: 105149750-105149770CUCUUCUUAAGGCUUUAAUU1149
54790_1_732+chr4: 105149780-105149800UGCCAGUUUAUGCCAGAAGC1150
54790_1_735+chr4: 105149783-105149803CAGUUUAUGCCAGAAGCCGG1151
54790_1_740+chr4: 105149802-105149822GAGGAAUUGAUAUGAUUUUG1152
54790_1_741+chr4: 105149808-105149828UUGAUAUGAUUUUGAGGCAG1153
54790_1_743+chr4: 105149815-105149835GAUUUUGAGGCAGUGGCACA1154
54790_1_747+chr4: 105149831-105149851CACAUGGUCCUACUAGACAU1155
54790_1_755+chr4: 105149876-105149896CAAGUGAAGUGCACCUGCCA1156
54790_1_762+chr4: 105149910-105149930AAGAAUUCCAAAGUCCUUAU1157
54790_1_763+chr4: 105149911-105149931AGAAUUCCAAAGUCCUUAUU1158
54790_1_764+chr4: 105149917-105149937CCAAAGUCCUUAUUGGGCAC1159
54790_1_767+chr4: 105149929-105149949UUGGGCACUGGUCUUGUAUU1160
54790_1_771+chr4: 105149942-105149962UUGUAUUAGGUAACAACAAC1161
54790_1_796+chr4: 105150097-105150117AAGCCCUUCUUAUGAUUCAU1162
54790_1_806+chr4: 105150146-105150166AUCCUGCCCAAAGUCUGAGU1163
54790_1_817+chr4: 105150205-105150225UAAAAUAUCUUCAAAAGUUA1164
54790_1_856+chr4: 105150368-105150388AUCUAGCAAUUUCAAAUCGC1165
54790_1_867+chr4: 105150434-105150454AAUGUUAUUGUUUCCUACCU1166
54790_1_872+chr4: 105150435-105150455AUGUUAUUGUUUCCUACCUU1167
54790_1_874+chr4: 105150441-105150461UUGUUUCCUACCUUGGGAAC1168
54790_1_879+chr4: 105150453-105150473UUGGGAACAGGCUAAAACUU1169
54790_1_893+chr4: 105150529-105150549CCAUUGCACAGUAGUUCUUA1170
54790_1_895+chr4: 105150539-105150559GUAGUUCUUAAGGAUAGUAA1171
54790_1_902+chr4: 105150589-105150609UCCCAAGCCAACUUUACAAU1172
54790_1_904+chr4: 105150603-105150623UACAAUUGGAGCCUUCACUG1173
54790_1_907+chr4: 105150604-105150624ACAAUUGGAGCCUUCACUGU1174
54790_1_913+chr4: 105150630-105150650GACCAGUUGCCAAGUAGAGC1175
54790_1_914+chr4: 105150633-105150653CAGUUGCCAAGUAGAGCUGG1176
54790_1_917+chr4: 105150641-105150661AAGUAGAGCUGGUGGUUAUC1177
54790_1_919+chr4: 105150642-105150662AGUAGAGCUGGUGGUUAUCU1178
54790_1_926+chr4: 105150701-105150721CCAAAUAUACAGUAUUUACU1179
54790_1_939+chr4: 105150768-105150788GAAUACUGUGACAUUAUUGA1180
54790_1_941+chr4: 105150771-105150791UACUGUGACAUUAUUGAAGG1181
54790_1_944+chr4: 105150791-105150811AGGUUAUGCAGUACAUCUGU1182
54790_1_945+chr4: 105150796-105150816AUGCAGUACAUCUGUUGGUU1183
54790_1_948+chr4: 105150807-105150827CUGUUGGUUUGGUAUAUAGU1184
54790_1_954+chr4: 105150815-105150835UUGGUAUAUAGUAGGAGAGA1185
54790_1_955+chr4: 105150816-105150836UGGUAUAUAGUAGGAGAGAA1186
54790_1_960+chr4: 105150823-105150843UAGUAGGAGAGAAGGGUUCC1187
54790_1_963+chr4: 105150826-105150846UAGGAGAGAAGGGUUCCAGG1188
54790_1_964+chr4: 105150827-105150847AGGAGAGAAGGGUUCCAGGA1189
54790_1_968+chr4: 105150832-105150852AGAAGGGUUCCAGGAGGGAA1190
54790_1_969+chr4: 105150833-105150853GAAGGGUUCCAGGAGGGAAA1191
54790_1_971+chr4: 105150834-105150854AAGGGUUCCAGGAGGGAAAG1192
54790_1_994+chr4: 105150989-105151009UUCUCAAAAGAAUAGAUAUU1193
54790_1_1002+chr4: 105151016-105151036CCAUUCCAAAUAACAAAUUU1194
54790_1_1004+chr4: 105151020-105151040UCCAAAUAACAAAUUUUGGA1195
54790_1_1005+chr4: 105151021-105151041CCAAAUAACAAAUUUUGGAU1196
54790_1_1007+chr4: 105151026-105151046UAACAAAUUUUGGAUGGGCG1197
54790_1_1013+chr4: 105151056-105151076UGCCUGUAAUCCUAGCACUU1198
54790_1_1014+chr4: 105151057-105151077GCCUGUAAUCCUAGCACUUU1199
54790_1_1016+chr4: 105151060-105151080UGUAAUCCUAGCACUUUGGG1200
54790_1_1017+chr4: 105151066-105151086CCUAGCACUUUGGGAGGCCA1201
54790_1_1023+chr4: 105151083-105151103CCAAGGUGAGAGAUCACUUG1202
54790_1_1025+chr4: 105151088-105151108GUGAGAGAUCACUUGAGGCC1203
54790_1_1030+chr4: 105151106-105151126CCAGGAGUUUGAAACCACCC1204
54790_1_1031+chr4: 105151107-105151127CAGGAGUUUGAAACCACCCU1205
54790_1_1034+chr4: 105151120-105151140CCACCCUGGGCAACACAGUC1206
54790_1_1037+chr4: 105151155-105151175CAAAAAAUUUAAAAAGUUAG1207
54790_1_1038+chr4: 105151156-105151176AAAAAAUUUAAAAAGUUAGU1208
54790_1_1039+chr4: 105151157-105151177AAAAAUUUAAAAAGUUAGUG1209
54790_1_1040+chr4: 105151162-105151182UUUAAAAAGUUAGUGGGGCA1210
54790_1_1041+chr4: 105151165-105151185AAAAAGUUAGUGGGGCAUGG1211
54790_1_1046+chr4: 105151193-105151213UCCUGUAGUCCCAGCUACUC1212
54790_1_1051+chr4: 105151206-105151226GCUACUCAGGAGACUGAGAU1213
54790_1_1054+chr4: 105151209-105151229ACUCAGGAGACUGAGAUAGG1214
54790_1_1056+chr4: 105151213-105151233AGGAGACUGAGAUAGGAGGA1215
54790_1_1062+chr4: 105151275-105151295ACACCACUGCGCUCCAGCCC1216
54790_1_1066+chr4: 105151282-105151302UGCGCUCCAGCCCAGGCAAG1217
54790_1_1068+chr4: 105151283-105151303GCGCUCCAGCCCAGGCAAGA1218
54790_1_1085+chr4: 105151426-105151446AAAAAGAAGAAACAGAUAGU1219
54790_1_1088+chr4: 105151429-105151449AAGAAGAAACAGAUAGUAGG1220
54790_1_1100+chr4: 105151548-105151568GUUUUAAGAAUUCAGAACUC1221
54790_1_1102+chr4: 105151553-105151573AAGAAUUCAGAACUCAGGCC1222
54790_1_1105+chr4: 105151558-105151578UUCAGAACUCAGGCCAGGUG1223
54790_1_1106+chr4: 105151561-105151581AGAACUCAGGCCAGGUGUGG1224
54790_1_1110+chr4: 105151571-105151591CCAGGUGUGGUGGCUCAUUC1225
54790_1_1112+chr4: 105151572-105151592CAGGUGUGGUGGCUCAUUCU1226
54790_1_1114+chr4: 105151575-105151595GUGUGGUGGCUCAUUCUGGG1227
54790_1_1116+chr4: 105151576-105151596UGUGGUGGCUCAUUCUGGGA1228
54790_1_1119+chr4: 105151577-105151597GUGGUGGCUCAUUCUGGGAG1229
54790_1_1120+chr4: 105151581-105151601UGGCUCAUUCUGGGAGGGGA1230
54790_1_1123+chr4: 105151585-105151605UCAUUCUGGGAGGGGAAGGC1231
54790_1_1125+chr4: 105151588-105151608UUCUGGGAGGGGAAGGCAGG1232
54790_1_1128+chr4: 105151599-105151619GAAGGCAGGAGGAUCACUUG1233
54790_1_1132+chr4: 105151622-105151642CCAGAAGUUCUAGACCAGCC1234
54790_1_1133+chr4: 105151623-105151643CAGAAGUUCUAGACCAGCCU1235
54790_1_1152+chr4: 105151771-105151791GAGAAUUAAAGUAAGAGACG1236
54790_1_1153+chr4: 105151775-105151795AUUAAAGUAAGAGACGAGGC1237
54790_1_1155+chr4: 105151781-105151801GUAAGAGACGAGGCCGGUUG1238
54790_1_1156+chr4: 105151784-105151804AGAGACGAGGCCGGUUGUGG1239
54790_1_1160+chr4: 105151811-105151831UGCCUGUAAUCCCAGCACUU1240
54790_1_1161+chr4: 105151812-105151832GCCUGUAAUCCCAGCACUUU1241
54790_1_1162+chr4: 105151821-105151841CCCAGCACUUUGGGACGACA1242
54790_1_1163+chr4: 105151825-105151845GCACUUUGGGACGACAAGGC1243
54790_1_1165+chr4: 105151828-105151848CUUUGGGACGACAAGGCAGG1244
54790_1_1169+chr4: 105151839-105151859CAAGGCAGGUGGAUGACCUG1245
54790_1_1171+chr4: 105151844-105151864CAGGUGGAUGACCUGAGGUC1246
54790_1_1174+chr4: 105151862-105151882UCAGGAGUUUGAGACCAGCC1247
54790_1_1175+chr4: 105151871-105151891UGAGACCAGCCUGGCCAACA1248
54790_1_1180+chr4: 105151910-105151930CUAAAAAUACAAAAAUUAGC1249
54790_1_1181+chr4: 105151911-105151931UAAAAAUACAAAAAUUAGCC1250
54790_1_1182+chr4: 105151916-105151936AUACAAAAAUUAGCCGGGCA1251
54790_1_1183+chr4: 105151919-105151939CAAAAAUUAGCCGGGCAUGG1252
54790_1_1187+chr4: 105151947-105151967ACCAGUAAUCCCAGCUACUC1253
54790_1_1188+chr4: 105151950-105151970AGUAAUCCCAGCUACUCAGG1254
54790_1_1190+chr4: 105151956-105151976CCCAGCUACUCAGGAGGCUG1255
54790_1_1196+chr4: 105151978-105151998GCCCGAGAAUCACUUGAGCC1256
54790_1_1197+chr4: 105151979-105151999CCCGAGAAUCACUUGAGCCU1257
54790_1_1198+chr4: 105151984-105152004GAAUCACUUGAGCCUGGGCA1258
54790_1_1199+chr4: 105151987-105152007UCACUUGAGCCUGGGCAUGG1259
54790_1_1203+chr4: 105152014-105152034UACCUAUAAUCCCAGCACUU1260
54790_1_1204+chr4: 105152015-105152035ACCUAUAAUCCCAGCACUUU1261
54790_1_1206+chr4: 105152018-105152038UAUAAUCCCAGCACUUUGGG1262
54790_1_1208+chr4: 105152024-105152044CCCAGCACUUUGGGAGGCCG1263
54790_1_1209+chr4: 105152028-105152048GCACUUUGGGAGGCCGAGGC1264
54790_1_1211+chr4: 105152031-105152051CUUUGGGAGGCCGAGGCAGG1265
54790_1_1215+chr4: 105152047-105152067CAGGUGGAUCACCUGACGUC1266
54790_1_1218+chr4: 105152065-105152085UCAGGAAUUCGAGACCAGUC1267
54790_1_1219+chr4: 105152074-105152094CGAGACCAGUCUGGCCAACA1268
54790_1_1223+chr4: 105152112-105152132ACUAAACAUACAAAAUUAGC1269
54790_1_1224+chr4: 105152113-105152133CUAAACAUACAAAAUUAGCU1270
54790_1_1225+chr4: 105152118-105152138CAUACAAAAUUAGCUGGGUG1271
54790_1_1226+chr4: 105152121-105152141ACAAAAUUAGCUGGGUGUGG1272
54790_1_1229+chr4: 105152149-105152169GCCUGUAGUCUCAGCUAUUC1273
54790_1_1231+chr4: 105152152-105152172UGUAGUCUCAGCUAUUCUGG1274
54790_1_1234+chr4: 105152162-105152182GCUAUUCUGGAGGCUGAUAC1275
54790_1_1241+chr4: 105152184-105152204GAGAAUUGCUUGAACCCUCC1276
54790_1_1243+chr4: 105152185-105152205AGAAUUGCUUGAACCCUCCC1277
54790_1_1244+chr4: 105152188-105152208AUUGCUUGAACCCUCCCGGG1278
54790_1_1247+chr4: 105152194-105152214UGAACCCUCCCGGGAGGCAG1279
54790_1_1249+chr4: 105152200-105152220CUCCCGGGAGGCAGAGGCUG1280
54790_1_1252+chr4: 105152213-105152233GAGGCUGCGGUGAGCCGAGA1281
54790_1_1254+chr4: 105152234-105152254GGCUCUGCUGCACUCCAGCC1282
54790_1_1255+chr4: 105152235-105152255GCUCUGCUGCACUCCAGCCU1283
54790_1_1257+chr4: 105152240-105152260GCUGCACUCCAGCCUGGGCG1284
54790_1_1263+chr4: 105152287-105152307GAAAAAUAAUAAUAAUAAAU1285
54790_1_1267+chr4: 105152302-105152322UAAAUAGGAGAUGAAUAAAU1286
54790_1_1269+chr4: 105152303-105152323AAAUAGGAGAUGAAUAAAUU1287
54790_1_1272+chr4: 105152321-105152341UUGGGAUAAAGUGUUUUUGA1288
54790_1_1275+chr4: 105152331-105152351GUGUUUUUGAAGGACAGUCU1289
54790_1_1281+chr4: 105152347-105152367GUCUAGGAUAUAAAAUGAAC1290
54790_1_1290+chr4: 105152408-105152428UACAUUUCUUUUUUGUCUAU1291
54790_1_1293+chr4: 105152412-105152432UUUCUUUUUUGUCUAUUGGA1292
54790_1_1296+chr4: 105152416-105152436UUUUUUGUCUAUUGGAAGGU1293
54790_1_1310+chr4: 105152484-105152504ACCUCUCAGUCAAUAUUUAA1294
54790_1_1339+chr4: 105152599-105152619UUUUUUUUUUUUUUUUGAGA1295
54790_1_1356+chr4: 105152620-105152640GGUAUCUUGCUCUGUCACCU1296
54790_1_1359+chr4: 105152624-105152644UCUUGCUCUGUCACCUAGGC1297
54790_1_1361+chr4: 105152634-105152654UCACCUAGGCUGGAGUGCAG1298
54790_1_1362+chr4: 105152645-105152665GGAGUGCAGUGGUGUGAUCU1299
54790_1_1363+chr4: 105152670-105152690CACUGCAACCUCUGCCUUCC1300
54790_1_1369+chr4: 105152708-105152728UUCUCAGCCCCCAGAGUAGC1301
54790_1_1371+chr4: 105152709-105152729UCUCAGCCCCCAGAGUAGCU1302
54790_1_1375+chr4: 105152715-105152735CCCCCAGAGUAGCUGGGACU1303
54790_1_1377+chr4: 105152736-105152756GGAGCGUGCCCCACCACACC1304
54790_1_1380+chr4: 105152765-105152785UUUCUAUUUUUAUUAGAGAC1305
54790_1_1381+chr4: 105152766-105152786UUCUAUUUUUAUUAGAGACA1306
54790_1_1390+chr4: 105152780-105152800GAGACAGGGUUUCACCAUGU1307
54790_1_1392+chr4: 105152785-105152805AGGGUUUCACCAUGUUGGCC1308
54790_1_1396+chr4: 105152803-105152823CCAGGCUGAUCUCGUACUCC1309
54790_1_1397+chr4: 105152810-105152830GAUCUCGUACUCCUGGUCUC1310
54790_1_1399+chr4: 105152826-105152846UCUCAGGUGAUCUGCCUGCC1311
54790_1_1400+chr4: 105152827-105152847CUCAGGUGAUCUGCCUGCCC1312
54790_1_1402+chr4: 105152843-105152863GCCCGGGUCUCCCAAAGUGC1313
54790_1_1404+chr4: 105152844-105152864CCCGGGUCUCCCAAAGUGCU1314
54790_1_1405+chr4: 105152852-105152872UCCCAAAGUGCUGGGAUUAC1315
54790_1_1407+chr4: 105152871-105152891CAGGCAUGAGCCACUGCACC1316
54790_1_1415+chr4: 105152920-105152940AAAAAUAGUGUUAAGUGUCU1317
54790_1_1416+chr4: 105152926-105152946AGUGUUAAGUGUCUUGGUGA1318
54790_1_1418+chr4: 105152935-105152955UGUCUUGGUGAUGGUGAUGA1319
54790_1_1421+chr4: 105152939-105152959UUGGUGAUGGUGAUGAUGGU1320
54790_1_1423+chr4: 105152947-105152967GGUGAUGAUGGUAGGAGUAA1321
54790_1_1424+chr4: 105152977-105152997UCCUUACAUUUAAUUUCUAC1322
54790_1_1428+chr4: 105152983-105153003CAUUUAAUUUCUACAGGCUA1323
54790_1_1436+chr4: 105153029-105153049AUUUUAAGCACAAAAGUGAA1324
54790_1_1442+chr4: 105153049-105153069UGGUUUUUAGUAAACUUAUA1325
54790_1_1443+chr4: 105153050-105153070GGUUUUUAGUAAACUUAUAU1326
54790_1_1469+chr4: 105153160-105153180ACUUGCUCAAUUUCCCCCAG1327
54790_1_1475+chr4: 105153247-105153267CCAUGAUACUGACAUUGAUG1328
54790_1_1526+chr4: 105153484-105153504AAGUCCUUUUUUUGAUAGAA1329
54790_1_1546+chr4: 105153567-105153587CUCAUCACAACCCUAGAGAU1330
54790_1_1553+chr4: 105153597-105153617CUUAUCCCUAUUUAUGAGUG1331
54790_1_1560+chr4: 105153616-105153636GAGGAAACUGAAGCCCAGUG1332
54790_1_1563+chr4: 105153654-105153674AAGUUCAUACAGCCUAUACA1333
54790_1_1565+chr4: 105153660-105153680AUACAGCCUAUACAUGGCUU1334
54790_1_1581+chr4: 105153766-105153786AGCUGUAAAAGUGUAUAAUG1335
54790_1_1587+chr4: 105153791-105153811UAUGUAGAGAAAGUCAUAAA1336
54790_1_1594+chr4: 105153864-105153884CAUUACAGCAUUAUUAAUAA1337
54790_1_1599+chr4: 105153874-105153894UUAUUAAUAAUGGUAAAAAA1338
54790_1_1604+chr4: 105153922-105153942AUGAGUGAAUAAACAAAUUG1339
54790_1_1609+chr4: 105153961-105153981AAUAUUAUUAAGUAGUAUAA1340
54790_1_1611+chr4: 105153966-105153986UAUUAAGUAGUAUAAAGGAA1341
54790_1_1614+chr4: 105153992-105154012AUUGAUAAAUGCUGUCACAU1342
54790_1_1620+chr4: 105154005-105154025GUCACAUAGGUGAAUCUGAG1343
54790_1_1623+chr4: 105154016-105154036GAAUCUGAGAGGCACAAGAA1344
54790_1_1628+chr4: 105154060-105154080UUUUAAGUAACGUCCAGAAU1345
54790_1_1633+chr4: 105154071-105154091GUCCAGAAUAGGCAAAUCUA1346
54790_1_1637+chr4: 105154085-105154105AAUCUAAGGAGACAGAAAGU1347
54790_1_1639+chr4: 105154100-105154120AAAGUUGGCUAGUUAUUACU1348
54790_1_1641+chr4: 105154101-105154121AAGUUGGCUAGUUAUUACUA1349
54790_1_1642+chr4: 105154102-105154122AGUUGGCUAGUUAUUACUAG1350
54790_1_1646+chr4: 105154107-105154127GCUAGUUAUUACUAGGGGCU1351
54790_1_1647+chr4: 105154108-105154128CUAGUUAUUACUAGGGGCUA1352
54790_1_1650+chr4: 105154112-105154132UUAUUACUAGGGGCUAGGGA1353
54790_1_1651+chr4: 105154113-105154133UAUUACUAGGGGCUAGGGAU1354
54790_1_1655+chr4: 105154116-105154136UACUAGGGGCUAGGGAUGGG1355
54790_1_1657+chr4: 105154117-105154137ACUAGGGGCUAGGGAUGGGA1356
54790_1_1660+chr4: 105154120-105154140AGGGGCUAGGGAUGGGAGGG1357
54790_1_1662+chr4: 105154151-105154171AAUAAGUAUGAGAUUUCUUU1358
54790_1_1678+chr4: 105154240-105154260ACUGAAUUAUAUGCUUUAAA1359
54790_1_1694+chr4: 105154312-105154332AUGAAUGUAGUUGAGUUAUU1360
54790_1_1711+chr4: 105154362-105154382AUCUCAUGCAAAAGAAAUGC1361
54790_1_1713+chr4: 105154372-105154392AAAGAAAUGCAGGAACUAUU1362
54790_1_1716+chr4: 105154383-105154403GGAACUAUUUGGAUUGAAUG1363
54790_1_1721+chr4: 105154402-105154422GAGGCUAAGCAUAUCUUUCU1364
54790_1_1723+chr4: 105154409-105154429AGCAUAUCUUUCUAGGAAGA1365
54790_1_1726+chr4: 105154417-105154437UUUCUAGGAAGAUGGCAUCA1366
54790_1_1729+chr4: 105154442-105154462UUUUAUUAUGCCUGUAAUCC1367
54790_1_1734+chr4: 105154450-105154470UGCCUGUAAUCCUGGCACUU1368
54790_1_1738+chr4: 105154451-105154471GCCUGUAAUCCUGGCACUUU1369
54790_1_1739+chr4: 105154454-105154474UGUAAUCCUGGCACUUUGGG1370
54790_1_1740+chr4: 105154460-105154480CCUGGCACUUUGGGAGGCCA1371
54790_1_1743+chr4: 105154463-105154483GGCACUUUGGGAGGCCAAGG1372
54790_1_1744+chr4: 105154464-105154484GCACUUUGGGAGGCCAAGGC1373
54790_1_1751+chr4: 105154490-105154510CCAGAAGUUUGAGAUUAGUC1374
54790_1_1752+chr4: 105154491-105154511CAGAAGUUUGAGAUUAGUCU1375
54790_1_1759+chr4: 105154516-105154536ACAUCCUCUUAUAGAUGAGA1376
54790_1_1761+chr4: 105154539-105154559AUACUUAAUCACUCAAAAGU1377
54790_1_1770+chr4: 105154581-105154601AAUAGCCUUUAGAGCUCAUA1378
54790_1_1773+chr4: 105154582-105154602AUAGCCUUUAGAGCUCAUAU1379
54790_1_1776+chr4: 105154605-105154625AAGAUUCAAUAGAUAGUGAU1380
54790_1_1778+chr4: 105154618-105154638UAGUGAUAGGUUAUAUGACU1381
54790_1_1781+chr4: 105154626-105154646GGUUAUAUGACUUGGUAAAG1382
54790_1_1782+chr4: 105154627-105154647GUUAUAUGACUUGGUAAAGA1383
54790_1_1785+chr4: 105154640-105154660GUAAAGAGGGCUUAAUGUAU1384
54790_1_1793+chr4: 105154690-105154710GUUACCUAGCCAUUCAGUUC1385
54790_1_1801+chr4: 105154714-105154734GAUGUAACCCAAGUGUUAAA1386
54790_1_1803+chr4: 105154725-105154745AGUGUUAAAAGGAAUGUGAC1387
54790_1_1804+chr4: 105154726-105154746GUGUUAAAAGGAAUGUGACU1388
54790_1_1805+chr4: 105154731-105154751AAAAGGAAUGUGACUGGGUG1389
54790_1_1807+chr4: 105154734-105154754AGGAAUGUGACUGGGUGCGG1390
54790_1_1809+chr4: 105154765-105154785UGUAAUCCCAGCACUUUGCG1391
54790_1_1811+chr4: 105154768-105154788AAUCCCAGCACUUUGCGAGG1392
54790_1_1814+chr4: 105154774-105154794AGCACUUUGCGAGGCGGAAG1393
54790_1_1815+chr4: 105154775-105154795GCACUUUGCGAGGCGGAAGU1394
54790_1_1817+chr4: 105154778-105154798CUUUGCGAGGCGGAAGUGGG1395
54790_1_1818+chr4: 105154779-105154799UUUGCGAGGCGGAAGUGGGU1396
54790_1_1824+chr4: 105154794-105154814UGGGUGGGUCUCUUGAGCUC1397
54790_1_1827+chr4: 105154800-105154820GGUCUCUUGAGCUCAGGAGU1398
54790_1_1830+chr4: 105154812-105154832UCAGGAGUUGGAGACAAGCC1399
54790_1_1831+chr4: 105154813-105154833CAGGAGUUGGAGACAAGCCU1400
54790_1_1832+chr4: 105154821-105154841GGAGACAAGCCUGGGCAACA1401
54790_1_1835+chr4: 105154860-105154880CAAAAAAUGCACAAAUUAGC1402
54790_1_1836+chr4: 105154861-105154881AAAAAAUGCACAAAUUAGCU1403
54790_1_1837+chr4: 105154866-105154886AUGCACAAAUUAGCUGGGUG1404
54790_1_1838+chr4: 105154869-105154889CACAAAUUAGCUGGGUGUGG1405
54790_1_1840+chr4: 105154889-105154909UGGCACAUCCCUGUAGUUCC1406
54790_1_1842+chr4: 105154898-105154918CCUGUAGUUCCAGGUACUUG1407
54790_1_1844+chr4: 105154899-105154919CUGUAGUUCCAGGUACUUGU1408
54790_1_1845+chr4: 105154900-105154920UGUAGUUCCAGGUACUUGUG1409
54790_1_1847+chr4: 105154906-105154926UCCAGGUACUUGUGGGGCUG1410
54790_1_1850+chr4: 105154909-105154929AGGUACUUGUGGGGCUGAGG1411
54790_1_1853+chr4: 105154910-105154930GGUACUUGUGGGGCUGAGGC1412
54790_1_1855+chr4: 105154913-105154933ACUUGUGGGGCUGAGGCGGG1413
54790_1_1856+chr4: 105154917-105154937GUGGGGCUGAGGCGGGAGGA1414
54790_1_1861+chr4: 105154928-105154948GCGGGAGGAUGGCUCGAGCC1415
54790_1_1862+chr4: 105154929-105154949CGGGAGGAUGGCUCGAGCCU1416
54790_1_1865+chr4: 105154938-105154958GGCUCGAGCCUGGGAAGUUG1417
54790_1_1867+chr4: 105154957-105154977GAGGCUGCAGUGAGCCAUGU1418
54790_1_1870+chr4: 105154978-105154998GGUGCCCCCACACUUCAGCC1419
54790_1_1871+chr4: 105154979-105154999GUGCCCCCACACUUCAGCCU1420
54790_1_1887+chr4: 105155091-105155111UAAUAACAAAUUACUAGAUU1421
54790_1_1889+chr4: 105155092-105155112AAUAACAAAUUACUAGAUUU1422
54790_1_1890+chr4: 105155093-105155113AUAACAAAUUACUAGAUUUG1423
54790_1_1892+chr4: 105155094-105155114UAACAAAUUACUAGAUUUGG1424
54790_1_1893+chr4: 105155095-105155115AACAAAUUACUAGAUUUGGG1425
54790_1_1902+chr4: 105155128-105155148CUUAUCUAUGUGAAAACAGA1426
54790_1_1903+chr4: 105155129-105155149UUAUCUAUGUGAAAACAGAA1427
54790_1_1906+chr4: 105155138-105155158UGAAAACAGAAGGGCAAUGC1428
54790_1_1907+chr4: 105155139-105155159GAAAACAGAAGGGCAAUGCA1429
54790_1_1927+chr4: 105155237-105155257AAAAUGACAAAGUAUCUCAU1430
54790_1_1928+chr4: 105155238-105155258AAAUGACAAAGUAUCUCAUA1431
54790_1_1932+chr4: 105155278-105155298UUUCCUGUUAACUGAUACUG1432
54790_1_1938+chr4: 105155301-105155321CAUGUUGAAGAUGUAAAAUA1433
54790_1_1943+chr4: 105155310-105155330GAUGUAAAAUAAGGUUGAAA1434
54790_1_1948+chr4: 105155343-105155363GCAGCAGUCUUCAUAAUGCC1435
54790_1_1955+chr4: 105155360-105155380GCCAGGACAAAGUGAGAAAC1436
54790_1_1956+chr4: 105155361-105155381CCAGGACAAAGUGAGAAACA1437
54790_1_1959+chr4: 105155376-105155396AAACAGGGUCAGAAUGAUGA1438
54790_1_1960+chr4: 105155399-105155419CUCUCCAUCUUUGCUACACA1439
54790_1_1966+chr4: 105155448-105155468AACUUCUACAAACCACUUAC1440
54790_1_1972+chr4: 105155485-105155505AUUUUUAACACUAGUCCCUA1441
54790_1_1978+chr4: 105155506-105155526GGAACUAUGACUUGUAGUUU1442
54790_1_1980+chr4: 105155515-105155535ACUUGUAGUUUUGGACACAC1443
54790_1_1981+chr4: 105155516-105155536CUUGUAGUUUUGGACACACA1444
54790_1_1989+chr4: 105155528-105155548GACACACAGGGUGAAUUACU1445
54790_1_1990+chr4: 105155529-105155549ACACACAGGGUGAAUUACUU1446
54790_1_1991+chr4: 105155530-105155550CACACAGGGUGAAUUACUUG1447
54790_1_2011+chr4: 105155628-105155648UUUUAUUCUCAUGAGAAUGC1448
54790_1_2012+chr4: 105155629-105155649UUUAUUCUCAUGAGAAUGCU1449
54790_1_2018+chr4: 105155639-105155659UGAGAAUGCUGGGUUGCAGC1450
54790_1_2020+chr4: 105155643-105155663AAUGCUGGGUUGCAGCCGGU1451
54790_1_2024+chr4: 105155657-105155677GCCGGUUGGAUCCCAUACCU1452
54790_1_2025+chr4: 105155658-105155678CCGGUUGGAUCCCAUACCUU1453
54790_1_2028+chr4: 105155676-105155696UUGGGACCAUGACUGAUAAC1454
54790_1_2033+chr4: 105155681-105155701ACCAUGACUGAUAACUGGAG1455
54790_1_2038+chr4: 105155700-105155720GUGGAGAAAAUUCACUGAUC1456
54790_1_2039+chr4: 105155705-105155725GAAAAUUCACUGAUCUGGAA1457
54790_1_2043+chr4: 105155717-105155737AUCUGGAAAGGUUGAGCUUU1458
54790_1_2044+chr4: 105155718-105155738UCUGGAAAGGUUGAGCUUUA1459
54790_1_2047+chr4: 105155737-105155757AGGGUUCAGAGACUUAUUUA1460
54790_1_2055+chr4: 105155763-105155783ACAUGUGAUUGUACCCAAUA1461
54790_1_2058+chr4: 105155774-105155794UACCCAAUAAGGAAGUAUAU1462
54790_1_2077+chr4: 105155861-105155881UGAUCAUAGCAUCUACUUGU1463
54790_1_2086+chr4: 105155923-105155943UGUUAGACCCAUUAAGAAGU1464
54790_1_2088+chr4: 105155934-105155954UUAAGAAGUUGGUGUAGUGA1465
54790_1_2092+chr4: 105155940-105155960AGUUGGUGUAGUGAUGGUUA1466
54790_1_2097+chr4: 105155963-105155983AAAGCAGUAAGAUAGAAUUU1467
54790_1_2100+chr4: 105155981-105156001UUAGGUUCUGUUCUCCUUAC1468
54790_1_2138+chr4: 105156175-105156195UAAAUCUGUUCUCGCAUAUU1469
54790_1_2158+chr4: 105156235-105156255UUAUAAGUAAUUUAUACAGA1470
54790_1_2168+chr4: 105156263-105156283CAUAUUCAAAAGAAGAAAAA1471
54790_1_2169+chr4: 105156264-105156284AUAUUCAAAAGAAGAAAAAU1472
54790_1_2178+chr4: 105156301-105156321UGAUGUACUACUCUCUUCAA1473
54790_1_2180+chr4: 105156302-105156322GAUGUACUACUCUCUUCAAA1474
54790_1_2181+chr4: 105156319-105156339AAAGGGAAUUGCCUAUGUUC1475
54790_1_2186+chr4: 105156333-105156353AUGUUCAGGCAUAGAAAUGC1476
54790_1_2188+chr4: 105156349-105156369AUGCAGGCAGUCUGACAUUU1477
54790_1_2207+chr4: 105156424-105156444AUUUGUCACAGUUUGUUCUG1478
54790_1_2208+chr4: 105156425-105156445UUUGUCACAGUUUGUUCUGU1479
54790_1_2210+chr4: 105156428-105156448GUCACAGUUUGUUCUGUGGG1480
54790_1_2213+chr4: 105156429-105156449UCACAGUUUGUUCUGUGGGU1481
54790_1_2216+chr4: 105156441-105156461CUGUGGGUGGGUAAAAGUAA1482
54790_1_2231+chr4: 105156546-105156566UAAAUCUAGCUUCUAUGUCC1483
54790_1_2239+chr4: 105156585-105156605ACAUUCACCCAUCUCUCAAA1484
54790_1_2240+chr4: 105156586-105156606CAUUCACCCAUCUCUCAAAU1485
54790_1_2249+chr4: 105156649-105156669AAAAGUAAAAAAGCUUCAAU1486
54790_1_2251+chr4: 105156650-105156670AAAGUAAAAAAGCUUCAAUA1487
54790_1_2254+chr4: 105156678-105156698GAAAGCCAGAUAACAUAGCA1488
54790_1_2262+chr4: 105156726-105156746CUUACCUGUCUGCACUAAGA1489
54790_1_2265+chr4: 105156727-105156747UUACCUGUCUGCACUAAGAA1490
54790_1_2278+chr4: 105156840-105156860CUAUCCAUAACAUACUGUCC1491
54790_1_2310+chr4: 105156941-105156961AGAAUUUUUAUAUUUGCCAU1492
54790_1_2323+chr4: 105156995-105157015UUCAUUAUAUUUGCAUUAAA1493
54790_1_2373+chr4: 105157234-105157254GAAAAGAAGAAUACCAUAAA1494
54790_1_2374+chr4: 105157235-105157255AAAAGAAGAAUACCAUAAAU1495
54790_1_2378+chr4: 105157254-105157274UGGGUACCUUUCAAAAAUGA1496
54790_1_2394+chr4: 105157346-105157366ACAAACAGAUACAUUUUAGC1497
54790_1_2411+chr4: 105157411-105157431UUCCAAUCUAGCCACUGAAA1498
54790_1_2422+chr4: 105157463-105157483CAUAAGUUGAAUUUAAAACA1499
54790_1_2435+chr4: 105157506-105157526UGUCUGCCACAUUACGCUUG1500
54790_1_2437+chr4: 105157517-105157537UUACGCUUGUGGAAAAACAC1501
54790_1_2442+chr4: 105157551-105157571GCUAAUAGACAUUUUGCUGU1502
54790_1_2446+chr4: 105157567-105157587CUGUUGGCUCACCUUAUUAA1503
54790_1_2457+chr4: 105157621-105157641GCAAACUUGAAAAAGACGUU1504
54790_1_2461+chr4: 105157634-105157654AGACGUUUGGUUACUAACUG1505
54790_1_2463+chr4: 105157635-105157655GACGUUUGGUUACUAACUGU1506
54790_1_2471+chr4: 105157675-105157695UAUUUUUAUUUUUUAUUUUU1507
54790_1_2489+chr4: 105157699-105157719AGAGUCUCACUCUCUUGCCC1508
54790_1_2492+chr4: 105157703-105157723UCUCACUCUCUUGCCCAGGC1509
54790_1_2493+chr4: 105157713-105157733UUGCCCAGGCUGGAGUGCAG1510
54790_1_2495+chr4: 105157724-105157744GGAGUGCAGUGGCAUGAUCU1511
54790_1_2498+chr4: 105157748-105157768UCACUGCAGCCUCCUCCUUC1512
54790_1_2499+chr4: 105157749-105157769CACUGCAGCCUCCUCCUUCU1513
54790_1_2505+chr4: 105157788-105157808GUCUCAGCCUCCCGAGUAGC1514
54790_1_2507+chr4: 105157789-105157809UCUCAGCCUCCCGAGUAGCU1515
54790_1_2508+chr4: 105157797-105157817UCCCGAGUAGCUGGGAUUAU1516
54790_1_2510+chr4: 105157816-105157836UAGGCACCAGCCACCAUGCC1517
54790_1_2521+chr4: 105157860-105157880GAAACAGCGUUUCGCCAUGU1518
54790_1_2522+chr4: 105157865-105157885AGCGUUUCGCCAUGUAGGCU1519
54790_1_2523+chr4: 105157869-105157889UUUCGCCAUGUAGGCUAGGC1520
54790_1_2529+chr4: 105157923-105157943CCUUCUGCUUCCUAAAGUGC1521
54790_1_2530+chr4: 105157924-105157944CUUCUGCUUCCUAAAGUGCU1522
54790_1_2532+chr4: 105157932-105157952UCCUAAAGUGCUGGGAUUAC1523
54790_1_2535+chr4: 105157945-105157965GGAUUACAGGCAUGAGCCAU1524
54790_1_2536+chr4: 105157950-105157970ACAGGCAUGAGCCAUCGGCC1525
54790_1_2547+chr4: 105158014-105158034UUAUUUACUGUUAAAAAAUG1526
54790_1_2553+chr4: 105158040-105158060UUAUUUCAAAUAAGAUUUUA1527
54790_1_2574+chr4: 105158110-105158130ACCAACAUUUUUCAAGAGCA1528
54790_1_2578+chr4: 105158111-105158131CCAACAUUUUUCAAGAGCAU1529
54790_1_2582+chr4: 105158120-105158140UUCAAGAGCAUGGGAAAUCU1530
54790_1_2584+chr4: 105158121-105158141UCAAGAGCAUGGGAAAUCUA1531
54790_1_2587+chr4: 105158126-105158146AGCAUGGGAAAUCUAGGGUA1532
54790_1_2592+chr4: 105158158-105158178GUGACUUUAAAGACACUUCU1533
54790_1_2593+chr4: 105158159-105158179UGACUUUAAAGACACUUCUU1534
54790_1_2630+chr4: 105158269-105158289AUUAGUCAUGCCUUAAUCCU1535
54790_1_2631+chr4: 105158270-105158290UUAGUCAUGCCUUAAUCCUC1536
54790_1_2632+chr4: 105158271-105158291UAGUCAUGCCUUAAUCCUCG1537
54790_1_2635+chr4: 105158278-105158298GCCUUAAUCCUCGGGGUUUU1538
54790_1_2638+chr4: 105158279-105158299CCUUAAUCCUCGGGGUUUUU1539
54790_1_2642+chr4: 105158293-105158313GUUUUUGGGAAACUAUAUUU1540
54790_1_2643+chr4: 105158294-105158314UUUUUGGGAAACUAUAUUUA1541
54790_1_2644+chr4: 105158295-105158315UUUUGGGAAACUAUAUUUAG1542
54790_1_2655+chr4: 105158338-105158358AUUGUAAUUUUUCUCAGUAU1543
54790_1_2662+chr4: 105158350-105158370CUCAGUAUUGGUAAGAAUUC1544
54790_1_2665+chr4: 105158359-105158379GGUAAGAAUUCAGGUGUUUA1545
54790_1_2669+chr4: 105158364-105158384GAAUUCAGGUGUUUAAGGAA1546
54790_1_2684+chr4: 105158424-105158444GAUAUAAUGAAUGUAGAUGA1547
54790_1_2688+chr4: 105158440-105158460AUGAAGGUGAAAUCCGAGAU1548
54790_1_2692+chr4: 105158448-105158468GAAAUCCGAGAUAGGAAGAG1549
54790_1_2695+chr4: 105158480-105158500ACUUUUUUUUCCUUCACCCA1550
54790_1_2707+chr4: 105158502-105158522GAAAGCCAUUGAAUACUGAA1551
54790_1_2708+chr4: 105158503-105158523AAAGCCAUUGAAUACUGAAU1552
54790_1_2711+chr4: 105158523-105158543GGGUCAUGUUGUAAUUUAAU1553
54790_1_2712+chr4: 105158524-105158544GGUCAUGUUGUAAUUUAAUU1554
54790_1_2721+chr4: 105158574-105158594GCCUACUUAGUGUAUAUCUC1555
54790_1_2734+chr4: 105158635-105158655ACUGAAGUAAAUAAGCAAGC1556
54790_1_2738+chr4: 105158656-105158676GGAAUAAGUCCUGCAAAUAG1557
54790_1_2748+chr4: 105158719-105158739AACUGAUCCUAAAUUGAAUU1558
54790_1_2756+chr4: 105158756-105158776UAGAUUACAAGAAAUGCAAC1559
54790_1_2762+chr4: 105158788-105158808UUACAGUUCUUCCUCUUUUU1560
54790_1_2780+chr4: 105158868-105158888ACAUCUGUAUGCUCAUUUUU1561
54790_1_2782+chr4: 105158869-105158889CAUCUGUAUGCUCAUUUUUA1562
54790_1_2783+chr4: 105158884-105158904UUUUAGGGCCAAAAAAUAGU1563
54790_1_2789+chr4: 105158895-105158915AAAAAUAGUAGGCUUCUCUU1564
54790_1_2795+chr4: 105158933-105158953UCUCUCCUUCCAGUUACACG1565
54790_1_2801+chr4: 105158956-105158976UCACAUCAACAUUUGACACG1566
54790_1_2802+chr4: 105158957-105158977CACAUCAACAUUUGACACGU1567
54790_1_2804+chr4: 105158971-105158991ACACGUGGGUACCGUGCACG1568
54790_1_2807+chr4: 105158999-105159019GUAUUUACAAACACCAUCCU1569
54790_1_2814+chr4: 105159026-105159046CAGAGACUCUUAUGUAACAG1570
54790_1_2820+chr4: 105159052-105159072GAGUAAGCUUUGAGUGUCUG1571
54790_1_2821+chr4: 105159053-105159073AGUAAGCUUUGAGUGUCUGU1572
54790_1_2824+chr4: 105159056-105159076AAGCUUUGAGUGUCUGUGGG1573
54790_1_2827+chr4: 105159059-105159079CUUUGAGUGUCUGUGGGCGG1574
54790_1_2832+chr4: 105159087-105159107ACACAGUUUAAUUCAUUGUC1575
54790_1_2834+chr4: 105159088-105159108CACAGUUUAAUUCAUUGUCC1576
54790_1_2837+chr4: 105159101-105159121AUUGUCCGGGAGCCCUUGUC1577
54790_1_2841+chr4: 105159111-105159131AGCCCUUGUCUGGCUCUGAU1578
54790_1_2842+chr4: 105159112-105159132GCCCUUGUCUGGCUCUGAUA1579
54790_1_2845+chr4: 105159132-105159152GGGUCAUGAACCAAAGAUCA1580
54790_1_2846+chr4: 105159140-105159160AACCAAAGAUCAAGGUGUUU1581
54790_1_2848+chr4: 105159145-105159165AAGAUCAAGGUGUUUAGGUC1582
54790_1_2851+chr4: 105159163-105159183UCAGGAUAUUCCCUAACGCA1583
54790_1_2870+chr4: 105159253-105159273UUUUUUUUUUUUUUUUGAGA1584
54790_1_2888+chr4: 105159275-105159295GAGUUUCGCUCUUGCUGCCA1585
54790_1_2891+chr4: 105159279-105159299UUCGCUCUUGCUGCCAAGGU1586
54790_1_2895+chr4: 105159289-105159309CUGCCAAGGUUGGAGUGCAG1587
54790_1_2897+chr4: 105159303-105159323GUGCAGUGGCGCCGCGAUCU1588
54790_1_2898+chr4: 105159328-105159348CACUGCAACCUCCGCCUCAC1589
54790_1_2903+chr4: 105159367-105159387GCCUCAGACACCCAAGUAGC1590
54790_1_2904+chr4: 105159368-105159388CCUCAGACACCCAAGUAGCU1591
54790_1_2905+chr4: 105159376-105159396ACCCAAGUAGCUGGGAUUAU1592
54790_1_2907+chr4: 105159395-105159415UAGGCAUGCGCCACCACGCC1593
54790_1_2910+chr4: 105159422-105159442UUUUGUAUUUUUAGUACAGA1594
54790_1_2911+chr4: 105159423-105159443UUUGUAUUUUUAGUACAGAC1595
54790_1_2912+chr4: 105159424-105159444UUGUAUUUUUAGUACAGACG1596
54790_1_2920+chr4: 105159438-105159458CAGACGGGGUUUCUCCAUGU1597
54790_1_2921+chr4: 105159447-105159467UUUCUCCAUGUUGGUCAGCC1598
54790_1_2926+chr4: 105159468-105159488GGUGUUGAACUCCCGACUUA1599
54790_1_2928+chr4: 105159485-105159505UUAAGGUGAUCCGCUUGCUU1600
54790_1_2932+chr4: 105159501-105159521GCUUCGGCCCCCCAAAGUGC1601
54790_1_2934+chr4: 105159502-105159522CUUCGGCCCCCCAAAGUGCU1602
54790_1_2936+chr4: 105159510-105159530CCCCAAAGUGCUGGGAUUAC1603
54790_1_2946+chr4: 105159595-105159615GCCAAACCAUUUUUGUGAUU1604
54790_1_2949+chr4: 105159596-105159616CCAAACCAUUUUUGUGAUUU1605
54790_1_2950+chr4: 105159597-105159617CAAACCAUUUUUGUGAUUUG1606
54790_1_2960+chr4: 105159621-105159641AACAUGAGCAGAUGAUGCUU1607
54790_1_2971+chr4: 105159716-105159736GCCUUUAAAAAAUUACAUCU1608
54790_1_2973+chr4: 105159721-105159741UAAAAAAUUACAUCUUGGCC1609
54790_1_2976+chr4: 105159725-105159745AAAUUACAUCUUGGCCAGGA1610
54790_1_2979+chr4: 105159744-105159764AUGGCUCACGCCUGUAAUCC1611
54790_1_2982+chr4: 105159752-105159772CGCCUGUAAUCCCGGCAUUU1612
54790_1_2983+chr4: 105159753-105159773GCCUGUAAUCCCGGCAUUUU1613
54790_1_2985+chr4: 105159756-105159776UGUAAUCCCGGCAUUUUGGG1614
54790_1_2986+chr4: 105159762-105159782CCCGGCAUUUUGGGAGGCCA1615
54790_1_2988+chr4: 105159765-105159785GGCAUUUUGGGAGGCCAAGG1616
54790_1_2989+chr4: 105159766-105159786GCAUUUUGGGAGGCCAAGGC1617
54790_1_2990+chr4: 105159769-105159789UUUUGGGAGGCCAAGGCGGG1618
54790_1_2996+chr4: 105159791-105159811GCAAGAGAUCGAGAUCAUCC1619
54790_1_2997+chr4: 105159800-105159820CGAGAUCAUCCUGGCCAACA1620
54790_1_3000+chr4: 105159839-105159859CUAAAAAUACAAAAAUUAGC1621
54790_1_3001+chr4: 105159840-105159860UAAAAAUACAAAAAUUAGCU1622
54790_1_3002+chr4: 105159845-105159865AUACAAAAAUUAGCUGGGCG1623
54790_1_3003+chr4: 105159848-105159868CAAAAAUUAGCUGGGCGUGG1624
54790_1_3005+chr4: 105159851-105159871AAAUUAGCUGGGCGUGGUGG1625
54790_1_3006+chr4: 105159852-105159872AAUUAGCUGGGCGUGGUGGC1626
54790_1_3010+chr4: 105159875-105159895CGCCUGUAAUCCCAGCUACU1627
54790_1_3011+chr4: 105159876-105159896GCCUGUAAUCCCAGCUACUU1628
54790_1_3013+chr4: 105159885-105159905CCCAGCUACUUGGGAGACUG1629
54790_1_3016+chr4: 105159889-105159909GCUACUUGGGAGACUGUGGC1630
54790_1_3021+chr4: 105159907-105159927GCAGGAGAAUCGCUUGACCC1631
54790_1_3023+chr4: 105159908-105159928CAGGAGAAUCGCUUGACCCC1632
54790_1_3025+chr4: 105159911-105159931GAGAAUCGCUUGACCCCGGG1633
54790_1_3027+chr4: 105159914-105159934AAUCGCUUGACCCCGGGAGG1634
54790_1_3029+chr4: 105159917-105159937CGCUUGACCCCGGGAGGCGG1635
54790_1_3034+chr4: 105159957-105159977CGCGCCACUGCACUCCAGCC1636
54790_1_3047+chr4: 105160057-105160077GAUUGACUUCCCAAACUAAA1637
54790_1_3054+chr4: 105160089-105160109AAAACACUCAAGAAAACUCU1638
54790_1_3071+chr4: 105160237-105160257AGCUUUAAGUCUCUAUAUUU1639
54790_1_3074+chr4: 105160238-105160258GCUUUAAGUCUCUAUAUUUA1640
54790_1_3095+chr4: 105160321-105160341GCAAGUUGAAAUAAAAAAAA1641
54790_1_3099+chr4: 105160357-105160377AAUGUCUAACCACGUAUAUU1642
54790_1_3100+chr4: 105160371-105160391UAUAUUUGGUAUAUGUAUAC1643
54790_1_3103+chr4: 105160399-105160419UGUAUUAGCUGUAAGCAGAC1644
54790_1_3117+chr4: 105160454-105160474UUCUUUUUGUAUUGCAUCUA1645
54790_1_3125+chr4: 105160468-105160488CAUCUAAGGAUCAUUUGAGA1646
54790_1_3155+chr4: 105160628-105160648UACACUACCUUUCUAAAGAU1647
54790_1_3163+chr4: 105160689-105160709AUAUGUAUUUUUUAAAAUAA1648
54790_1_3175+chr4: 105160733-105160753CAAGCACCAAAUCUGUUUUU1649
54790_1_3177+chr4: 105160734-105160754AAGCACCAAAUCUGUUUUUU1650
54790_1_3178+chr4: 105160735-105160755AGCACCAAAUCUGUUUUUUG1651
54790_1_3179+chr4: 105160736-105160756GCACCAAAUCUGUUUUUUGG1652
54790_1_3180+chr4: 105160744-105160764UCUGUUUUUUGGGGGUUUUU1653
54790_1_3182+chr4: 105160752-105160772UUGGGGGUUUUUUGGUUUGU1654
54790_1_3208+chr4: 105160799-105160819AGAGUCUCCCUCUGUCGCCC1655
54790_1_3211+chr4: 105160803-105160823UCUCCCUCUGUCGCCCAGGC1656
54790_1_3215+chr4: 105160813-105160833UCGCCCAGGCUGGAGUGAAG1657
54790_1_3217+chr4: 105160823-105160843UGGAGUGAAGCGGAGCGAUC1658
54790_1_3218+chr4: 105160824-105160844GGAGUGAAGCGGAGCGAUCU1659
54790_1_3220+chr4: 105160848-105160868UCACCGCAACCUCCGCCUCC1660
54790_1_3221+chr4: 105160849-105160869CACCGCAACCUCCGCCUCCU1661
54790_1_3222+chr4: 105160872-105160892UUCCAGCAAUUCUCUGCCUC1662
54790_1_3225+chr4: 105160878-105160898CAAUUCUCUGCCUCAGGCUU1663
54790_1_3230+chr4: 105160887-105160907GCCUCAGGCUUCGGAGUAGC1664
54790_1_3231+chr4: 105160888-105160908CCUCAGGCUUCGGAGUAGCU1665
54790_1_3232+chr4: 105160896-105160916UUCGGAGUAGCUGGGAUUAC1666
54790_1_3235+chr4: 105160915-105160935CAGGCACUCGCCACCACGCC1667
54790_1_3237+chr4: 105160940-105160960AAUUUUUGUAUUUUUAGUAG1668
54790_1_3239+chr4: 105160943-105160963UUUUGUAUUUUUAGUAGAGG1669
54790_1_3241+chr4: 105160944-105160964UUUGUAUUUUUAGUAGAGGC1670
54790_1_3243+chr4: 105160945-105160965UUGUAUUUUUAGUAGAGGCG1671
54790_1_3251+chr4: 105160959-105160979GAGGCGGGGUUUUACCAUCU1672
54790_1_3252+chr4: 105160964-105160984GGGGUUUUACCAUCUUGGUC1673
54790_1_3253+chr4: 105160968-105160988UUUUACCAUCUUGGUCAGGC1674
54790_1_3259+chr4: 105160987-105161007CUGGUUUUGAACUCCUGACC1675
54790_1_3264+chr4: 105161020-105161040GCCUCAGCCUCCCAAAGUGC1676
54790_1_3266+chr4: 105161021-105161041CCUCAGCCUCCCAAAGUGCU1677
54790_1_3267+chr4: 105161029-105161049UCCCAAAGUGCUGGGAUUAC1678
54790_1_3269+chr4: 105161053-105161073GUUUUUCUUUAAGUAAUACU1679
54790_1_3281+chr4: 105161075-105161095GUAUAAGAGAACUUUAUAUC1680
54790_1_3290+chr4: 105161128-105161148UUAUUCACAUAUAGAAACUC1681
54790_1_3301+chr4: 105161168-105161188CUAAAGCUGUUCUCAUUUAG1682
54790_1_3309+chr4: 105161214-105161234UUAACUAACAAUAAAAUCUA1683
54790_1_3320+chr4: 105161259-105161279GCAGAGCAAAAGCAGCCUUC1684
54790_1_3340+chr4: 105161348-105161368AAUUAAGAUGCGAUGAGAGU1685
54790_1_3354+chr4: 105161407-105161427UCUACUUGCUUUUUUAGUGU1686
54790_1_3361+chr4: 105161442-105161462GUAUUUCUCUCAAUUAUCCU1687
54790_1_3366+chr4: 105161462-105161482CGGCCUAAAUAGUAAAAGCU1688
54790_1_3367+chr4: 105161463-105161483GGCCUAAAUAGUAAAAGCUU1689
54790_1_3388+chr4: 105161583-105161603UUAAUAUUUUCCCUCUUUCU1690
54790_1_3396+chr4: 105161612-105161632GUUUCACAGUAAAUCAUAUA1691
54790_1_3403+chr4: 105161646-105161666AAGUGCUCAGAAUUUGAUUA1692
54790_1_3408+chr4: 105161673-105161693AAGUUAAUUUCUACUAAAAA1693
54790_1_3410+chr4: 105161674-105161694AGUUAAUUUCUACUAAAAAA1694
54790_1_3415+chr4: 105161697-105161717AUUCAAAUAGAACUUUCAUU1695
54790_1_3424+chr4: 105161721-105161741UGUACUGUAGUUUCACUUGA1696
54790_1_3425+chr4: 105161722-105161742GUACUGUAGUUUCACUUGAA1697
54790_1_3426+chr4: 105161723-105161743UACUGUAGUUUCACUUGAAG1698
54790_1_3430+chr4: 105161761-105161781CAUUGACUUAUUCAAUGCAU1699
54790_1_3440+chr4: 105161822-105161842UGUAUUAUAAAAUAUCAGAA1700
54790_1_3444+chr4: 105161848-105161868AUUGAAUCUGAUGCAUACCA1701
54790_1_3449+chr4: 105161858-105161878AUGCAUACCAAGGAGCAAUG1702
54790_1_3450+chr4: 105161868-105161888AGGAGCAAUGUGGAAAUUUU1703
54790_1_3460+chr4: 105161910-105161930UACUACUAAGUGUGUGUAUG1704
54790_1_3470+chr4: 105161957-105161977UAUUUAAGCUGAAUCCUCUU1705
54790_1_3475+chr4: 105161966-105161986UGAAUCCUCUUUGGUAGAAA1706
54790_1_3491+chr4: 105162068-105162088UUGAAAGUGCACAGAAUCCU1707
54790_1_3492+chr4: 105162069-105162089UGAAAGUGCACAGAAUCCUU1708
54790_1_3493+chr4: 105162070-105162090GAAAGUGCACAGAAUCCUUG1709
54790_1_3496+chr4: 105162097-105162117UUGUAUAAACUGUUUUUAUA1710
54790_1_3506+chr4: 105162119-105162139GUUCCUGUAGAAGACAGCUG1711
54790_1_3508+chr4: 105162155-105162175CACAAAACAAACAGCUUGCU1712
54790_1_3512+chr4: 105162177-105162197GUGAUGAUAACAUUCGUGCA1713
54790_1_3515+chr4: 105162178-105162198UGAUGAUAACAUUCGUGCAA1714
54790_1_3518+chr4: 105162196-105162216AAGGGAGUUCUCUCUUGCAU1715
54790_1_3520+chr4: 105162205-105162225CUCUCUUGCAUAGGAGUCCC1716
54790_1_3523+chr4: 105162229-105162249UACCCUAAUGCCUUCCCACA1717
54790_1_3527+chr4: 105162241-105162261UUCCCACAUGGUCAAACACA1718
54790_1_3539+chr4: 105162299-105162319AGCCUGCAGUUGUUUAUCAG1719
54790_1_3540+chr4: 105162300-105162320GCCUGCAGUUGUUUAUCAGU1720
54790_1_3542+chr4: 105162307-105162327GUUGUUUAUCAGUGGGAUAC1721
54790_1_3545+chr4: 105162308-105162328UUGUUUAUCAGUGGGAUACA1722
54790_1_3552+chr4: 105162319-105162339UGGGAUACAGGGAGAAAGAG1723
54790_1_3554+chr4: 105162350-105162370UUACUAACUGUUUAAUGACC1724
54790_1_3563+chr4: 105162385-105162405GAUACAGAAUAAGAAAGCAC1725
54790_1_3566+chr4: 105162397-105162417GAAAGCACUGGCCUGACUGC1726
54790_1_3568+chr4: 105162398-105162418AAAGCACUGGCCUGACUGCA1727
54790_1_3569+chr4: 105162399-105162419AAGCACUGGCCUGACUGCAG1728
54790_1_3571+chr4: 105162407-105162427GCCUGACUGCAGGGGAAACA1729
54790_1_3574+chr4: 105162421-105162441GAAACAUGGUAGAUGCCUAA1730
54790_1_3575+chr4: 105162424-105162444ACAUGGUAGAUGCCUAAAGG1731
54790_1_3587+chr4: 105162476-105162496AACUAUCAUUAUCACCUGAA1732
54790_1_3596+chr4: 105162530-105162550UUUAACCCUGACAAGCAAGU1733
54790_1_3602+chr4: 105162555-105162575CUUUAGUAUUCAAGAACUGA1734
54790_1_3608+chr4: 105162570-105162590ACUGAAGGUGACAAGCCCUG1735
54790_1_3622+chr4: 105162678-105162698CAUGCCUUCAUAGAAACAGU1736
54790_1_3659+chr4: 105162812-105162832GAACUAUUUUGCUUAACAUU1737
54790_1_3670+chr4: 105162847-105162867AGCCUAUAUCUGCAAUAAUA1738
54790_1_3672+chr4: 105162848-105162868GCCUAUAUCUGCAAUAAUAC1739
54790_1_3674+chr4: 105162849-105162869CCUAUAUCUGCAAUAAUACG1740
54790_1_3686+chr4: 105162898-105162918UAAUGAUAAAGAGAAAGAAA1741
54790_1_3691+chr4: 105162914-105162934GAAAAGGUGAGAAGUAAUUU1742
54790_1_3694+chr4: 105162915-105162935AAAAGGUGAGAAGUAAUUUU1743
54790_1_3698+chr4: 105162939-105162959AAUAUGCAAUGAUAAACUAG1744
54790_1_3704+chr4: 105162979-105162999ACCAGCAGCUGUGCUUAGCA1745
54790_1_3706+chr4: 105162995-105163015AGCAUGGAUAAUUGCCUAAA1746
54790_1_3713+chr4: 105163020-105163040GAGAAAAAAAAGUAAAAAUC1747
54790_1_3777+chr4: 105163278-105163298GCUUAUAAGACAUUGCCACC1748
54790_1_3789+chr4: 105163356-105163376UAUUUUCAAACAUAGAAUCA1749
54790_1_3797+chr4: 105163375-105163395AUGGAUUGCUACAAGCUGAA1750
54790_1_3807+chr4: 105163426-105163446UGCAUUUACAGAUGAGAAAA1751
54790_1_3810+chr4: 105163429-105163449AUUUACAGAUGAGAAAAUGG1752
54790_1_3814+chr4: 105163434-105163454CAGAUGAGAAAAUGGAGGCA1753
54790_1_3816+chr4: 105163435-105163455AGAUGAGAAAAUGGAGGCAU1754
54790_1_3822+chr4: 105163519-105163539UAUUGAUUAAGUUCUUAUGU1755
54790_1_3823+chr4: 105163520-105163540AUUGAUUAAGUUCUUAUGUU1756
54790_1_3834+chr4: 105163585-105163605UAUGUCAUCUAUAUUUUUGU1757
54790_1_3843+chr4: 105163613-105163633UUACUCUCCUCACUUUACUA1758
54790_1_3850+chr4: 105163630-105163650CUAAGGAAGAAACCAAGACA1759
54790_1_3852+chr4: 105163631-105163651UAAGGAAGAAACCAAGACAU1760
54790_1_3853+chr4: 105163632-105163652AAGGAAGAAACCAAGACAUG1761
54790_1_3857+chr4: 105163669-105163689UAUAAAUUUUGAAUUAUCUU1762
54790_1_3871+chr4: 105163743-105163763UAAAUCAACUCUUAAACAGU1763
54790_1_3873+chr4: 105163762-105163782UUGGAUGCCAACAAGCAGUC1764
54790_1_3876+chr4: 105163769-105163789CCAACAAGCAGUCUGGUGUU1765
54790_1_3908+chr4: 105163881-105163901UGUGUGUUCCAGCUUUGUUG1766
54790_1_3921+chr4: 105163977-105163997GUGAAGUGAUUAUUACUAUC1767
54790_1_3926+chr4: 105164023-105164043UCAGUCAUUUUUUGUGUUUA1768
54790_1_3939+chr4: 105164059-105164079GAGCUACUCAAAUGUAGUCA1769
54790_1_3943+chr4: 105164131-105164151GAAUGUAUUAAAUAUUCAUC1770
54790_1_3949+chr4: 105164189-105164209UUCCCCUACUACCCAGCCCA1771
54790_1_3963+chr4: 105164265-105164285UAUAAGUGAGAUCAUGCAAU1772
54790_1_3973+chr4: 105164323-105164343UAGCUGUGUAUGUCAUAUUC1773
54790_1_3985+chr4: 105164393-105164413AACUAAUAAUUCUUAUCUCA1774
54790_1_3989+chr4: 105164405-105164425UUAUCUCAUGGAUUACUGAG1775
54790_1_3994+chr4: 105164449-105164469AAAACAUCCAGCAUGUUACU1776
54790_1_4007+chr4: 105164517-105164537GUGUUGAGCAUCUAUGUAUC1777
54790_1_4013+chr4: 105164549-105164569AGCCAUCAUCUUUACCCUUC1778
54790_1_4015+chr4: 105164559-105164579UUUACCCUUCUGGAAUAUAC1779
54790_1_4019+chr4: 105164567-105164587UCUGGAAUAUACAGGCUCAU1780
54790_1_4033+chr4: 105164621-105164641CAUAAUGAGAUGAAAAUUAU1781
54790_1_4034+chr4: 105164634-105164654AAAUUAUAGGACUCAUAGAC1782
54790_1_4038+chr4: 105164644-105164664ACUCAUAGACUGGUCAGUUG1783
54790_1_4041+chr4: 105164655-105164675GGUCAGUUGAGGAAUUUCCC1784
54790_1_4045+chr4: 105164680-105164700GCUUCCAGCCUCUGCUCAAA1785
54790_1_4049+chr4: 105164706-105164726GAAUUCCCAGUUGCCUGAAU1786
54790_1_4052+chr4: 105164718-105164738GCCUGAAUAGGCGCCAGAGU1787
54790_1_4056+chr4: 105164738-105164758UGGCAUAGCUUUCUCAGUAU1788
54790_1_4057+chr4: 105164739-105164759GGCAUAGCUUUCUCAGUAUU1789
54790_1_4060+chr4: 105164749-105164769UCUCAGUAUUGGGACCUGAC1790
54790_1_4062+chr4: 105164750-105164770CUCAGUAUUGGGACCUGACA1791
54790_1_4069+chr4: 105164789-105164809ACAGCACAGCCUCUGAAGAU1792
54790_1_4072+chr4: 105164796-105164816AGCCUCUGAAGAUUGGCUCA1793
54790_1_4073+chr4: 105164797-105164817GCCUCUGAAGAUUGGCUCAA1794
54790_1_4076+chr4: 105164798-105164818CCUCUGAAGAUUGGCUCAAG1795
54790_1_4078+chr4: 105164799-105164819CUCUGAAGAUUGGCUCAAGG1796
54790_1_4082+chr4: 105164811-105164831GCUCAAGGGGGAAGAGAUGA1797
54790_1_4107+chr4: 105164955-105164975UAGAAAUAUUAAAUGAUAGC1798
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54790_1_4120+chr4: 105165024-105165044CUAUUUUGUAUCAUAUUUUC1800
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54790_1_4186+chr4: 105165283-105165303GAGAAUCACUUGAACCCAGG1823
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54790_1_4786+chr4: 105168115-105168135CCCCCUUCUUACCUCACCGU1887
54790_1_4794+chr4: 105168163-105168183GAUCAUUUAAAAAUUAAGUC1888
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54790_1_4826+chr4: 105168347-105168367CCUUGGUUUUCUUGCUGUCC1893
54790_1_4835+chr4: 105168377-105168397AAGAGCAUCCUUUUUCCUCC1894
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54790_1_4917+chr4: 105168651-105168671AGUGGUGAUUUGUGAGAUCU1907
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54790_1_4959+chr4: 105168909-105168929CAUUAAUUCAUUCCUUUUUA1910
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54790_1_4977+chr4: 105168979-105168999UCACCGAUUGACGAGCAUUU1912
54790_1_4978+chr4: 105168983-105169003CGAUUGACGAGCAUUUGGGU1913
54790_1_4995+chr4: 105169066-105169086AUAUAAUGACUUUUUUCCUC1914
54790_1_4996+chr4: 105169067-105169087UAUAAUGACUUUUUUCCUCU1915
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54790_1_5005+chr4: 105169085-105169105CUGGGUAGAUACCCAGUAGU1917
54790_1_5007+chr4: 105169093-105169113AUACCCAGUAGUGGGAUUGC1918
54790_1_5008+chr4: 105169102-105169122AGUGGGAUUGCUGGAUCAAA1919
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54790_1_5020+chr4: 105169153-105169173CUCCACACUGUUUUCCAUAG1921
54790_1_5036+chr4: 105169257-105169277UUUUUUAUUGCCGUUCUUGC1922
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54790_1_5059+chr4: 105169337-105169357ACAUUUUCUCAUAUGUUUGU1924
54790_1_5076+chr4: 105169398-105169418UCCUUAGCCCACUUUUUGAU1925
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54790_1_5247+chr4: 105170036-105170056UAGUUUUGCUUUGGCUCUGU1952
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54790_1_5309+chr4: 105170212-105170232GAUGUGAGUUCUAUGAGAUG1958
54790_1_5312+chr4: 105170224-105170244AUGAGAUGAGGAACAUUGUU1959
54790_1_5313+chr4: 105170225-105170245UGAGAUGAGGAACAUUGUUU1960
54790_1_5317+chr4: 105170260-105170280AUUGUCAGCAUACCAAACAG1961
54790_1_5319+chr4: 105170271-105170291ACCAAACAGUGGCUAGCACA1962
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54790_1_5342+chr4: 105170397-105170417UUGCCUGAGUCUCAAAAGUU1969
54790_1_5343+chr4: 105170398-105170418UGCCUGAGUCUCAAAAGUUU1970
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54790_1_5646+chr4: 105171905-105171925AUAGCAUGCAUUUCUCAGAC2014
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54790_1_5661+chr4: 105171983-105172003UAUAUCCUUGGUUUUUCAUG2019
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54790_1_9610−chr4: 105147081-105147101CUCUUCCCUCUUGGUAUUUG2762
54790_1_9614−chr4: 105147090-105147110GAAGCUUCCCUCUUCCCUCU2763
54790_1_9619−chr4: 105147127-105147147AUUUGUCAGCCAUGUUGAAG2764
54790_1_9625−chr4: 105147162-105147182ACAGGUUUAAAAGGGGUAGA2765
54790_1_9627−chr4: 105147163-105147183UACAGGUUUAAAAGGGGUAG2766
54790_1_9631−chr4: 105147169-105147189CAGAACUACAGGUUUAAAAG2767
54790_1_9632−chr4: 105147170-105147190ACAGAACUACAGGUUUAAAA2768
54790_1_9634−chr4: 105147171-105147191CACAGAACUACAGGUUUAAA2769
54790_1_9636−chr4: 105147180-105147200AGAAGAGAACACAGAACUAC2770
54790_1_9647−chr4: 105147205-105147225AUGAGGGGACGAGCAUUAGG2771
54790_1_9649−chr4: 105147208-105147228GAGAUGAGGGGACGAGCAUU2772
54790_1_9656−chr4: 105147220-105147240UAAGUUUUCUGGGAGAUGAG2773
54790_1_9658−chr4: 105147221-105147241GUAAGUUUUCUGGGAGAUGA2774
54790_1_9660−chr4: 105147222-105147242GGUAAGUUUUCUGGGAGAUG2775
54790_1_9663−chr4: 105147230-105147250GGCACAAAGGUAAGUUUUCU2776
54790_1_9666−chr4: 105147231-105147251AGGCACAAAGGUAAGUUUUC2777
54790_1_9668−chr4: 105147243-105147263CCGGCUCGUCGGAGGCACAA2778
54790_1_9669−chr4: 105147251-105147271CCGGGAAACCGGCUCGUCGG2779
54790_1_9671−chr4: 105147254-105147274AGGCCGGGAAACCGGCUCGU2780
54790_1_9674−chr4: 105147262-105147282AUUAAAAAAGGCCGGGAAAC2781
54790_1_9678−chr4: 105147269-105147289UCUGAGGAUUAAAAAAGGCC2782
54790_1_9681−chr4: 105147270-105147290UUCUGAGGAUUAAAAAAGGC2783
54790_1_9683−chr4: 105147274-105147294ACUUUUCUGAGGAUUAAAAA2784
54790_1_9686−chr4: 105147285-105147305AUUUAAAAAUCACUUUUCUG2785
54790_1_9692−chr4: 105147315-105147335AAAGCUGAACUAUUUUAGAA2786
54790_1_9699−chr4: 105147353-105147373AACAGGGGAAGAGGAUUAAA2787
54790_1_9701−chr4: 105147354-105147374AAACAGGGGAAGAGGAUUAA2788
54790_1_9704−chr4: 105147362-105147382CACGAAAGAAACAGGGGAAG2789
54790_1_9710−chr4: 105147368-105147388CACUUACACGAAAGAAACAG2790
54790_1_9712−chr4: 105147369-105147389UCACUUACACGAAAGAAACA2791
54790_1_9713−chr4: 105147370-105147390UUCACUUACACGAAAGAAAC2792
54790_1_9721−chr4: 105147401-105147421UGAGGUUGUUCAGGAUAAAC2793
54790_1_9723−chr4: 105147402-105147422CUGAGGUUGUUCAGGAUAAA2794
54790_1_9726−chr4: 105147410-105147430UGUUCUCUCUGAGGUUGUUC2795
54790_1_9728−chr4: 105147419-105147439CCCUAUCAGUGUUCUCUCUG2796
54790_1_9731−chr4: 105147452-105147472AGACCCUACAGCUGAUAAAA2797
54790_1_9732−chr4: 105147453-105147473CAGACCCUACAGCUGAUAAA2798
54790_1_9734−chr4: 105147494-105147514GGGGAUAAGAAGGUAGGAGG2799
54790_1_9736−chr4: 105147497-105147517AAGGGGGAUAAGAAGGUAGG2800
54790_1_9738−chr4: 105147500-105147520CUAAAGGGGGAUAAGAAGGU2801
54790_1_9741−chr4: 105147504-105147524CCCCCUAAAGGGGGAUAAGA2802
54790_1_9746−chr4: 105147513-105147533UUCGUACAGCCCCCUAAAGG2803
54790_1_9748−chr4: 105147514-105147534CUUCGUACAGCCCCCUAAAG2804
54790_1_9749−chr4: 105147515-105147535ACUUCGUACAGCCCCCUAAA2805
54790_1_9752−chr4: 105147516-105147536CACUUCGUACAGCCCCCUAA2806
54790_1_9757−chr4: 105147587-105147607UAACAAAACGCGCGGACUUA2807
54790_1_9759−chr4: 105147595-105147615AGCGCCGCUAACAAAACGCG2808
54790_1_9773−chr4: 105147650-105147670GUGAGUUCUGGUCUUGUUUG2809
54790_1_9775−chr4: 105147651-105147671AGUGAGUUCUGGUCUUGUUU2810
54790_1_9777−chr4: 105147652-105147672AAGUGAGUUCUGGUCUUGUU2811
54790_1_9781−chr4: 105147662-105147682ACCUUGAGAAAAGUGAGUUC2812
54790_1_9787−chr4: 105147708-105147728CAUACAUUCCCCAGGCUGGA2813
54790_1_9789−chr4: 105147712-105147732CUUACAUACAUUCCCCAGGC2814
54790_1_9792−chr4: 105147716-105147736UUCUCUUACAUACAUUCCCC2815
54790_1_9796−chr4: 105147758-105147778UUCGGGAGAAGCACAAAGCC2816
54790_1_9798−chr4: 105147759-105147779AUUCGGGAGAAGCACAAAGC2817
54790_1_9802−chr4: 105147775-105147795GAACCAAACGAAGCUGAUUC2818
54790_1_9805−chr4: 105147776-105147796GGAACCAAACGAAGCUGAUU2819
54790_1_9811−chr4: 105147797-105147817UGUCUGCCUGUCACUUACCA2820
54790_1_9814−chr4: 105147836-105147856CCCCCUCCCGCCCCCUCCCC2821
54790_1_9815−chr4: 105147837-105147857ACCCCCUCCCGCCCCCUCCC2822
54790_1_9827−chr4: 105147904-105147924GGAUUGGGUUUCAUUUCUUU2823
54790_1_9831−chr4: 105147919-105147939UUCACUUCUUUGCUGGGAUU2824
54790_1_9832−chr4: 105147920-105147940CUUCACUUCUUUGCUGGGAU2825
54790_1_9834−chr4: 105147925-105147945CUGCUCUUCACUUCUUUGCU2826
54790_1_9836−chr4: 105147926-105147946UCUGCUCUUCACUUCUUUGC2827
54790_1_9841−chr4: 105147960-105147980UCGGUUUCUCUAAUUUGGAU2828
54790_1_9842−chr4: 105147961-105147981UUCGGUUUCUCUAAUUUGGA2829
54790_1_9845−chr4: 105147965-105147985UCUCUUCGGUUUCUCUAAUU2830
54790_1_9856−chr4: 105148009-105148029CUCUCCUCUGUGUCUCUCUU2831
54790_1_9860−chr4: 105148026-105148046UCUCUCUUCUUUCUCAUCUC2832
54790_1_9875−chr4: 105148085-105148105GAUUCAGCAAGAUGCGAGUG2833
54790_1_9884−chr4: 105148171-105148191GCCACACUUCAUUAUGUCAU2834
54790_1_9889−chr4: 105148193-105148213GCCUUUCCAGGAGUCUAUCC2835
54790_1_9894−chr4: 105148205-105148225AUUUCAUUUUCGGCCUUUCC2836
54790_1_9897−chr4: 105148215-105148235UAACACUUAUAUUUCAUUUU2837
54790_1_9900−chr4: 105148251-105148271AAUUAAAAGUAUAUCAUGAG2838
54790_1_9901−chr4: 105148252-105148272UAAUUAAAAGUAUAUCAUGA2839
54790_1_9904−chr4: 105148253-105148273GUAAUUAAAAGUAUAUCAUG2840
54790_1_9912−chr4: 105148290-105148310CUUAAACAUUAGAUGAAGAA2841
54790_1_9914−chr4: 105148291-105148311UCUUAAACAUUAGAUGAAGA2842
54790_1_9929−chr4: 105148334-105148354UAUGCACUAAAUUUUACCGC2843
54790_1_9945−chr4: 105148446-105148466AUUAUAAUCCCUGACUGAAG2844
54790_1_9946−chr4: 105148447-105148467CAUUAUAAUCCCUGACUGAA2845
54790_1_9949−chr4: 105148448-105148468CCAUUAUAAUCCCUGACUGA2846
54790_1_9959−chr4: 105148475-105148495UGAUGAAUAUCUUUGAAUUU2847
54790_1_9960−chr4: 105148476-105148496UUGAUGAAUAUCUUUGAAUU2848
54790_1_9967−chr4: 105148507-105148527AUACAAUCUUAUUCCUAUGA2849
54790_1_9977−chr4: 105148600-105148620AUGUAAUGAUUUCAUUAGCC2850
54790_1_10028−chr4: 105148861-105148881AGUUUUGGAAAUUCGACUUA2851
54790_1_10032−chr4: 105148876-105148896CUAUCGAGGACAAAUAGUUU2852
54790_1_10035−chr4: 105148890-105148910AGUUACAAAGUGAACUAUCG2853
54790_1_10066−chr4: 105149048-105149068UAAUUUUUGUUUUAAUUUUA2854
54790_1_10067−chr4: 105149049-105149069CUAAUUUUUGUUUUAAUUUU2855
54790_1_10072−chr4: 105149079-105149099UUUACCAUGAACAGCAUUAA2856
54790_1_10086−chr4: 105149129-105149149UGUUUUUAAUUCUGAAUUGC2857
54790_1_10094−chr4: 105149155-105149175AAUAUUAGUUUGUUAGCAAA2858
54790_1_10113−chr4: 105149258-105149278AGUUAUUCUUAUUUAUUGAG2859
54790_1_10123−chr4: 105149326-105149346AAGAAUCUAAAUUUGAUGAC2860
54790_1_10131−chr4: 105149363-105149383GCUAUUUUCAGUAUAAAAGU2861
54790_1_10145−chr4: 105149454-105149474UAAUUUCUCUUUUCCAACAA2862
54790_1_10153−chr4: 105149516-105149536AUAUGGUAAAGAAAGAACUG2863
54790_1_10158−chr4: 105149533-105149553AGGUAGUAUGAUCACAUAUA2864
54790_1_10163−chr4: 105149553-105149573AUGGAAUUUUUGGAGCACCU2865
54790_1_10165−chr4: 105149563-105149583AGACAGUCCUAUGGAAUUUU2866
54790_1_10169−chr4: 105149572-105149592AAUAACCCAAGACAGUCCUA2867
54790_1_10189−chr4: 105149719-105149739UGACAAUUUAAACAAAGCAA2868
54790_1_10191−chr4: 105149720-105149740AUGACAAUUUAAACAAAGCA2869
54790_1_10197−chr4: 105149748-105149768UUAAAGCCUUAAGAAGAGUU2870
54790_1_10203−chr4: 105149785-105149805CUCCGGCUUCUGGCAUAAAC2871
54790_1_10204−chr4: 105149795-105149815AUAUCAAUUCCUCCGGCUUC2872
54790_1_10205−chr4: 105149802-105149822CAAAAUCAUAUCAAUUCCUC2873
54790_1_10208−chr4: 105149842-105149862UUCACUUGCCAAUGUCUAGU2874
54790_1_10215−chr4: 105149873-105149893CAGGUGCACUUCACUUGUUC2875
54790_1_10220−chr4: 105149892-105149912UUUCAUAACAACUCCUUGGC2876
54790_1_10223−chr4: 105149896-105149916AUUCUUUCAUAACAACUCCU2877
54790_1_10224−chr4: 105149920-105149940CCAGUGCCCAAUAAGGACUU2878
54790_1_10227−chr4: 105149927-105149947UACAAGACCAGUGCCCAAUA2879
54790_1_10241−chr4: 105150006-105150026GAGUCUUAGAAGAAUUGAUA2880
54790_1_10242−chr4: 105150007-105150027GGAGUCUUAGAAGAAUUGAU2881
54790_1_10255−chr4: 105150028-105150048CUUACAACAUUGUUUGGGGG2882
54790_1_10257−chr4: 105150031-105150051UGACUUACAACAUUGUUUGG2883
54790_1_10258−chr4: 105150032-105150052UUGACUUACAACAUUGUUUG2884
54790_1_10260−chr4: 105150033-105150053UUUGACUUACAACAUUGUUU2885
54790_1_10262−chr4: 105150034-105150054AUUUGACUUACAACAUUGUU2886
54790_1_10270−chr4: 105150077-105150097CUUAAUGAGGUCAGUAAUUA2887
54790_1_10272−chr4: 105150090-105150110AUAAGAAGGGCUUCUUAAUG2888
54790_1_10274−chr4: 105150103-105150123GUGCCUAUGAAUCAUAAGAA2889
54790_1_10275−chr4: 105150104-105150124UGUGCCUAUGAAUCAUAAGA2890
54790_1_10282−chr4: 105150127-105150147UGGAAAAUAGAGUUUCUGUG2891
54790_1_10288−chr4: 105150147-105150167UACUCAGACUUUGGGCAGGA2892
54790_1_10292−chr4: 105150151-105150171UACCUACUCAGACUUUGGGC2893
54790_1_10294−chr4: 105150155-105150175AAUUUACCUACUCAGACUUU2894
54790_1_10295−chr4: 105150156-105150176GAAUUUACCUACUCAGACUU2895
54790_1_10310−chr4: 105150200-105150220UUUGAAGAUAUUUUAUUUCA2896
54790_1_10339−chr4: 105150421-105150441UAACAUUAAAACAGUCUACA2897
54790_1_10344−chr4: 105150450-105150470UUUUAGCCUGUUCCCAAGGU2898
54790_1_10347−chr4: 105150454-105150474AAAGUUUUAGCCUGUUCCCA2899
54790_1_10349−chr4: 105150480-105150500GAUGAACAAAUACUGACAGC2900
54790_1_10355−chr4: 105150532-105150552CCUUAAGAACUACUGUGCAA2901
54790_1_10363−chr4: 105150567-105150587UAUUCUAUUGCUGCUGGCUU2902
54790_1_10365−chr4: 105150573-105150593GGGAGAUAUUCUAUUGCUGC2903
54790_1_10368−chr4: 105150593-105150613UCCAAUUGUAAAGUUGGCUU2904
54790_1_10371−chr4: 105150594-105150614CUCCAAUUGUAAAGUUGGCU2905
54790_1_10373−chr4: 105150599-105150619GAAGGCUCCAAUUGUAAAGU2906
54790_1_10377−chr4: 105150617-105150637ACUGGUCUUUCCCACAGUGA2907
54790_1_10379−chr4: 105150635-105150655CACCAGCUCUACUUGGCAAC2908
54790_1_10382−chr4: 105150642-105150662AGAUAACCACCAGCUCUACU2909
54790_1_10390−chr4: 105150689-105150709AUAUUUGGCAAAAUCAUUUG2910
54790_1_10391−chr4: 105150704-105150724CCAAGUAAAUACUGUAUAUU2911
54790_1_10397−chr4: 105150736-105150756CAGUGAGUAGAAAUAGAAAU2912
54790_1_10403−chr4: 105150759-105150779UCACAGUAUUCACUCAGUUU2913
54790_1_10411−chr4: 105150844-105150864UGACUUUCCCCUUUCCCUCC2914
54790_1_10420−chr4: 105150894-105150914CAGACAUACAUAAUUCUUUU2915
54790_1_10422−chr4: 105150923-105150943AUAUAGGACAAAAAUAAUGC2916
54790_1_10425−chr4: 105150939-105150959GUCUCUGCAAUGUACAAUAU2917
54790_1_10442−chr4: 105151019-105151039CCAAAAUUUGUUAUUUGGAA2918
54790_1_10444−chr4: 105151024-105151044GGGAUCCAAAAUUUGUUAUU2919
54790_1_10449−chr4: 105151061-105151081AGGGUUUCACGAUCCUAAUG2920
54790_1_10451−chr4: 105151069-105151089GGAACCGGAGGGUUUCACGA2921
54790_1_10453−chr4: 105151086-105151106GGAGUUCACUAGAGAGUGGA2922
54790_1_10457−chr4: 105151109-105151129GGUCCCACCAAAGUUUGAGG2923
54790_1_10458−chr4: 105151123-105151143GGACUGACACAACGGGUCCC2924
54790_1_10459−chr4: 105151126-105151146CCCGGACUGACACAACGGGU2925
54790_1_10460−chr4: 105151127-105151147CCCCGGACUGACACAACGGG2926
54790_1_10471−chr4: 105151146-105151166AUUUAAAAAACAUCUCUGAC2927
54790_1_10472−chr4: 105151147-105151167AAUUUAAAAAACAUCUCUGA2928
54790_1_10474−chr4: 105151148-105151168AAAUUUAAAAAACAUCUCUG2929
54790_1_10477−chr4: 105151197-105151217AGGACUCAUCGACCCUGAUG2930
54790_1_10480−chr4: 105151205-105151225AGAGUCAGAGGACUCAUCGA2931
54790_1_10482−chr4: 105151206-105151226UAGAGUCAGAGGACUCAUCG2932
54790_1_10492−chr4: 105151281-105151301AACGGACCCGACCUCGCGUC2933
54790_1_10494−chr4: 105151291-105151311AGAGAGGGAGAACGGACCCG2934
54790_1_10496−chr4: 105151295-105151315UCCCAGAGAGGGAGAACGGA2935
54790_1_10498−chr4: 105151296-105151316AUCCCAGAGAGGGAGAACGG2936
54790_1_10505−chr4: 105151314-105151334ACAACACGCUGAAACUCUAU2937
54790_1_10507−chr4: 105151315-105151335AACAACACGCUGAAACUCUA2938
54790_1_10519−chr4: 105151343-105151363AAUGUGCUUAAAACAAACAA2939
54790_1_10552−chr4: 105151541-105151561GAAUUCUUAAAACUGCAGGU2940
54790_1_10554−chr4: 105151545-105151565UUCUGAAUUCUUAAAACUGC2941
54790_1_10557−chr4: 105151574-105151594GGUCUUACUCGGUGGUGUGG2942
54790_1_10563−chr4: 105151625-105151645GGUCCGACCAGAUCUUGAAG2943
54790_1_10566−chr4: 105151639-105151659AGAGUGAUACAACGGGUCCG2944
54790_1_10567−chr4: 105151643-105151663CCAUAGAGUGAUACAACGGG2945
54790_1_10577−chr4: 105151664-105151684AUAAAAAUAACUUAUCUCUG2946
54790_1_10597−chr4: 105151737-105151757AUGAUUUCAAGUCAGUUUAG2947
54790_1_10609−chr4: 105151763-105151783ACUUUAAUUCUCAGUUUAUU2948
54790_1_10612−chr4: 105151797-105151817GUCCGUACUCGGUGGUGUUG2949
54790_1_10614−chr4: 105151816-105151836AGGGUUUCACGACCCUAAUG2950
54790_1_10616−chr4: 105151824-105151844GGAACAGCAGGGUUUCACGA2951
54790_1_10617−chr4: 105151825-105151845CGGAACAGCAGGGUUUCACG2952
54790_1_10620−chr4: 105151858-105151878CCAGAGUUUGAGGACUGGAG2953
54790_1_10624−chr4: 105151879-105151899AAAGUGGUACAACCGGUCCG2954
54790_1_10625−chr4: 105151883-105151903UCCCAAAGUGGUACAACCGG2955
54790_1_10626−chr4: 105151888-105151908CUCUGUCCCAAAGUGGUACA2956
54790_1_10635−chr4: 105151902-105151922AACAUAAAAAUCAUCUCUGU2957
54790_1_10636−chr4: 105151903-105151923AAACAUAAAAAUCAUCUCUG2958
54790_1_10640−chr4: 105151932-105151952GACCACACACGGUGGUACGG2959
54790_1_10641−chr4: 105151951-105151971AGGACUCAUCGACCCUAAUG2960
54790_1_10642−chr4: 105151959-105151979GGAGUCGGAGGACUCAUCGA2961
54790_1_10643−chr4: 105151960-105151980CGGAGUCGGAGGACUCAUCG2962
54790_1_10648−chr4: 105151982-105152002GGGUCCGAGUUCACUAAGAG2963
54790_1_10649−chr4: 105151983-105152003CGGGUCCGAGUUCACUAAGA2964
54790_1_10652−chr4: 105151999-105152019UCCAUACUCGGUGGUACGGG2965
54790_1_10654−chr4: 105152019-105152039AGGGUUUCACGACCCUAAUA2966
54790_1_10655−chr4: 105152027-105152047GGAGCCGGAGGGUUUCACGA2967
54790_1_10657−chr4: 105152028-105152048CGGAGCCGGAGGGUUUCACG2968
54790_1_10659−chr4: 105152044-105152064CAGUCCACUAGGUGGACGGA2969
54790_1_10661−chr4: 105152061-105152081CCAGAGCUUAAGGACUGCAG2970
54790_1_10666−chr4: 105152082-105152102AAAGUGGUACAACCGGUCUG2971
54790_1_10667−chr4: 105152091-105152111CUCUACCCCAAAGUGGUACA2972
54790_1_10673−chr4: 105152105-105152125AACAUACAAAUCACCUCUAC2973
54790_1_10674−chr4: 105152106-105152126AAACAUACAAAUCACCUCUA2974
54790_1_10676−chr4: 105152107-105152127AAAACAUACAAAUCACCUCU2975
54790_1_10678−chr4: 105152113-105152133UCGAUUAAAACAUACAAAUC2976
54790_1_10681−chr4: 105152153-105152173AGGUCUUAUCGACUCUGAUG2977
54790_1_10686−chr4: 105152201-105152221CGUCGGAGACGGAGGGCCCU2978
54790_1_10687−chr4: 105152202-105152222GCGUCGGAGACGGAGGGCCC2979
54790_1_10690−chr4: 105152205-105152225GUGGCGUCGGAGACGGAGGG2980
54790_1_10691−chr4: 105152206-105152226AGUGGCGUCGGAGACGGAGG2981
54790_1_10694−chr4: 105152230-105152250CCUCACGUCGUCUCGGUAGA2982
54790_1_10696−chr4: 105152251-105152271AGAGAGACGGAGCGGGUCCG2983
54790_1_10699−chr4: 105152255-105152275UCUCAGAGAGACGGAGCGGG2984
54790_1_10714−chr4: 105152279-105152299UUAUUAAAAAAGAAAAAAAC2985
54790_1_10745−chr4: 105152466-105152486GUCAACAGUAGGUUCUAUUA2986
54790_1_10746−chr4: 105152467-105152487GGUCAACAGUAGGUUCUAUU2987
54790_1_10750−chr4: 105152477-105152497UUGACUGAGAGGUCAACAGU2988
54790_1_10752−chr4: 105152488-105152508UCCAUUAAAUAUUGACUGAG2989
54790_1_10770−chr4: 105152532-105152552UUUUUUCUAGUUAAAUUGCA2990
54790_1_10774−chr4: 105152577-105152597UUUCUUUCUUUGAAAGAAAA2991
54790_1_10782−chr4: 105152640-105152660UGUGGUGACGUGAGGUCGGA2992
54790_1_10787−chr4: 105152681-105152701GUGAACUUGGACCUUCCGUC2993
54790_1_10789−chr4: 105152687-105152707CUCUUAGUGAACUUGGACCU2994
54790_1_10790−chr4: 105152691-105152711CUUUCUCUUAGUGAACUUGG2995
54790_1_10798−chr4: 105152718-105152738GGAUCAGGGUCGAUGAGACC2996
54790_1_10799−chr4: 105152719-105152739AGGAUCAGGGUCGAUGAGAC2997
54790_1_10801−chr4: 105152720-105152740GAGGAUCAGGGUCGAUGAGA2998
54790_1_10803−chr4: 105152721-105152741CGAGGAUCAGGGUCGAUGAG2999
54790_1_10806−chr4: 105152747-105152767UUUUAAUCGGUCCACACCAC3000
54790_1_10807−chr4: 105152748-105152768UUUUUAAUCGGUCCACACCA3001
54790_1_10808−chr4: 105152749-105152769CUUUUUAAUCGGUCCACACC3002
54790_1_10811−chr4: 105152752-105152772UAUCUUUUUAAUCGGUCCAC3003
54790_1_10812−chr4: 105152757-105152777AUUUUUAUCUUUUUAAUCGG3004
54790_1_10815−chr4: 105152797-105152817GCUCUAGUCGGACCGGUUGU3005
54790_1_10816−chr4: 105152806-105152826GGUCCUCAUGCUCUAGUCGG3006
54790_1_10818−chr4: 105152824-105152844GUCCGUCUAGUGGACUCUGG3007
54790_1_10824−chr4: 105152843-105152863CGUGAAACCCUCUGGGCCCG3008
54790_1_10825−chr4: 105152847-105152867GGGUCGUGAAACCCUCUGGG3009
54790_1_10826−chr4: 105152848-105152868AGGGUCGUGAAACCCUCUGG3010
54790_1_10828−chr4: 105152856-105152876CGGACAUUAGGGUCGUGAAA3011
54790_1_10831−chr4: 105152857-105152877ACGGACAUUAGGGUCGUGAA3012
54790_1_10834−chr4: 105152884-105152904AUAGAUUACUGGUCCACGUC3013
54790_1_10837−chr4: 105152892-105152912CAUUGAAAAUAGAUUACUGG3014
54790_1_10847−chr4: 105152981-105153001GCCUGUAGAAAUUAAAUGUA3015
54790_1_10855−chr4: 105153015-105153035UAAAAUGGGUGGCUUUUAUA3016
54790_1_10857−chr4: 105153016-105153036UUAAAAUGGGUGGCUUUUAU3017
54790_1_10862−chr4: 105153026-105153046ACUUUUGUGCUUAAAAUGGG3018
54790_1_10863−chr4: 105153029-105153049UUCACUUUUGUGCUUAAAAU3019
54790_1_10864−chr4: 105153030-105153050AUUCACUUUUGUGCUUAAAA3020
54790_1_10876−chr4: 105153127-105153147GAGACAUAAUAAAGUAUGUU3021
54790_1_10878−chr4: 105153155-105153175CCUUUAACUCGUUCAUAUGC3022
54790_1_10887−chr4: 105153176-105153196AACGUUUCACAACGGUGACC3023
54790_1_10889−chr4: 105153177-105153197AAACGUUUCACAACGGUGAC3024
54790_1_10892−chr4: 105153178-105153198AAAACGUUUCACAACGGUGA3025
54790_1_10894−chr4: 105153179-105153199CAAAACGUUUCACAACGGUG3026
54790_1_10901−chr4: 105153250-105153270GGUGUAGUUACAGUCAUAGU3027
54790_1_10903−chr4: 105153273-105153293CUGUAGACUUAUUCUAAUCA3028
54790_1_10906−chr4: 105153295-105153315UUACUCAUGUUCAAUUUGAC3029
54790_1_10910−chr4: 105153338-105153358UAUGUGAUGUACACUGAUUU3030
54790_1_10917−chr4: 105153369-105153389UUCUCUGUUUUGAGAAAAAA3031
54790_1_10930−chr4: 105153443-105153463UUCUGACACACAUUUUAAUA3032
54790_1_10936−chr4: 105153491-105153511AAGGCCAUUCUAUCAAAAAA3033
54790_1_10943−chr4: 105153510-105153530UUAAAAUAUUUUUAACAUAA3034
54790_1_10949−chr4: 105153580-105153600UUCUUAUUAUGGAUAGAGAU3035
54790_1_10950−chr4: 105153581-105153601AUUCUUAUUAUGGAUAGAGA3036
54790_1_10956−chr4: 105153605-105153625UCAAAGGAGUGAGUAUUUAU3037
54790_1_10958−chr4: 105153606-105153626GUCAAAGGAGUGAGUAUUUA3038
54790_1_10964−chr4: 105153632-105153652CCUUCAAUAAAUUGGAGUGA3039
54790_1_10965−chr4: 105153633-105153653UCCUUCAAUAAAUUGGAGUG3040
54790_1_10968−chr4: 105153653-105153673CAUAUCCGACAUACUUGAAU3041
54790_1_10971−chr4: 105153669-105153689CGAUUCGGAUUCGGUACAUA3042
54790_1_10973−chr4: 105153691-105153711UCUGACGAAUUGAGUUUACG3043
54790_1_10978−chr4: 105153724-105153744UUAUAUCACUAAUUUUCUAA3044
54790_1_11000−chr4: 105153858-105153878UAUUACGACAUUACUUGUAA3045
54790_1_11011−chr4: 105153906-105153926AGUACUGUACUAUCUGUAGA3046
54790_1_11012−chr4: 105153907-105153927GAGUACUGUACUAUCUGUAG3047
54790_1_11021−chr4: 105153953-105153973GAAUUAUUAUAAAGUGACAU3048
54790_1_11034−chr4: 105154042-105154062UUAACUUUCGUAUAGUAUAC3049
54790_1_11041−chr4: 105154076-105154096GAGGAAUCUAAACGGAUAAG3050
54790_1_11047−chr4: 105154151-105154171UUUCUUUAGAGUAUGAAUAA3051
54790_1_11062−chr4: 105154216-105154236AAGUCGUAUAAGUUUCUCAA3052
54790_1_11063−chr4: 105154217-105154237AAAGUCGUAUAAGUUUCUCA3053
54790_1_11070−chr4: 105154240-105154260AAAUUUCGUAUAUUAAGUCA3054
54790_1_11071−chr4: 105154241-105154261AAAAUUUCGUAUAUUAAGUC3055
54790_1_11102−chr4: 105154455-105154475AGGGUUUCACGGUCCUAAUG3056
54790_1_11103−chr4: 105154463-105154483GGAACCGGAGGGUUUCACGG3057
54790_1_11106−chr4: 105154480-105154500UUUGAAGACCAGAGGGCGGA3058
54790_1_11108−chr4: 105154493-105154513GGUCUGAUUAGAGUUUGAAG3059
54790_1_11111−chr4: 105154523-105154543GUAUCCUUCUCAUCUAUAAG3060
54790_1_11122−chr4: 105154589-105154609UCUUCCCAUAUGAGCUCUAA3061
54790_1_11134−chr4: 105154697-105154717AUCUCCUGAACUGAAUGGCU3062
54790_1_11136−chr4: 105154702-105154722GUUACAUCUCCUGAACUGAA3063
54790_1_11143−chr4: 105154724-105154744AGACAUUCCUUUUAACACUU3064
54790_1_11144−chr4: 105154725-105154745CAGACAUUCCUUUUAACACU3065
54790_1_11148−chr4: 105154766-105154786AGCGUUUCACGACCCUAAUG3066
54790_1_11150−chr4: 105154774-105154794GAAGGCGGAGCGUUUCACGA3067
54790_1_11152−chr4: 105154775-105154795UGAAGGCGGAGCGUUUCACG3068
54790_1_11161−chr4: 105154833-105154853CCCCAAAACGGUACAACGGG3069
54790_1_11169−chr4: 105154852-105154872CACGUAAAAAACAUCCCUAC3070
54790_1_11170−chr4: 105154853-105154873ACACGUAAAAAACAUCCCUA3071
54790_1_11172−chr4: 105154854-105154874AACACGUAAAAAACAUCCCU3072
54790_1_11174−chr4: 105154858-105154878AUUAAACACGUAAAAAACAU3073
54790_1_11176−chr4: 105154859-105154879GAUUAAACACGUAAAAAACA3074
54790_1_11178−chr4: 105154900-105154920GUGUUCAUGGACCUUGAUGU3075
54790_1_11180−chr4: 105154901-105154921GGUGUUCAUGGACCUUGAUG3076
54790_1_11182−chr4: 105154910-105154930CGGAGUCGGGGUGUUCAUGG3077
54790_1_11187−chr4: 105154949-105154969GUGACGUCGGAGUUGAAGGG3078
54790_1_11188−chr4: 105154974-105154994CUUCACACCCCCGUGGUUGU3079
54790_1_11192−chr4: 105154985-105155005AGUGGGUCCGACUUCACACC3080
54790_1_11193−chr4: 105154986-105155006CAGUGGGUCCGACUUCACAC3081
54790_1_11195−chr4: 105154987-105155007ACAGUGGGUCCGACUUCACA3082
54790_1_11197−chr4: 105154988-105155008AACAGUGGGUCCGACUUCAC3083
54790_1_11200−chr4: 105154999-105155019UCCCAGAGUAAAACAGUGGG3084
54790_1_11212−chr4: 105155018-105155038UAGAAAAAAAAACUCUCUCU3085
54790_1_11214−chr4: 105155019-105155039AUAGAAAAAAAAACUCUCUC3086
54790_1_11250−chr4: 105155211-105155231AAAAUCUGAAACAUGACAAG3087
54790_1_11264−chr4: 105155284-105155304AUGCCACAGUAUCAGUUAAC3088
54790_1_11284−chr4: 105155364-105155384CCCUGUUUCUCACUUUGUCC3089
54790_1_11288−chr4: 105155406-105155426GCAGCCAUGUGUAGCAAAGA3090
54790_1_11295−chr4: 105155444-105155464GUGGUUUGUAGAAGUUCUGC3091
54790_1_11301−chr4: 105155463-105155483GCACUCAUUUUACCUGUAAG3092
54790_1_11304−chr4: 105155503-105155523CUACAAGUCAUAGUUCCAUA3093
54790_1_11305−chr4: 105155504-105155524ACUACAAGUCAUAGUUCCAU3094
54790_1_11313−chr4: 105155578-105155598CUGGUAUCUAGAAUUACAUA3095
54790_1_11316−chr4: 105155597-105155617CAUUGCACAACAAGAAUGUC3096
54790_1_11322−chr4: 105155627-105155647CAUUCUCAUGAGAAUAAAAA3097
54790_1_11324−chr4: 105155628-105155648GCAUUCUCAUGAGAAUAAAA3098
54790_1_11329−chr4: 105155661-105155681CCCAAGGUAUGGGAUCCAAC3099
54790_1_11331−chr4: 105155671-105155691CAGUCAUGGUCCCAAGGUAU3100
54790_1_11332−chr4: 105155672-105155692UCAGUCAUGGUCCCAAGGUA3101
54790_1_11335−chr4: 105155677-105155697AGUUAUCAGUCAUGGUCCCA3102
54790_1_11339−chr4: 105155685-105155705UCCACUCCAGUUAUCAGUCA3103
54790_1_11348−chr4: 105155779-105155799AGCCAAUAUACUUCCUUAUU3104
54790_1_11349−chr4: 105155780-105155800AAGCCAAUAUACUUCCUUAU3105
54790_1_11359−chr4: 105155909-105155929CUAACAUGAGCAUCUAUCUU3106
54790_1_11360−chr4: 105155910-105155930UCUAACAUGAGCAUCUAUCU3107
54790_1_11365−chr4: 105155933-105155953CACUACACCAACUUCUUAAU3108
54790_1_11366−chr4: 105155934-105155954UCACUACACCAACUUCUUAA3109
54790_1_11379−chr4: 105155998-105156018AGCUAGUCAUUUCUCCAGUA3110
54790_1_11394−chr4: 105156064-105156084AAAUUUAUAGUCAGCUGAGG3111
54790_1_11395−chr4: 105156067-105156087CAAAAAUUUAUAGUCAGCUG3112
54790_1_11405−chr4: 105156101-105156121GAACAACUUUUUUAAAAUUA3113
54790_1_11417−chr4: 105156168-105156188GAGAACAGAUUUACAUUUUU3114
54790_1_11435−chr4: 105156265-105156285CAUUUUUCUUCUUUUGAAUA3115
54790_1_11446−chr4: 105156333-105156353GCAUUUCUAUGCCUGAACAU3116
54790_1_11449−chr4: 105156379-105156399AAAAAUAUCAAUACUCUGUA3117
54790_1_11462−chr4: 105156490-105156510GGUUUUAGCAAUGGCUAAUG3118
54790_1_11466−chr4: 105156499-105156519GGUAAGGCAGGUUUUAGCAA3119
54790_1_11467−chr4: 105156511-105156531AAUAAGUGAUUUGGUAAGGC3120
54790_1_11468−chr4: 105156515-105156535AGAAAAUAAGUGAUUUGGUA3121
54790_1_11469−chr4: 105156520-105156540CAUCAAGAAAAUAAGUGAUU3122
54790_1_11477−chr4: 105156567-105156587GUUCUCAUUAAUGUAUAACC3123
54790_1_11482−chr4: 105156595-105156615UAAUAACCCAUUUGAGAGAU3124
54790_1_11483−chr4: 105156596-105156616AUAAUAACCCAUUUGAGAGA3125
54790_1_11497−chr4: 105156629-105156649UUUUAUGCAUCAUCUAUUUC3126
54790_1_11511−chr4: 105156686-105156706AUAUACCAUGCUAUGUUAUC3127
54790_1_11513−chr4: 105156717-105156737AGACAGGUAAGAAAAACGGG3128
54790_1_11517−chr4: 105156720-105156740UGCAGACAGGUAAGAAAAAC3129
54790_1_11519−chr4: 105156721-105156741GUGCAGACAGGUAAGAAAAA3130
54790_1_11523−chr4: 105156733-105156753GUGCCCUUCUUAGUGCAGAC3131
54790_1_11527−chr4: 105156755-105156775UAAUAAUUAUGGUAUUUAAU3132
54790_1_11528−chr4: 105156756-105156776CUAAUAAUUAUGGUAUUUAA3133
54790_1_11530−chr4: 105156766-105156786GGCAGCACAACUAAUAAUUA3134
54790_1_11533−chr4: 105156787-105156807AUUCUGGUGCUCUACUUCAG3135
54790_1_11537−chr4: 105156803-105156823AUUGUAUUACUCUCACAUUC3136
54790_1_11539−chr4: 105156830-105156850UUAUGGAUAGAAUCUGGGUG3137
54790_1_11540−chr4: 105156835-105156855GUAUGUUAUGGAUAGAAUCU3138
54790_1_11541−chr4: 105156836-105156856AGUAUGUUAUGGAUAGAAUC3139
54790_1_11545−chr4: 105156847-105156867AAGACCAGGACAGUAUGUUA3140
54790_1_11548−chr4: 105156861-105156881UUAAAAAAAUUAAUAAGACC3141
54790_1_11550−chr4: 105156884-105156904AAAGUGCUAAAAGAACAAAC3142
54790_1_11554−chr4: 105156908-105156928AAGAGACUUCAAACAAAAGC3143
54790_1_11562−chr4: 105156960-105156980UGAGAUAACUUUACAGCCAA3144
54790_1_11572−chr4: 105157034-105157054AAUCAUCUGAAUUAAUUACA3145
54790_1_11573−chr4: 105157035-105157055UAAUCAUCUGAAUUAAUUAC3146
54790_1_11587−chr4: 105157090-105157110UCUUCUGUUAUAAUGUAUAU3147
54790_1_11591−chr4: 105157118-105157138AGACACUGUAUUUGUAGAAA3148
54790_1_11612−chr4: 105157208-105157228UACAUUUGGUACAUUAAAAU3149
54790_1_11619−chr4: 105157222-105157242UUCUUUUCAUCAGUUACAUU3150
54790_1_11627−chr4: 105157250-105157270UUUUGAAAGGUACCCAUUUA3151
54790_1_11636−chr4: 105157263-105157283UUUUUUCCUUCAUUUUUGAA3152
54790_1_11647−chr4: 105157310-105157330ACUAAAAUAAAUAAUUUAUA3153
54790_1_11658−chr4: 105157389-105157409AAGAUAAAAUCUAUAAAACA3154
54790_1_11663−chr4: 105157416-105157436AACCAUUUCAGUGGCUAGAU3155
54790_1_11667−chr4: 105157425-105157445UGGAGAAAAAACCAUUUCAG3156
54790_1_11670−chr4: 105157445-105157465UGUAGAUAAUAUAACUUCAC3157
54790_1_11683−chr4: 105157515-105157535GUUUUUCCACAAGCGUAAUG3158
54790_1_11693−chr4: 105157581-105157601UUAAAUCUUAGCCAUUAAUA3159
54790_1_11713−chr4: 105157719-105157739UACGGUGACGUGAGGUCGGA3160
54790_1_11714−chr4: 105157720-105157740GUACGGUGACGUGAGGUCGG3161
54790_1_11718−chr4: 105157760-105157780GCGAACUUGGGUCUUCCUCC3162
54790_1_11719−chr4: 105157763-105157783UUAGCGAACUUGGGUCUUCC3163
54790_1_11723−chr4: 105157766-105157786CUCUUAGCGAACUUGGGUCU3164
54790_1_11730−chr4: 105157788-105157808CGAUGAGCCCUCCGACUCUG3165
54790_1_11733−chr4: 105157798-105157818AUAUUAGGGUCGAUGAGCCC3166
54790_1_11735−chr4: 105157801-105157821CGGAUAUUAGGGUCGAUGAG3167
54790_1_11737−chr4: 105157802-105157822ACGGAUAUUAGGGUCGAUGA3168
54790_1_11740−chr4: 105157825-105157845UUAAUCGGUCCGUACCACCG3169
54790_1_11741−chr4: 105157829-105157849GUUUUUAAUCGGUCCGUACC3170
54790_1_11742−chr4: 105157832-105157852UACGUUUUUAAUCGGUCCGU3171
54790_1_11743−chr4: 105157837-105157857AUUUUUACGUUUUUAAUCGG3172
54790_1_11748−chr4: 105157877-105157897GCUCUGGUCGGAUCGGAUGU3173
54790_1_11750−chr4: 105157904-105157924CCCCACCUAGUGAUCUCCAG3174
54790_1_11753−chr4: 105157909-105157929UCUUCCCCCACCUAGUGAUC3175
54790_1_11757−chr4: 105157920-105157940GAAAUCCUUCGUCUUCCCCC3176
54790_1_11759−chr4: 105157923-105157943CGUGAAAUCCUUCGUCUUCC3177
54790_1_11760−chr4: 105157924-105157944UCGUGAAAUCCUUCGUCUUC3178
54790_1_11761−chr4: 105157925-105157945GUCGUGAAAUCCUUCGUCUU3179
54790_1_11763−chr4: 105157926-105157946GGUCGUGAAAUCCUUCGUCU3180
54790_1_11768−chr4: 105157936-105157956CGGACAUUAGGGUCGUGAAA3181
54790_1_11772−chr4: 105157964-105157984AAAUAAGUUCCGGUCCGGCU3182
54790_1_11774−chr4: 105157971-105157991UAACAGUAAAUAAGUUCCGG3183
54790_1_11775−chr4: 105157976-105157996AGUUGUAACAGUAAAUAAGU3184
54790_1_11802−chr4: 105158114-105158134CCCAUGCUCUUGAAAAAUGU3185
54790_1_11824−chr4: 105158282-105158302CCCAAAAACCCCGAGGAUUA3186
54790_1_11825−chr4: 105158289-105158309AUAGUUUCCCAAAAACCCCG3187
54790_1_11849−chr4: 105158415-105158435UUCAUUAUAUCUUUUACAAU3188
54790_1_11850−chr4: 105158416-105158436AUUCAUUAUAUCUUUUACAA3189
54790_1_11859−chr4: 105158456-105158476UUUUACCUCUCUUCCUAUCU3190
54790_1_11865−chr4: 105158493-105158513CAAUGGCUUUCCUUGGGUGA3191
54790_1_11870−chr4: 105158499-105158519AGUAUUCAAUGGCUUUCCUU3192
54790_1_11871−chr4: 105158500-105158520CAGUAUUCAAUGGCUUUCCU3193
54790_1_11873−chr4: 105158510-105158530AUGACCCAUUCAGUAUUCAA3194
54790_1_11881−chr4: 105158578-105158598ACCAGAGAUAUACACUAAGU3195
54790_1_11888−chr4: 105158618-105158638AGUGUAAACUGAGAUAUUAU3196
54790_1_11889−chr4: 105158619-105158639CAGUGUAAACUGAGAUAUUA3197
54790_1_11904−chr4: 105158668-105158688UUUCUACUUCCUCUAUUUGC3198
54790_1_11917−chr4: 105158729-105158749UGCUCUACCUAAUUCAAUUU3199
54790_1_11944−chr4: 105158802-105158822AAAAAAAAAAACCAAAAAAG3200
54790_1_11955−chr4: 105158847-105158867AAGGAAUUAUCACUAACUAA3201
54790_1_11956−chr4: 105158848-105158868CAAGGAAUUAUCACUAACUA3202
54790_1_11958−chr4: 105158866-105158886AAAUGAGCAUACAGAUGUCA3203
54790_1_11969−chr4: 105158895-105158915AAGAGAAGCCUACUAUUUUU3204
54790_1_11976−chr4: 105158941-105158961UGUGACCGCGUGUAACUGGA3205
54790_1_11979−chr4: 105158945-105158965UUGAUGUGACCGCGUGUAAC3206
54790_1_11984−chr4: 105158985-105159005AAAUACUGCUGCCACGUGCA3207
54790_1_11985−chr4: 105159015-105159035GAGUCUCUGGAAUCCUAGGA3208
54790_1_11987−chr4: 105159019-105159039AUAAGAGUCUCUGGAAUCCU3209
54790_1_11989−chr4: 105159028-105159048CACUGUUACAUAAGAGUCUC3210
54790_1_11998−chr4: 105159109-105159129CAGAGCCAGACAAGGGCUCC3211
54790_1_12000−chr4: 105159116-105159136ACCCUAUCAGAGCCAGACAA3212
54790_1_12002−chr4: 105159117-105159137GACCCUAUCAGAGCCAGACA3213
54790_1_12008−chr4: 105159145-105159165GACCUAAACACCUUGAUCUU3214
54790_1_12013−chr4: 105159176-105159196GGUAGGAAAACCAUGCGUUA3215
54790_1_12014−chr4: 105159177-105159197UGGUAGGAAAACCAUGCGUU3216
54790_1_12020−chr4: 105159193-105159213ACAGCUUUUGAGGCUUUGGU3217
54790_1_12025−chr4: 105159197-105159217AGGCACAGCUUUUGAGGCUU3218
54790_1_12027−chr4: 105159203-105159223GUAUUUAGGCACAGCUUUUG3219
54790_1_12030−chr4: 105159217-105159237AAAAGAUUAAUCUUGUAUUU3220
54790_1_12038−chr4: 105159295-105159315CGCGGUGACGUGAGGUUGGA3221
54790_1_12040−chr4: 105159317-105159337CAACGUCACUCGGCUCUAGC3222
54790_1_12044−chr4: 105159339-105159359GCGAACUUGGCCACUCCGCC3223
54790_1_12046−chr4: 105159342-105159362UUAGCGAACUUGGCCACUCC3224
54790_1_12048−chr4: 105159345-105159365CUCUUAGCGAACUUGGCCAC3225
54790_1_12050−chr4: 105159350-105159370CCGACCUCUUAGCGAACUUG3226
54790_1_12054−chr4: 105159367-105159387CGAUGAACCCACAGACUCCG3227
54790_1_12057−chr4: 105159371-105159391GGGUCGAUGAACCCACAGAC3228
54790_1_12059−chr4: 105159380-105159400CGGAUAUUAGGGUCGAUGAA3229
54790_1_12060−chr4: 105159381-105159401ACGGAUAUUAGGGUCGAUGA3230
54790_1_12063−chr4: 105159408-105159428UGUUUUAAUCGGCCCGCACC3231
54790_1_12064−chr4: 105159411-105159431UUAUGUUUUAAUCGGCCCGC3232
54790_1_12065−chr4: 105159416-105159436GAUUUUUAUGUUUUAAUCGG3233
54790_1_12066−chr4: 105159417-105159437UGAUUUUUAUGUUUUAAUCG3234
54790_1_12070−chr4: 105159455-105159475GUUGUGGUCCGACUGGUUGU3235
54790_1_12074−chr4: 105159468-105159488AUUCAGCCCUCAAGUUGUGG3236
54790_1_12076−chr4: 105159482-105159502GUUCGCCUAGUGGAAUUCAG3237
54790_1_12077−chr4: 105159483-105159503CGUUCGCCUAGUGGAAUUCA3238
54790_1_12082−chr4: 105159498-105159518GAAACCCCCCGGCUUCGUUC3239
54790_1_12085−chr4: 105159511-105159531ACAUUAGGGUCGUGAAACCC3240
54790_1_12086−chr4: 105159512-105159532GACAUUAGGGUCGUGAAACC3241
54790_1_12087−chr4: 105159513-105159533GGACAUUAGGGUCGUGAAAC3242
54790_1_12090−chr4: 105159514-105159534CGGACAUUAGGGUCGUGAAA3243
54790_1_12092−chr4: 105159515-105159535UCGGACAUUAGGGUCGUGAA3244
54790_1_12096−chr4: 105159542-105159562UUAAUCUUACGACCCGCGCC3245
54790_1_12097−chr4: 105159545-105159565AGAUUAAUCUUACGACCCGC3246
54790_1_12098−chr4: 105159550-105159570UAAAAAGAUUAAUCUUACGA3247
54790_1_12099−chr4: 105159551-105159571AUAAAAAGAUUAAUCUUACG3248
54790_1_12106−chr4: 105159575-105159595AUGACUAGUUGUUUGCUGCA3249
54790_1_12107−chr4: 105159576-105159596CAUGACUAGUUGUUUGCUGC3250
54790_1_12111−chr4: 105159599-105159619CCCAAAUCACAAAAAUGGUU3251
54790_1_12112−chr4: 105159604-105159624GUUUCCCCAAAUCACAAAAA3252
54790_1_12120−chr4: 105159696-105159716AUUUUGUGAGGCUGGGAGGC3253
54790_1_12123−chr4: 105159700-105159720AGGCAUUUUGUGAGGCUGGG3254
54790_1_12127−chr4: 105159703-105159723UAAAGGCAUUUUGUGAGGCU3255
54790_1_12130−chr4: 105159704-105159724UUAAAGGCAUUUUGUGAGGC3256
54790_1_12132−chr4: 105159708-105159728UUUUUUAAAGGCAUUUUGUG3257
54790_1_12134−chr4: 105159720-105159740CGGAAGAUGUAAUUUUUUAA3258
54790_1_12136−chr4: 105159742-105159762UAAUGUCCGCACUCGGUAGG3259
54790_1_12138−chr4: 105159757-105159777AGGGUUUUACGGCCCUAAUG3260
54790_1_12140−chr4: 105159765-105159785GGAACCGGAGGGUUUUACGG3261
54790_1_12141−chr4: 105159766-105159786CGGAACCGGAGGGUUUUACG3262
54790_1_12145−chr4: 105159782-105159802GCUAGAGAACGGUGGGCGGA3263
54790_1_12150−chr4: 105159812-105159832CCCAAAAGUGGCACAACCGG3264
54790_1_12153−chr4: 105159817-105159837CUCUGCCCAAAAGUGGCACA3265
54790_1_12161−chr4: 105159832-105159852AAACAUAAAAAUCGUCUCUG3266
54790_1_12162−chr4: 105159833-105159853AAAACAUAAAAAUCGUCUCU3267
54790_1_12166−chr4: 105159880-105159900AGGGUUCAUCGACCCUAAUG3268
54790_1_12167−chr4: 105159888-105159908GGUGUCAGAGGGUUCAUCGA3269
54790_1_12169−chr4: 105159889-105159909CGGUGUCAGAGGGUUCAUCG3270
54790_1_12172−chr4: 105159927-105159947UGACGUUGGAGGCGGAGGGC3271
54790_1_12173−chr4: 105159928-105159948GUGACGUUGGAGGCGGAGGG3272
54790_1_12174−chr4: 105159929-105159949AGUGACGUUGGAGGCGGAGG3273
54790_1_12177−chr4: 105159953-105159973CCUCACGUCACCGCGCUAGA3274
54790_1_12179−chr4: 105159964-105159984CAGCGGUCCGACCUCACGUC3275
54790_1_12180−chr4: 105159974-105159994CAGAGCAAGACAGCGGUCCG3276
54790_1_12183−chr4: 105159978-105159998GCCUCAGAGCAAGACAGCGG3277
54790_1_12196−chr4: 105159998-105160018GAAAAAAAAAAAAAGACUCU3278
54790_1_12213−chr4: 105160069-105160089CUGGUCAGACCGUUUAGUUU3279
54790_1_12215−chr4: 105160070-105160090UCUGGUCAGACCGUUUAGUU3280
54790_1_12222−chr4: 105160088-105160108GAGUUUUCUUGAGUGUUUUC3281
54790_1_12226−chr4: 105160126-105160146GCAGGUAUAAUGGUAUACUA3282
54790_1_12229−chr4: 105160136-105160156AAGGGGAGAGGCAGGUAUAA3283
54790_1_12230−chr4: 105160144-105160164GAUGGGGAAAGGGGAGAGGC3284
54790_1_12233−chr4: 105160148-105160168AGAGGAUGGGGAAAGGGGAG3285
54790_1_12235−chr4: 105160153-105160173UUUACAGAGGAUGGGGAAAG3286
54790_1_12237−chr4: 105160154-105160174AUUUACAGAGGAUGGGGAAA3287
54790_1_12239−chr4: 105160155-105160175AAUUUACAGAGGAUGGGGAA3288
54790_1_12243−chr4: 105160160-105160180GAGAGAAUUUACAGAGGAUG3289
54790_1_12246−chr4: 105160161-105160181UGAGAGAAUUUACAGAGGAU3290
54790_1_12247−chr4: 105160162-105160182UUGAGAGAAUUUACAGAGGA3291
54790_1_12250−chr4: 105160166-105160186AAGGUUGAGAGAAUUUACAG3292
54790_1_12258−chr4: 105160185-105160205AUGAAAUUAAAAAUGAGAGA3293
54790_1_12270−chr4: 105160209-105160229GUUGUUUUAGCUCUAGGUCU3294
54790_1_12273−chr4: 105160215-105160235GUUGUUGUUGUUUUAGCUCU3295
54790_1_12279−chr4: 105160270-105160290AAAAAUCAAUUUGGGAUAGG3296
54790_1_12281−chr4: 105160273-105160293UCUAAAAAUCAAUUUGGGAU3297
54790_1_12283−chr4: 105160278-105160298AAAGCUCUAAAAAUCAAUUU3298
54790_1_12285−chr4: 105160279-105160299AAAAGCUCUAAAAAUCAAUU3299
54790_1_12309−chr4: 105160369-105160389AUACAUAUACCAAAUAUACG3300
54790_1_12327−chr4: 105160511-105160531AGGCAAGAAGGCUUCUAUUU3301
54790_1_12331−chr4: 105160523-105160543CAAUUCUUUGUUAGGCAAGA3302
54790_1_12334−chr4: 105160531-105160551UCUAAUUACAAUUCUUUGUU3303
54790_1_12354−chr4: 105160638-105160658GAUUUUUCCUAUCUUUAGAA3304
54790_1_12374−chr4: 105160722-105160742UGGUGCUUGGUUUAGCUCUU3305
54790_1_12377−chr4: 105160723-105160743UUGGUGCUUGGUUUAGCUCU3306
54790_1_12379−chr4: 105160735-105160755CAAAAAACAGAUUUGGUGCU3307
54790_1_12380−chr4: 105160742-105160762AAACCCCCAAAAAACAGAUU3308
54790_1_12382−chr4: 105160809-105160829UGAGGUCGGACCCGCUGUCU3309
54790_1_12385−chr4: 105160810-105160830GUGAGGUCGGACCCGCUGUC3310
54790_1_12388−chr4: 105160819-105160839CGAGGCGAAGUGAGGUCGGA3311
54790_1_12389−chr4: 105160820-105160840GCGAGGCGAAGUGAGGUCGG3312
54790_1_12393−chr4: 105160854-105160874UUGGGUCCUCCGCCUCCAAC3313
54790_1_12395−chr4: 105160860-105160880ACGACCUUGGGUCCUCCGCC3314
54790_1_12396−chr4: 105160863-105160883UUAACGACCUUGGGUCCUCC3315
54790_1_12399−chr4: 105160866-105160886CUCUUAACGACCUUGGGUCC3316
54790_1_12400−chr4: 105160869-105160889CGUCUCUUAACGACCUUGGG3317
54790_1_12404−chr4: 105160877-105160897UCGGACUCCGUCUCUUAACG3318
54790_1_12408−chr4: 105160891-105160911GGGUCGAUGAGGCUUCGGAC3319
54790_1_12413−chr4: 105160928-105160948GUUUUUAAUCGGCCCGCACC3320
54790_1_12414−chr4: 105160931-105160951UAUGUUUUUAAUCGGCCCGC3321
54790_1_12415−chr4: 105160936-105160956AUUUUUAUGUUUUUAAUCGG3322
54790_1_12416−chr4: 105160937-105160957GAUUUUUAUGUUUUUAAUCG3323
54790_1_12419−chr4: 105160976-105160996GUUUUGGUCGGACUGGUUCU3324
54790_1_12420−chr4: 105161003-105161023CCGCUCACCUAGUGGUCCAG3325
54790_1_12423−chr4: 105161008-105161028CGACUCCGCUCACCUAGUGG3326
54790_1_12426−chr4: 105161017-105161037GAAACCCUCCGACUCCGCUC3327
54790_1_12429−chr4: 105161024-105161044GGGUCGUGAAACCCUCCGAC3328
54790_1_12431−chr4: 105161030-105161050ACAUUAGGGUCGUGAAACCC3329
54790_1_12433−chr4: 105161033-105161053UGGACAUUAGGGUCGUGAAA3330
54790_1_12434−chr4: 105161034-105161054GUGGACAUUAGGGUCGUGAA3331
54790_1_12449−chr4: 105161122-105161142CUAUAUGUGAAUAAUAGAUU3332
54790_1_12455−chr4: 105161160-105161180GAACAGCUUUAGAUGUUAAA3333
54790_1_12467−chr4: 105161200-105161220AGUUAAAUAAGUCACUCUUU3334
54790_1_12480−chr4: 105161277-105161297AAUAUCUUUUCAUAUCCAGA3335
54790_1_12505−chr4: 105161462-105161482AGCUUUUACUAUUUAGGCCG3336
54790_1_12510−chr4: 105161468-105161488CACCCAAGCUUUUACUAUUU3337
54790_1_12512−chr4: 105161514-105161534GUAAUGGCUCUGCUCUGUGC3338
54790_1_12516−chr4: 105161530-105161550AGCUCGAGAGUGUUCAGUAA3339
54790_1_12525−chr4: 105161567-105161587UUAAUAUUCUAAUAUAAGAU3340
54790_1_12527−chr4: 105161596-105161616AAACAAAGGUCCGAGAAAGA3341
54790_1_12529−chr4: 105161597-105161617GAAACAAAGGUCCGAGAAAG3342
54790_1_12537−chr4: 105161610-105161630UAUGAUUUACUGUGAAACAA3343
54790_1_12577−chr4: 105161868-105161888AAAAUUUCCACAUUGCUCCU3344
54790_1_12589−chr4: 105161974-105161994UUUAACCAUUUCUACCAAAG3345
54790_1_12611−chr4: 105162061-105162081UGUGCACUUUCAACAUAUUA3346
54790_1_12612−chr4: 105162062-105162082CUGUGCACUUUCAACAUAUU3347
54790_1_12617−chr4: 105162088-105162108AGUUUAUACAAAAGACCCCA3348
54790_1_12623−chr4: 105162125-105162145GUGCCUCAGCUGUCUUCUAC3349
54790_1_12630−chr4: 105162147-105162167GUUUGUUUUGUGUGUGUGUU3350
54790_1_12639−chr4: 105162225-105162245GGAAGGCAUUAGGGUAACCU3351
54790_1_12640−chr4: 105162226-105162246GGGAAGGCAUUAGGGUAACC3352
54790_1_12645−chr4: 105162234-105162254GACCAUGUGGGAAGGCAUUA3353
54790_1_12646−chr4: 105162235-105162255UGACCAUGUGGGAAGGCAUU3354
54790_1_12648−chr4: 105162242-105162262AUGUGUUUGACCAUGUGGGA3355
54790_1_12650−chr4: 105162246-105162266CUCCAUGUGUUUGACCAUGU3356
54790_1_12651−chr4: 105162247-105162267GCUCCAUGUGUUUGACCAUG3357
54790_1_12657−chr4: 105162290-105162310AACUGCAGGCUUCAGAAUUC3358
54790_1_12661−chr4: 105162304-105162324UCCCACUGAUAAACAACUGC3359
54790_1_12669−chr4: 105162371-105162391UGUAUCAGUAUUCAUGAUCC3360
54790_1_12674−chr4: 105162411-105162431ACCAUGUUUCCCCUGCAGUC3361
54790_1_12677−chr4: 105162439-105162459GGCAGGGAAAAGCCUCCUUU3362
54790_1_12680−chr4: 105162455-105162475AAAAUAAACAGUGUGGGGCA3363
54790_1_12683−chr4: 105162456-105162476UAAAAUAAACAGUGUGGGGC3364
54790_1_12685−chr4: 105162460-105162480AGUUUAAAAUAAACAGUGUG3365
54790_1_12686−chr4: 105162461-105162481UAGUUUAAAAUAAACAGUGU3366
54790_1_12687−chr4: 105162462-105162482AUAGUUUAAAAUAAACAGUG3367
54790_1_12693−chr4: 105162493-105162513CAAAGUGAAAAGCUCCUUUC3368
54790_1_12701−chr4: 105162538-105162558AAGUGCCUACUUGCUUGUCA3369
54790_1_12702−chr4: 105162539-105162559AAAGUGCCUACUUGCUUGUC3370
54790_1_12710−chr4: 105162588-105162608AAAGAGAGUAACACUCCUCA3371
54790_1_12711−chr4: 105162589-105162609GAAAGAGAGUAACACUCCUC3372
54790_1_12720−chr4: 105162616-105162636UAAAAGAGUUUGAGUCAGCU3373
54790_1_12727−chr4: 105162660-105162680UGCAGCAACAUUAUUAGAGA3374
54790_1_12732−chr4: 105162685-105162705UGCUCCAACUGUUUCUAUGA3375
54790_1_12741−chr4: 105162767-105162787AUUUCUAUAUGUAAUAGGAA3376
54790_1_12745−chr4: 105162772-105162792GAAGUAUUUCUAUAUGUAAU3377
54790_1_12749−chr4: 105162794-105162814UCUAUACAAACAGUGAUUUU3378
54790_1_12752−chr4: 105162795-105162815UUCUAUACAAACAGUGAUUU3379
54790_1_12762−chr4: 105162852-105162872CCCCGUAUUAUUGCAGAUAU3380
54790_1_12765−chr4: 105162882-105162902AUUAAUCUAUCACACAAAAG3381
54790_1_12767−chr4: 105162883-105162903CAUUAAUCUAUCACACAAAA3382
54790_1_12769−chr4: 105162884-105162904UCAUUAAUCUAUCACACAAA3383
54790_1_12788−chr4: 105162983-105163003UCCAUGCUAAGCACAGCUGC3384
54790_1_12802−chr4: 105163012-105163032CUUUUUUUUCUCAUCCUUUU3385
54790_1_12822−chr4: 105163124-105163144UCUGAUAAUUUGUUACAAGU3386
54790_1_12826−chr4: 105163159-105163179AAAGAUGAAAAGCUCAAAAA3387
54790_1_12831−chr4: 105163184-105163204AGAAUUAAAUCUAUAAUUCA3388
54790_1_12832−chr4: 105163185-105163205CAGAAUUAAAUCUAUAAUUC3389
54790_1_12842−chr4: 105163296-105163316GAAAGUGGUGGCAAUCCAGG3390
54790_1_12843−chr4: 105163299-105163319AGUGAAAGUGGUGGCAAUCC3391
54790_1_12845−chr4: 105163308-105163328AAAUACUGGAGUGAAAGUGG3392
54790_1_12848−chr4: 105163311-105163331UUGAAAUACUGGAGUGAAAG3393
54790_1_12854−chr4: 105163322-105163342UGAAGUGUUUAUUGAAAUAC3394
54790_1_12869−chr4: 105163419-105163439UAGACAUUUACGUUCCUUAC3395
54790_1_12872−chr4: 105163420-105163440GUAGACAUUUACGUUCCUUA3396
54790_1_12874−chr4: 105163421-105163441AGUAGACAUUUACGUUCCUU3397
54790_1_12877−chr4: 105163426-105163446AAAAGAGUAGACAUUUACGU3398
54790_1_12887−chr4: 105163477-105163497AAUCGAACAAUGCGAUAAAC3399
54790_1_12899−chr4: 105163553-105163573AGAAACCUUUCACGAAUCGU3400
54790_1_12901−chr4: 105163569-105163589GUAUUCUUAAUCUAUUAGAA3401
54790_1_12911−chr4: 105163623-105163643CAAAGAAGGAAUCAUUUCAC3402
54790_1_12918−chr4: 105163645-105163665UCAAUAAAUUGGGGUACAGA3403
54790_1_12923−chr4: 105163669-105163689AAGAUAAUUCAAAAUUUAAU3404
54790_1_12925−chr4: 105163670-105163690AAAGAUAAUUCAAAAUUUAA3405
54790_1_12929−chr4: 105163703-105163723ACAAUGGAGAUUUGCAAAUA3406
54790_1_12931−chr4: 105163704-105163724GACAAUGGAGAUUUGCAAAU3407
54790_1_12936−chr4: 105163719-105163739GAUUACGAACAAAGAGACAA3408
54790_1_12949−chr4: 105163772-105163792CCAAACACCAGACUGCUUGU3409
54790_1_12957−chr4: 105163892-105163912GUUAAUAUGGAGUUGUUUCG3410
54790_1_12965−chr4: 105163928-105163948GAAUUUACACAUGUCAAAAC3411
54790_1_12971−chr4: 105164016-105164036UUUUUUACUGACUCUCCACU3412
54790_1_12973−chr4: 105164022-105164042UUUGUGUUUUUUACUGACUC3413
54790_1_12983−chr4: 105164088-105164108ACUGAUGUCAAUCAUGACAU3414
54790_1_12985−chr4: 105164111-105164131ACCUCUAGAUUACAUGUCGU3415
54790_1_12988−chr4: 105164131-105164151CUACUUAUAAAUUAUGUAAG3416
54790_1_12997−chr4: 105164176-105164196UCCCCUUUAUCCAAACAGUU3417
54790_1_12999−chr4: 105164187-105164207CCGACCCAUCAUCCCCUUUA3418
54790_1_13001−chr4: 105164194-105164214ACGGUACCCGACCCAUCAUC3419
54790_1_13003−chr4: 105164195-105164215AACGGUACCCGACCCAUCAU3420
54790_1_13005−chr4: 105164196-105164216CAACGGUACCCGACCCAUCA3421
54790_1_13008−chr4: 105164203-105164223GUACCACCAACGGUACCCGA3422
54790_1_13009−chr4: 105164204-105164224UGUACCACCAACGGUACCCG3423
54790_1_13011−chr4: 105164208-105164228UCAUUGUACCACCAACGGUA3424
54790_1_13012−chr4: 105164209-105164229CUCAUUGUACCACCAACGGU3425
54790_1_13014−chr4: 105164218-105164238UUUGCGUCUCUCAUUGUACC3426
54790_1_13015−chr4: 105164221-105164241GUAUUUGCGUCUCUCAUUGU3427
54790_1_13024−chr4: 105164263-105164283ACGUACUAGAGUGAAUAUAC3428
54790_1_13028−chr4: 105164308-105164328UCGAUUAUUUUUCCUUUCAG3429
54790_1_13031−chr4: 105164317-105164337CUGUAUGUGUCGAUUAUUUU3430
54790_1_13035−chr4: 105164352-105164372UUCGUCUAAGUGUUUACGAU3431
54790_1_13046−chr4: 105164380-105164400UAAUCAACAAGAGUAAAAUG3432
54790_1_13059−chr4: 105164459-105164479UUAAAACGGUUCAUUGUACG3433
54790_1_13070−chr4: 105164554-105164574UUCCAGAAGGGUAAAGAUGA3434
54790_1_13071−chr4: 105164566-105164586UGAGCCUGUAUAUUCCAGAA3435
54790_1_13073−chr4: 105164567-105164587AUGAGCCUGUAUAUUCCAGA3436
54790_1_13092−chr4: 105164675-105164695CGUCUCCGACCUUCGUAGGA3437
54790_1_13094−chr4: 105164676-105164696UCGUCUCCGACCUUCGUAGG3438
54790_1_13098−chr4: 105164687-105164707GUGUGGAAAACUCGUCUCCG3439
54790_1_13101−chr4: 105164691-105164711UUAAGUGUGGAAAACUCGUC3440
54790_1_13106−chr4: 105164714-105164734ACCGCGGAUAAGUCCGUUGA3441
54790_1_13107−chr4: 105164715-105164735GACCGCGGAUAAGUCCGUUG3442
54790_1_13110−chr4: 105164722-105164742CGGUUGAGACCGCGGAUAAG3443
54790_1_13111−chr4: 105164734-105164754ACUCUUUCGAUACGGUUGAG3444
54790_1_13116−chr4: 105164766-105164786UGAACACGUUAGAGGGACAG3445
54790_1_13120−chr4: 105164801-105164821GGGGAACUCGGUUAGAAGUC3446
54790_1_13126−chr4: 105164844-105164864CUAACUUUGUUAUUUUCCCU3447
54790_1_13129−chr4: 105164848-105164868AGAACUAACUUUGUUAUUUU3448
54790_1_13130−chr4: 105164849-105164869UAGAACUAACUUUGUUAUUU3449
54790_1_13135−chr4: 105164893-105164913UUUCCUACUAGUACUUUCCU3450
54790_1_13136−chr4: 105164897-105164917GUUAUUUCCUACUAGUACUU3451
54790_1_13141−chr4: 105164911-105164931CAUAGAUUAUUUCUGUUAUU3452
54790_1_13151−chr4: 105164955-105164975CGAUAGUAAAUUAUAAAGAU3453
54790_1_13159−chr4: 105165024-105165044CUUUUAUACUAUGUUUUAUC3454
54790_1_13168−chr4: 105165074-105165094GAUAGUAGAUAGAAAUUCGU3455
54790_1_13170−chr4: 105165097-105165117GUCCAGACUCGGUGGUGUGG3456
54790_1_13172−chr4: 105165116-105165136AGGGUUUCACGACCUUAAUG3457
54790_1_13174−chr4: 105165125-105165145CGGAGCCGGAGGGUUUCACG3458
54790_1_13176−chr4: 105165141-105165161GAGUCCACUAGACGGGCGGA3459
54790_1_13180−chr4: 105165158-105165178CCAAAGUUUGAGGACUGGAG3460
54790_1_13184−chr4: 105165179-105165199AAAGAGAUGCAACCGGUCCA3461
54790_1_13185−chr4: 105165183-105165203CCCCAAAGAGAUGCAACCGG3462
54790_1_13187−chr4: 105165188-105165208GUCUGCCCCAAAGAGAUGCA3463
54790_1_13196−chr4: 105165202-105165222ACAUAAAAAACCAUGUCUGC3464
54790_1_13197−chr4: 105165203-105165223AACAUAAAAAACCAUGUCUG3465
54790_1_13198−chr4: 105165204-105165224AAACAUAAAAAACCAUGUCU3466
54790_1_13201−chr4: 105165213-105165233ACCGAUUAAAAACAUAAAAA3467
54790_1_13203−chr4: 105165233-105165253GUCCGCGGGUGGUGGUGCGG3468
54790_1_13204−chr4: 105165252-105165272AGGACUCACCGACCUUAAUG3469
54790_1_13205−chr4: 105165261-105165281CGGAGUCAGAGGACUCACCG3470
54790_1_13209−chr4: 105165265-105165285AGCACGGAGUCAGAGGACUC3471
54790_1_13212−chr4: 105165300-105165320GUGACGUUGGAGACGGAGGA3472
54790_1_13213−chr4: 105165301-105165321AGUGACGUUGGAGACGGAGG3473
54790_1_13215−chr4: 105165336-105165356AGUGGGUCCGACCUCACGUU3474
54790_1_13217−chr4: 105165346-105165366AGAGGGAGACAGUGGGUCCG3475
54790_1_13219−chr4: 105165350-105165370CUUCAGAGGGAGACAGUGGG3476
54790_1_13236−chr4: 105165377-105165397UAAAAAAUAAAAAUAAAAAA3477
54790_1_13238−chr4: 105165378-105165398AUAAAAAAUAAAAAUAAAAA3478
54790_1_13244−chr4: 105165429-105165449AUUCCUUAAAGGUGAGAGUG3479
54790_1_13249−chr4: 105165447-105165467AAAGUACUGUGACGGUACAU3480
54790_1_13254−chr4: 105165477-105165497GAGUUUUUGUAGAAAGUGUA3481
54790_1_13255−chr4: 105165478-105165498UGAGUUUUUGUAGAAAGUGU3482
54790_1_13281−chr4: 105165615-105165635GCUUGCGUGAUAAUUGUUGU3483
54790_1_13283−chr4: 105165616-105165636UGCUUGCGUGAUAAUUGUUG3484
54790_1_13288−chr4: 105165652-105165672UCAUCAGUAAGUGUUAUUGA3485
54790_1_13289−chr4: 105165653-105165673AUCAUCAGUAAGUGUUAUUG3486
54790_1_13293−chr4: 105165681-105165701AGAGUAUCCCAACUUAUACA3487
54790_1_13298−chr4: 105165710-105165730CCCUAAAUGCAGACUUAGAA3488
54790_1_13310−chr4: 105165777-105165797UACAUUUUGAAAAGUCACUG3489
54790_1_13323−chr4: 105165848-105165868AUUGUGGGUAAGAAUAAUAA3490
54790_1_13330−chr4: 105165863-105165883UUAAAGCAAUGCAUUAUUGU3491
54790_1_13331−chr4: 105165864-105165884UUUAAAGCAAUGCAUUAUUG3492
54790_1_13333−chr4: 105165908-105165928UCAUCUCUGAGUCUUUCCAU3493
54790_1_13335−chr4: 105165913-105165933AUGUAUCAUCUCUGAGUCUU3494
54790_1_13344−chr4: 105165963-105165983CCGUCCUUUUCUUUUCAUCG3495
54790_1_13349−chr4: 105165980-105166000AUGUCCUCAACUGUCUUCCG3496
54790_1_13352−chr4: 105165984-105166004CCUUAUGUCCUCAACUGUCU3497
54790_1_13355−chr4: 105165997-105166017CUUCAUUACUAUACCUUAUG3498
54790_1_13361−chr4: 105166005-105166025UCGUUAUUCUUCAUUACUAU3499
54790_1_13388−chr4: 105166127-105166147UUAAAAUAAAUAAUGUUAGU3500
54790_1_13394−chr4: 105166160-105166180UGUACAAGUUGGUAUGACGA3501
54790_1_13403−chr4: 105166201-105166221UUCGAUUUAAAAUCACAGUG3502
54790_1_13415−chr4: 105166265-105166285ACUGUUUCUUAAAUCGUUUU3503
54790_1_13418−chr4: 105166266-105166286AACUGUUUCUUAAAUCGUUU3504
54790_1_13425−chr4: 105166289-105166309AAAAAUGUGGCAUAAUUUUG3505
54790_1_13428−chr4: 105166302-105166322AUGUGAAAGAAACAAAAAUG3506
54790_1_13436−chr4: 105166340-105166360AAGAAAAAUUGAAUGCUUAC3507
54790_1_13454−chr4: 105166450-105166470AGUGUAUUUCAUUCAUCAAA3508
54790_1_13468−chr4: 105166528-105166548AAGCAAUAAUAGACAUAGCC3509
54790_1_13497−chr4: 105166671-105166691UCCUUUUUAUAUUCCGUAAA3510
54790_1_13499−chr4: 105166679-105166699CAUGAUAUUCCUUUUUAUAU3511
54790_1_13502−chr4: 105166691-105166711AUUAAAUACUUACAUGAUAU3512
54790_1_13512−chr4: 105166726-105166746UCUUUUAAUGAAACUUAAAU3513
54790_1_13519−chr4: 105166781-105166801GUAUUCGUUAGGAUCUACUU3514
54790_1_13520−chr4: 105166782-105166802AGUAUUCGUUAGGAUCUACU3515
54790_1_13524−chr4: 105166820-105166840AUUUUUUCUGUCUUAGUCUG3516
54790_1_13526−chr4: 105166855-105166875AGGAUUAUUUGUAUACUUAU3517
54790_1_13529−chr4: 105166856-105166876UAGGAUUAUUUGUAUACUUA3518
54790_1_13540−chr4: 105166903-105166923AAAUUGUCUCGGUAUAGACC3519
54790_1_13543−chr4: 105166906-105166926GUAAAAUUGUCUCGGUAUAG3520
54790_1_13557−chr4: 105166975-105166995UUCAUGGAAUUCGAUUUAUU3521
54790_1_13559−chr4: 105167003-105167023UCUUUAUUAGUUUCCAUGUU3522
54790_1_13562−chr4: 105167011-105167031UUCUUCCUUCUUUAUUAGUU3523
54790_1_13564−chr4: 105167027-105167047UUCUAUCCCACUUUUUUUCU3524
54790_1_13573−chr4: 105167041-105167061UGUACUCAAAGUAUUUCUAU3525
54790_1_13574−chr4: 105167042-105167062UUGUACUCAAAGUAUUUCUA3526
54790_1_13582−chr4: 105167112-105167132UUGUCUACUUUUUAUACACU3527
54790_1_13597−chr4: 105167194-105167214UCUUAUCUUUUACCUGAAGA3528
54790_1_13599−chr4: 105167203-105167223UAGUUAGUCUCUUAUCUUUU3529
54790_1_13611−chr4: 105167241-105167261UAUGAUUUGAGCCACGAUUA3530
54790_1_13635−chr4: 105167319-105167339UAUUGUUUUUAGAUAUAGUU3531
54790_1_13657−chr4: 105167551-105167571AGCACUGUUAUUUUUAAAAG3532
54790_1_13658−chr4: 105167552-105167572UAGCACUGUUAUUUUUAAAA3533
54790_1_13660−chr4: 105167553-105167573CUAGCACUGUUAUUUUUAAA3534
54790_1_13671−chr4: 105167628-105167648UACUAAAGCAUUAUUAUUGA3535
54790_1_13672−chr4: 105167629-105167649AUACUAAAGCAUUAUUAUUG3536
54790_1_13676−chr4: 105167659-105167679CACAGUCACUGACUAUGCCU3537
54790_1_13677−chr4: 105167660-105167680GCACAGUCACUGACUAUGCC3538
54790_1_13679−chr4: 105167690-105167710CAGGAUGAACUGCUACUGCU3539
54790_1_13684−chr4: 105167709-105167729GUUACACCUUAGAUCUGUAC3540
54790_1_13688−chr4: 105167748-105167768GACAACCAAAGAAUCUCCAA3541
54790_1_13689−chr4: 105167749-105167769AGACAACCAAAGAAUCUCCA3542
54790_1_13696−chr4: 105167784-105167804CUGUUAUUGAACAGCAAGAU3543
54790_1_13712−chr4: 105167845-105167865UUUAAAGACUGUUAAGCAGU3544
54790_1_13716−chr4: 105167846-105167866UUUUAAAGACUGUUAAGCAG3545
54790_1_13722−chr4: 105167881-105167901AGGCAAGAUUACGUCCUUAC3546
54790_1_13723−chr4: 105167882-105167902UAGGCAAGAUUACGUCCUUA3547
54790_1_13730−chr4: 105167901-105167921UUCCUUCAUUCCUUAAAGCU3548
54790_1_13740−chr4: 105167960-105167980CUCAGUUGUCUUGUACAACC3549
54790_1_13743−chr4: 105167963-105167983CAUCUCAGUUGUCUUGUACA3550
54790_1_13750−chr4: 105167985-105168005UCUAGGACUUAUAUGAAAUG3551
54790_1_13755−chr4: 105168020-105168040CCUCUACCUUUAACCACUUU3552
54790_1_13758−chr4: 105168028-105168048CAAACUUACCUCUACCUUUA3553
54790_1_13760−chr4: 105168035-105168055CUUCCACCAAACUUACCUCU3554
54790_1_13762−chr4: 105168041-105168061UGUGUACUUCCACCAAACUU3555
54790_1_13769−chr4: 105168050-105168070AAGUUUCAUUGUGUACUUCC3556
54790_1_13770−chr4: 105168053-105168073GAAAAGUUUCAUUGUGUACU3557
54790_1_13773−chr4: 105168084-105168104UUUGUCCCUUUGGGUACUGU3558
54790_1_13774−chr4: 105168085-105168105CUUUGUCCCUUUGGGUACUG3559
54790_1_13777−chr4: 105168099-105168119CCCCUCGUUUCGAUCUUUGU3560
54790_1_13779−chr4: 105168100-105168120CCCCCUCGUUUCGAUCUUUG3561
54790_1_13783−chr4: 105168118-105168138GGGUGCCACUCCAUUCUUCC3562
54790_1_13786−chr4: 105168119-105168139UGGGUGCCACUCCAUUCUUC3563
54790_1_13787−chr4: 105168120-105168140UUGGGUGCCACUCCAUUCUU3564
54790_1_13789−chr4: 105168121-105168141UUUGGGUGCCACUCCAUUCU3565
54790_1_13799−chr4: 105168129-105168149AACCCAUUUUUGGGUGCCAC3566
54790_1_13802−chr4: 105168134-105168154AAACAAACCCAUUUUUGGGU3567
54790_1_13804−chr4: 105168147-105168167CUAGUGAACUUAAAAACAAA3568
54790_1_13807−chr4: 105168148-105168168ACUAGUGAACUUAAAAACAA3569
54790_1_13817−chr4: 105168194-105168214UUACCAAAAUUCGUCUCCUC3570
54790_1_13819−chr4: 105168199-105168219GGUAAUUACCAAAAUUCGUC3571
54790_1_13823−chr4: 105168212-105168232CACUUUGUCUCUGGGUAAUU3572
54790_1_13831−chr4: 105168247-105168267CACCCAGUACUUUUCCCGAA3573
54790_1_13833−chr4: 105168253-105168273CCUGACCACCCAGUACUUUU3574
54790_1_13834−chr4: 105168254-105168274UCCUGACCACCCAGUACUUU3575
54790_1_13838−chr4: 105168265-105168285GUUAAGUGAACUCCUGACCA3576
54790_1_13839−chr4: 105168266-105168286GGUUAAGUGAACUCCUGACC3577
54790_1_13841−chr4: 105168269-105168289GUCGGUUAAGUGAACUCCUG3578
54790_1_13842−chr4: 105168274-105168294UUAUCGUCGGUUAAGUGAAC3579
54790_1_13847−chr4: 105168310-105168330CCCUCUUAUCACCGUUCUUU3580
54790_1_13851−chr4: 105168320-105168340UUAUCUUACUCCCUCUUAUC3581
54790_1_13853−chr4: 105168330-105168350UCCUUUAAUCUUAUCUUACU3582
54790_1_13855−chr4: 105168331-105168351UUCCUUUAAUCUUAUCUUAC3583
54790_1_13863−chr4: 105168350-105168370GGUCCUGUCGUUCUUUUGGU3584
54790_1_13868−chr4: 105168368-105168388UCCUACGAGAAGAACAACGG3585
54790_1_13870−chr4: 105168388-105168408ACGUUUCCGGACCUCCUUUU3586
54790_1_13872−chr4: 105168395-105168415GUCGUUCACGUUUCCGGACC3587
54790_1_13875−chr4: 105168398-105168418CUUGUCGUUCACGUUUCCGG3588
54790_1_13878−chr4: 105168403-105168423UCUCCCUUGUCGUUCACGUU3589
54790_1_13880−chr4: 105168420-105168440CCUUCCCACGAGGUCCUUCU3590
54790_1_13881−chr4: 105168421-105168441UCCUUCCCACGAGGUCCUUC3591
54790_1_13885−chr4: 105168427-105168447GAGACUUCCUUCCCACGAGG3592
54790_1_13888−chr4: 105168436-105168456GGACACCGAGAGACUUCCUU3593
54790_1_13889−chr4: 105168437-105168457UGGACACCGAGAGACUUCCU3594
54790_1_13891−chr4: 105168441-105168461GUUAUGGACACCGAGAGACU3595
54790_1_13895−chr4: 105168452-105168472UUUCUAUCUUUGUUAUGGAC3596
54790_1_13898−chr4: 105168475-105168495UGUGAGUUCCUCUCUAAUCU3597
54790_1_13906−chr4: 105168488-105168508GAGACUUUUUCAUUGUGAGU3598
54790_1_13913−chr4: 105168518-105168538UCUGAAUCUAUCUUACCAAU3599
54790_1_13915−chr4: 105168519-105168539UUCUGAAUCUAUCUUACCAA3600
54790_1_13918−chr4: 105168524-105168544CAGAGUUCUGAAUCUAUCUU3601
54790_1_13921−chr4: 105168555-105168575AAAAGAGAGAAAAUAAAGCA3602
54790_1_13930−chr4: 105168602-105168622GGACAAGGGGUUAUUGGAUA3603
54790_1_13932−chr4: 105168603-105168623UGGACAAGGGGUUAUUGGAU3604
54790_1_13937−chr4: 105168681-105168701CACAUAUGACGAGCCCACUA3605
54790_1_13938−chr4: 105168688-105168708CCCACUUCACAUAUGACGAG3606
54790_1_13939−chr4: 105168689-105168709UCCCACUUCACAUAUGACGA3607
54790_1_13942−chr4: 105168708-105168728CCUUAUUUUCUGAUGCUUAU3608
54790_1_13943−chr4: 105168709-105168729UCCUUAUUUUCUGAUGCUUA3609
54790_1_13946−chr4: 105168729-105168749UUUUCCCACCCUUCCCCCAC3610
54790_1_13950−chr4: 105168734-105168754UCCCCUUUUCCCACCCUUCC3611
54790_1_13951−chr4: 105168735-105168755GUCCCCUUUUCCCACCCUUC3612
54790_1_13952−chr4: 105168736-105168756AGUCCCCUUUUCCCACCCUU3613
54790_1_13955−chr4: 105168737-105168757GAGUCCCCUUUUCCCACCCU3614
54790_1_13957−chr4: 105168741-105168761CCCUGAGUCCCCUUUUCCCA3615
54790_1_13960−chr4: 105168742-105168762UCCCUGAGUCCCCUUUUCCC3616
54790_1_13962−chr4: 105168745-105168765AGAUCCCUGAGUCCCCUUUU3617
54790_1_13963−chr4: 105168746-105168766GAGAUCCCUGAGUCCCCUUU3618
54790_1_13965−chr4: 105168752-105168772UUACCUGAGAUCCCUGAGUC3619
54790_1_13968−chr4: 105168753-105168773GUUACCUGAGAUCCCUGAGU3620
54790_1_13970−chr4: 105168754-105168774UGUUACCUGAGAUCCCUGAG3621
54790_1_13972−chr4: 105168761-105168781CUUACUGUGUUACCUGAGAU3622
54790_1_13974−chr4: 105168762-105168782UCUUACUGUGUUACCUGAGA3623
54790_1_13976−chr4: 105168770-105168790UUCCGUAUUCUUACUGUGUU3624
54790_1_13979−chr4: 105168789-105168809CGAUGCGAUACUCCUACGUU3625
54790_1_13980−chr4: 105168798-105168818AUUCACCCUCGAUGCGAUAC3626
54790_1_13984−chr4: 105168813-105168833UAUACAAGAGUGAGUAUUCA3627
54790_1_13987−chr4: 105168814-105168834GUAUACAAGAGUGAGUAUUC3628
54790_1_13992−chr4: 105168849-105168869AUUCACUUCAUUGAGUCCCU3629
54790_1_13994−chr4: 105168853-105168873UAAGAUUCACUUCAUUGAGU3630
54790_1_13995−chr4: 105168854-105168874AUAAGAUUCACUUCAUUGAG3631
54790_1_14001−chr4: 105168884-105168904ACGUCACUGGACCUAUUCUG3632
54790_1_14005−chr4: 105168894-105168914AUUACCGUAAACGUCACUGG3633
54790_1_14007−chr4: 105168911-105168931GUAUUUUUCCUUACUUAAUU3634
54790_1_14010−chr4: 105168924-105168944UUAUGAUGAGUCGGUAUUUU3635
54790_1_14014−chr4: 105168947-105168967UGACACCAUAUAAAUAUUCU3636
54790_1_14018−chr4: 105168963-105168983CACUCAUCAAUUUCUUUGAC3637
54790_1_14021−chr4: 105168985-105169005GUUGGGUUUACGAGCAGUUA3638
54790_1_14026−chr4: 105169011-105169031UUAAACGUUAACGUUUUUAC3639
54790_1_14034−chr4: 105169085-105169105UGAUGACCCAUAGAUGGGUC3640
54790_1_14039−chr4: 105169099-105169119CUAGGUCGUUAGGGUGAUGA3641
54790_1_14040−chr4: 105169100-105169120ACUAGGUCGUUAGGGUGAUG3642
54790_1_14044−chr4: 105169158-105169178UCGGUGAUACCUUUUGUCAC3643
54790_1_14048−chr4: 105169170-105169190CAUUUGAUCAUGUCGGUGAU3644
54790_1_14051−chr4: 105169196-105169216UUGUGAAGAUGUGACGACCA3645
54790_1_14054−chr4: 105169197-105169217CUUGUGAAGAUGUGACGACC3646
54790_1_14056−chr4: 105169200-105169220UCUCUUGUGAAGAUGUGACG3647
54790_1_14062−chr4: 105169228-105169248UCAUCUGCAACCGUACCUAU3648
54790_1_14063−chr4: 105169234-105169254UUUUUAUCAUCUGCAACCGU3649
54790_1_14065−chr4: 105169239-105169259UUAGUUUUUUAUCAUCUGCA3650
54790_1_14068−chr4: 105169270-105169290UAUGAAAUGAGGACGUUCUU3651
54790_1_14072−chr4: 105169318-105169338AAGUUAUAGUGAUUACUAGU3652
54790_1_14075−chr4: 105169319-105169339CAAGUUAUAGUGAUUACUAG3653
54790_1_14085−chr4: 105169402-105169422AGGAUAGUUUUUCACCCGAU3654
54790_1_14087−chr4: 105169408-105169428UUUGUUAGGAUAGUUUUUCA3655
54790_1_14088−chr4: 105169409-105169429GUUUGUUAGGAUAGUUUUUC3656
54790_1_14092−chr4: 105169439-105169459CCUUGAGGUUGUUUAAUCGU3657
54790_1_14095−chr4: 105169460-105169480UGAUUAUAGAUCUUAGAUGU3658
54790_1_14099−chr4: 105169483-105169503UGUUAGAUACGUAGGCCGUU3659
54790_1_14101−chr4: 105169489-105169509UAGAAGUGUUAGAUACGUAG3660
54790_1_14104−chr4: 105169517-105169537UUUGUCUGUUGGGUGUCUCA3661
54790_1_14105−chr4: 105169518-105169538AUUUGUCUGUUGGGUGUCUC3662
54790_1_14109−chr4: 105169555-105169575UUCUCGGAGACGUGUCGUUA3663
54790_1_14116−chr4: 105169596-105169616GUUGUUUUUGUUUCUAUUUA3664
54790_1_14123−chr4: 105169654-105169674UGGGAAGAUCUGUAACCGAA3665
54790_1_14124−chr4: 105169660-105169680UCUUUUUGGGAAGAUCUGUA3666
54790_1_14132−chr4: 105169737-105169757UAUAUUUUUAGUUGAGUUCU3667
54790_1_14139−chr4: 105169806-105169826UGUUUACCACGACCCUAUCG3668
54790_1_14140−chr4: 105169814-105169834GGAUAAGUUGUUUACCACGA3669
54790_1_14142−chr4: 105169815-105169835GGGAUAAGUUGUUUACCACG3670
54790_1_14144−chr4: 105169821-105169841UCCUGUGGGAUAAGUUGUUU3671
54790_1_14146−chr4: 105169841-105169861UUUGUAUUUAAUCAUCCAUU3672
54790_1_14148−chr4: 105169847-105169867UUUGUUUUUGUAUUUAAUCA3673
54790_1_14157−chr4: 105169926-105169946AUCCAUGUCUCUGGUUACCC3674
54790_1_14158−chr4: 105169927-105169947UAUCCAUGUCUCUGGUUACC3675
54790_1_14161−chr4: 105169928-105169948UUAUCCAUGUCUCUGGUUAC3676
54790_1_14163−chr4: 105169929-105169949UUUAUCCAUGUCUCUGGUUA3677
54790_1_14165−chr4: 105169930-105169950UUUUAUCCAUGUCUCUGGUU3678
54790_1_14168−chr4: 105169945-105169965GUACCAUGACCAUAUUUUUA3679
54790_1_14169−chr4: 105169957-105169977UGUGGUUUUGUCGUACCAUG3680
54790_1_14170−chr4: 105169963-105169983GGUAUCUGUGGUUUUGUCGU3681
54790_1_14174−chr4: 105169986-105170006AAUGGACUGAAAUAUGAUCU3682
54790_1_14179−chr4: 105170019-105170039GAUUCGUGUUUCUUGUUUAA3683
54790_1_14180−chr4: 105170020-105170040UGAUUCGUGUUUCUUGUUUA3684
54790_1_14195−chr4: 105170100-105170120GGUAGUAAGAAGUGUCUUAA3685
54790_1_14203−chr4: 105170156-105170176AAGCAGAAACACUUUGCCAA3686
54790_1_14204−chr4: 105170157-105170177AAAGCAGAAACACUUUGCCA3687
54790_1_14212−chr4: 105170209-105170229GAGUAUCUUGAGUGUAGAUG3688
54790_1_14220−chr4: 105170275-105170295UGGUACACGAUCGGUGACAA3689
54790_1_14238−chr4: 105170369-105170389GGAGUCGGAAGUCUCAUCGA3690
54790_1_14240−chr4: 105170370-105170390CGGAGUCGGAAGUCUCAUCG3691
54790_1_14246−chr4: 105170403-105170423UGGGGUUUGAAAACUCUGAG3692
54790_1_14249−chr4: 105170446-105170466UGUUACGUCGUCGAUAAGUG3693
54790_1_14252−chr4: 105170471-105170491CCCAAGAGUGACACAACUGG3694
54790_1_14261−chr4: 105170491-105170511UGCCAAAAAAAAUUUCUCUA3695
54790_1_14263−chr4: 105170492-105170512UUGCCAAAAAAAAUUUCUCU3696
54790_1_14270−chr4: 105170555-105170575CAGCAGAGAAAAGACAACAC3697
54790_1_14279−chr4: 105170584-105170604UCUAUCUUCAAUUUCCAAUG3698
54790_1_14284−chr4: 105170615-105170635UUUCACCUAUAAAUAAUCAA3699
54790_1_14288−chr4: 105170652-105170672AUUGUCUCAGCUAUUCCUCA3700
54790_1_14293−chr4: 105170678-105170698UCCUCGGCUCCAGAAGCUCC3701
54790_1_14300−chr4: 105170694-105170714UUUAGUGACCAAUGUUUCCU3702
54790_1_14302−chr4: 105170720-105170740AGUACAGUUGCCAAUAUAAA3703
54790_1_14306−chr4: 105170748-105170768UGUAAUUGAAACACUAGCAU3704
54790_1_14317−chr4: 105170799-105170819CACAUCAUGUUUAUAUUUUG3705
54790_1_14326−chr4: 105170879-105170899GGCAGUGCUCAUCUUGCAGG3706
54790_1_14327−chr4: 105170882-105170902ACAGGCAGUGCUCAUCUUGC3707
54790_1_14330−chr4: 105170900-105170920GGAAGCAGAAGGAAGAACAC3708
54790_1_14334−chr4: 105170911-105170931GCUGAAAUAAAGGAAGCAGA3709
54790_1_14339−chr4: 105170921-105170941UAGACACACAGCUGAAAUAA3710
54790_1_14343−chr4: 105170944-105170964GUGUAGAAGGAGGAGGAAGU3711
54790_1_14346−chr4: 105170951-105170971UCUCCUAGUGUAGAAGGAGG3712
54790_1_14350−chr4: 105170954-105170974AUUUCUCCUAGUGUAGAAGG3713
54790_1_14353−chr4: 105170957-105170977GCAAUUUCUCCUAGUGUAGA3714
54790_1_14359−chr4: 105170987-105171007AUAGCAGAUGUUAAAGAUAU3715
54790_1_14370−chr4: 105171045-105171065UUAAAAAAAAAGAAUGAAGA3716
54790_1_14385−chr4: 105171110-105171130UUUGAGCCAGCAAUAACAGC3717
54790_1_14388−chr4: 105171135-105171155AAAUAACACUGAAAUGCUCC3718
54790_1_14393−chr4: 105171165-105171185GUCUUUACCUUGAGGGUAGU3719
54790_1_14398−chr4: 105171179-105171199GUGAAACUUAUUUUGUCUUU3720
54790_1_14402−chr4: 105171208-105171228GGUCCGUGACACGAUCUGUG3721
54790_1_14407−chr4: 105171226-105171246AAUAUCCGAAUAUUACACGG3722
54790_1_14408−chr4: 105171242-105171262UAGGUGAUCUAUUUGUAAUA3723
54790_1_14414−chr4: 105171270-105171290UGAUAAUUCUUUAAUAGUAU3724
54790_1_14431−chr4: 105171342-105171362UGCACUUCAUUUCCUUAGCA3725
54790_1_14441−chr4: 105171385-105171405UUCAGAAAGUUCUCUAUACU3726
54790_1_14458−chr4: 105171475-105171495AUGGCCUGUGUUAUCUUAUU3727
54790_1_14464−chr4: 105171494-105171514AUUUUUUAAAGAACAAAAGA3728
54790_1_14483−chr4: 105171572-105171592AUCUCAGUAAGUUACACUAC3729
54790_1_14490−chr4: 105171607-105171627UAGCAUCAAUACAGAAUUUA3730
54790_1_14495−chr4: 105171630-105171650GUAGCUCAAGAGUUGCAUCU3731
54790_1_14499−chr4: 105171658-105171678GACCAGCAUCCUUUAUCAAG3732
54790_1_14502−chr4: 105171680-105171700CAAACAUUACACUGGCAGCA3733
54790_1_14503−chr4: 105171681-105171701GCAAACAUUACACUGGCAGC3734
54790_1_14506−chr4: 105171688-105171708UAAAUGAGCAAACAUUACAC3735
54790_1_14514−chr4: 105171733-105171753UUCACCUUCUUCACCAUCCC3736
54790_1_14524−chr4: 105171785-105171805AGAGAAUAGUCUGUUUCUGU3737
54790_1_14529−chr4: 105171813-105171833UGAAAAUGAAUAAUGCAAUC3738
54790_1_14534−chr4: 105171840-105171860CUUCCAAAGCAGAUAAAGGC3739
54790_1_14535−chr4: 105171844-105171864UAGGCUUCCAAAGCAGAUAA3740
54790_1_14538−chr4: 105171863-105171883AUCUUGGAAGAUUAGGAAAU3741
54790_1_14540−chr4: 105171870-105171890AUGAUAAAUCUUGGAAGAUU3742
54790_1_14543−chr4: 105171879-105171899AUGAAGGUGAUGAUAAAUCU3743
54790_1_14545−chr4: 105171895-105171915UGCAUGCUAUGGACAUAUGA3744
54790_1_14548−chr4: 105171906-105171926UGUCUGAGAAAUGCAUGCUA3745
54790_1_14558−chr4: 105171991-105172011CAGUACCACAUGAAAAACCA3746
54790_1_14567−chr4: 105172023-105172043AAAUAUCUACUUCUUUGUCA3747
54790_1_14574−chr4: 105172054-105172074CACAGAAUGAAUAGAACGGG3748
54790_1_14587−chr4: 105172149-105172169CCCAGUUGACUAUUUAUUUA3749
54790_1_14590−chr4: 105172169-105172189AAUUGGAGGUACAAUAAGUU3750
54790_1_14591−chr4: 105172170-105172190GAAUUGGAGGUACAAUAAGU3751
54790_1_14598−chr4: 105172197-105172217AAAAACUGUCACGUCCCCCA3752
54790_1_14599−chr4: 105172201-105172221ACCUAAAAACUGUCACGUCC3753
54790_1_14601−chr4: 105172202-105172222CACCUAAAAACUGUCACGUC3754
54790_1_14603−chr4: 105172203-105172223ACACCUAAAAACUGUCACGU3755
54790_1_14604−chr4: 105172204-105172224UACACCUAAAAACUGUCACG3756
54790_1_14611−chr4: 105172221-105172241CCCCUCAGUUUUUAAUGUAC3757
54790_1_14616−chr4: 105172240-105172260AUAAUCAUCAAUUCAAAAAC3758
54790_1_14617−chr4: 105172241-105172261GAUAAUCAUCAAUUCAAAAA3759
54790_1_14619−chr4: 105172242-105172262CGAUAAUCAUCAAUUCAAAA3760
54790_1_14622−chr4: 105172264-105172284GUCCCGGAGGUCUGUUGUCG3761
54790_1_14624−chr4: 105172282-105172302UUGACACACACAAUAGUCGU3762
54790_1_14626−chr4: 105172283-105172303GUUGACACACACAAUAGUCG3763
54790_1_14655−chr4: 105172458-105172478UGAGUUCCACUUCUGUUGUU3764
54790_1_14662−chr4: 105172473-105172493GGAGAAGAAGUCGUAUGAGU3765
54790_1_14669−chr4: 105172524-105172544AGAAGGUGAAGACGGUGGGG3766
54790_1_14677−chr4: 105172566-105172586UUUAUGUCCAAACUUGACGU3767
54790_1_14681−chr4: 105172580-105172600UACCCAACUGGAAUUUUAUG3768
54790_1_14691−chr4: 105172629-105172649UUCAUUGAAAAAAAUUAACA3769
54790_1_14697−chr4: 105172664-105172684UAAACAUACAGGCAUUUGAA3770
54790_1_14702−chr4: 105172675-105172695AAUGUUUCUCAUAAACAUAC3771
54790_1_14742−chr4: 105172934-105172954GAGUAGCAGCAUAGCCAACU3772
54790_1_14760−chr4: 105173018-105173038CUAAAGGGAUAUUUAAAAUU3773
54790_1_14768−chr4: 105173033-105173053CAUAUUUUCUAUUCUCUAAA3774
54790_1_14769−chr4: 105173034-105173054UCAUAUUUUCUAUUCUCUAA3775
54790_1_14780−chr4: 105173077-105173097AGAAAAUUUAUAUUGUUGAG3776
54790_1_14796−chr4: 105173127-105173147AAACUUUUUAUCCUUUGUGU3777
54790_1_14801−chr4: 105173151-105173171UCCUCUUAGAAACUAAGGAU3778
54790_1_14802−chr4: 105173156-105173176CAUUUUCCUCUUAGAAACUA3779
54790_1_14811−chr4: 105173191-105173211GGUAACUGGCACACAGCAGA3780
54790_1_14816−chr4: 105173205-105173225GAACUUAUCGUUUUGGUAAC3781
54790_1_14818−chr4: 105173212-105173232UGAGUUGGAACUUAUCGUUU3782
54790_1_14819−chr4: 105173227-105173247UGUGGGUUGGAAGAUUGAGU3783
54790_1_14824−chr4: 105173261-105173281AGGGUUUCACGGCCCUAGUG3784
54790_1_14825−chr4: 105173269-105173289GGAGCCGGAGGGUUUCACGG3785
54790_1_14826−chr4: 105173270-105173290UGGAGCCGGAGGGUUUCACG3786
54790_1_14829−chr4: 105173286-105173306UCGAGCACUAGACGGGUGGA3787
54790_1_14835−chr4: 105173322-105173342AAAGUGGUAUAACCGGUCCG3788
54790_1_14836−chr4: 105173326-105173346CCCAAAAGUGGUAUAACCGG3789
54790_1_14838−chr4: 105173331-105173351CUCUGCCCAAAAGUGGUAUA3790
54790_1_14849−chr4: 105173346-105173366AAACAUAAAAAUCAUCUCUG3791
54790_1_14852−chr4: 105173347-105173367AAAACAUAAAAAUCAUCUCU3792
54790_1_14863−chr4: 105173390-105173410GCCCUCGUGUGGUGGUACGG3793
54790_1_14864−chr4: 105173391-105173411UGCCCUCGUGUGGUGGUACG3794
54790_1_14867−chr4: 105173409-105173429AGGGUUCAUCGACCCUGAUG3795
54790_1_14869−chr4: 105173410-105173430GAGGGUUCAUCGACCCUGAU3796
54790_1_14871−chr4: 105173417-105173437GGAGUCGGAGGGUUCAUCGA3797
54790_1_14872−chr4: 105173418-105173438CGGAGUCGGAGGGUUCAUCG3798
54790_1_14878−chr4: 105173457-105173477GUGACGUUGGAGGUGGAGGA3799
54790_1_14879−chr4: 105173458-105173478AGUGACGUUGGAGGUGGAGG3800
54790_1_14881−chr4: 105173482-105173502CCUCACGUCACCACGUUAGA3801
54790_1_14885−chr4: 105173493-105173513AACGGGUCCGACCUCACGUC3802
54790_1_14886−chr4: 105173503-105173523AGAGGGAGAAAACGGGUCCG3803
54790_1_14889−chr4: 105173507-105173527UCUCAGAGGGAGAAAACGGG3804
54790_1_14943−chr4: 105173722-105173742UAUUUGAAUAAAUGGGUUCC3805
54790_1_14944−chr4: 105173729-105173749UAAUAAAUAUUUGAAUAAAU3806
54790_1_14945−chr4: 105173730-105173750GUAAUAAAUAUUUGAAUAAA3807
54790_1_14966−chr4: 105173800-105173820UUAUAUGUCACUUUGUUAAC3808
54790_1_14989−chr4: 105173942-105173962UACAUCAUUUUUGCAUGCAU3809
54790_1_14990−chr4: 105173943-105173963AUACAUCAUUUUUGCAUGCA3810
54790_1_15001−chr4: 105174005-105174025UAUGUUGAUAGGGACAGCUA3811
54790_1_15006−chr4: 105174015-105174035UGUUAAUAUAUAUGUUGAUA3812
54790_1_15009−chr4: 105174016-105174036UUGUUAAUAUAUAUGUUGAU3813
54790_1_15018−chr4: 105174081-105174101AUAGAACAAAUUGAGGCUUU3814
54790_1_15019−chr4: 105174082-105174102UAUAGAACAAAUUGAGGCUU3815
54790_1_15021−chr4: 105174088-105174108UAUAGCUAUAGAACAAAUUG3816
54790_1_15040−chr4: 105174188-105174208GAUCUAUCAAAUUAAGGGAU3817
54790_1_15042−chr4: 105174193-105174213UUUAAGAUCUAUCAAAUUAA3818
54790_1_15044−chr4: 105174194-105174214UUUUAAGAUCUAUCAAAUUA3819
54790_1_15058−chr4: 105174271-105174291CAUAGUCUACUUCUCAAAAA3820
54790_1_15059−chr4: 105174272-105174292UCAUAGUCUACUUCUCAAAA3821
54790_1_15063−chr4: 105174310-105174330UAAAUCUUAGGAAAUACUAG3822
54790_1_15067−chr4: 105174322-105174342UUCUAUUCCAAAUAAAUCUU3823
54790_1_15119−chr4: 105174498-105174518AAGAGAUUAUAAACUACGUC3824
54790_1_15133−chr4: 105174565-105174585GGGUGUUUUUAAAAGGAACA3825
54790_1_15138−chr4: 105174590-105174610GUACAAAAGGAUGGACCGUG3826
54790_1_15140−chr4: 105174596-105174616UGUCAAGUACAAAAGGAUGG3827
54790_1_15154−chr4: 105174680-105174700GAAGGCAUUCACUCAGGAGG3828
54790_1_15158−chr4: 105174705-105174725CCAAUUUGAGUGUUUUCAUG3829
54790_1_15159−chr4: 105174726-105174746CAGUGACACUUGUGAGGACC3830
54790_1_15160−chr4: 105174729-105174749CAUCAGUGACACUUGUGAGG3831
54790_1_15174−chr4: 105174763-105174783AAGGAAAAGAAGAGGGGAAU3832
54790_1_15176−chr4: 105174764-105174784CAAGGAAAAGAAGAGGGGAA3833
54790_1_15180−chr4: 105174786-105174806ACGAGACUGUAUAAAGUUCU3834
54790_1_15186−chr4: 105174825-105174845UUUAUCAAAGUGAACUCUCG3835
54790_1_15192−chr4: 105174850-105174870UUAGGGUUUUCAAAUCCGAG3836
54790_1_15193−chr4: 105174856-105174876AAUAUUUUAGGGUUUUCAAA3837
54790_1_15201−chr4: 105174887-105174907CAUAAAGGGAAGGGAAACCC3838
54790_1_15202−chr4: 105174890-105174910AUCCAUAAAGGGAAGGGAAA3839
54790_1_15204−chr4: 105174891-105174911AAUCCAUAAAGGGAAGGGAA3840
54790_1_15207−chr4: 105174909-105174929CGAUUUUCCCCCGACUUGAA3841
54790_1_15211−chr4: 105174920-105174940GAUACACCUUUCGAUUUUCC3842
54790_1_15212−chr4: 105174921-105174941GGAUACACCUUUCGAUUUUC3843
54790_1_15213−chr4: 105174922-105174942GGGAUACACCUUUCGAUUUU3844
54790_1_15216−chr4: 105174923-105174943AGGGAUACACCUUUCGAUUU3845
54790_1_15223−chr4: 105174935-105174955AUAUAAAAGGAAAGGGAUAC3846
54790_1_15230−chr4: 105174977-105174997CGGGGGAUUGCACCUGUCCU3847
54790_1_15232−chr4: 105174981-105175001GAUCCGGGGGAUUGCACCUG3848
54790_1_15234−chr4: 105174986-105175006AAGGGGAUCCGGGGGAUUGC3849
54790_1_15240−chr4: 105174999-105175019GGUCAAAAGAGUCAAGGGGA3850
54790_1_15244−chr4: 105175035-105175055GAAACCACUUUGACAUGGGU3851
54790_1_15250−chr4: 105175052-105175072AUAUUAAACCAGAGGGAGAA3852
54790_1_15252−chr4: 105175065-105175085GUAAGACAUCGGAAUAUUAA3853
54790_1_15254−chr4: 105175091-105175111UAUCAUUUUCCACACCCUUU3854
54790_1_15255−chr4: 105175092-105175112CUAUCAUUUUCCACACCCUU3855
54790_1_15261−chr4: 105175097-105175117UUAUACUAUCAUUUUCCACA3856
54790_1_15263−chr4: 105175098-105175118AUUAUACUAUCAUUUUCCAC3857
54790_1_15266−chr4: 105175103-105175123AAAUCAUUAUACUAUCAUUU3858
54790_1_15267−chr4: 105175128-105175148AUUUUCUUUGACGACGUUUA3859
54790_1_15280−chr4: 105175177-105175197AUCGUACGGAAUAUUAAAAA3860
54790_1_15297−chr4: 105175282-105175302UAUCAAAAAAUAUUUCAAAG3861
54790_1_15321−chr4: 105175389-105175409ACUAUGAACCGUAAAGAGAA3862
54790_1_15324−chr4: 105175402-105175422ACAUGUGAUACGAACUAUGA3863
54790_1_15338−chr4: 105175473-105175493UUGAAGUUUCUAAAAAAGGA3864
54790_1_15390−chr4: 105175681-105175701ACCACAGACUGUAAUUAACC3865
54790_1_15392−chr4: 105175682-105175702AACCACAGACUGUAAUUAAC3866
54790_1_15394−chr4: 105175683-105175703AAACCACAGACUGUAAUUAA3867
54790_1_15396−chr4: 105175684-105175704CAAACCACAGACUGUAAUUA3868
54790_1_15401−chr4: 105175701-105175721UCGAGAGACCUCUUCAUCAA3869
54790_1_15407−chr4: 105175714-105175734AACCACAAGAAACUCGAGAG3870
54790_1_15415−chr4: 105175733-105175753AAACCCUGUAAAUAGGACGA3871
54790_1_15416−chr4: 105175750-105175770UAUACGGGUACUCAUCAAAA3872
54790_1_15418−chr4: 105175751-105175771UUAUACGGGUACUCAUCAAA3873
54790_1_15445−chr4: 105175821-105175841GAUAUCCACAAAAAAGGAAG3874
54790_1_15454−chr4: 105175837-105175857AUAAUAAAAACGAGGAGAUA3875
54790_1_15460−chr4: 105175877-105175897AGAAUAAACAUACCAAAUAC3876
54790_1_15463−chr4: 105175886-105175906UGAGAUGAGAGAAUAAACAU3877
54790_1_15472−chr4: 105175937-105175957CCAGGUCUUAGCAUGUGACG3878
54790_1_15479−chr4: 105175958-105175978AAGACUUCCUGUUAAAACGU3879
54790_1_15484−chr4: 105175972-105175992GAAAUAAAGAAUUGAAGACU3880
54790_1_15502−chr4: 105176032-105176052AAAAACGUUCCCACCAGGUG3881
54790_1_15505−chr4: 105176040-105176060AAUUUGUAAAAAACGUUCCC3882
54790_1_15506−chr4: 105176043-105176063UGAAAUUUGUAAAAAACGUU3883
54790_1_15507−chr4: 105176044-105176064UUGAAAUUUGUAAAAAACGU3884
54790_1_15524−chr4: 105176108-105176128GAUUAAAAUAAAAGGAAUAC3885
54790_1_15536−chr4: 105176146-105176166CAUAAAAGAAAUAGUUCAAC3886
54790_1_15537−chr4: 105176147-105176167ACAUAAAAGAAAUAGUUCAA3887
54790_1_15540−chr4: 105176148-105176168CACAUAAAAGAAAUAGUUCA3888
54790_1_15545−chr4: 105176177-105176197AAUUCAUACUACAUUUGACA3889
54790_1_15557−chr4: 105176221-105176241CAGAACAAGAACUAGAAUCG3890
54790_1_15561−chr4: 105176254-105176274CAUCCUUUGUUUCACCAUUC3891
54790_1_15565−chr4: 105176261-105176281UGAAGGUCAUCCUUUGUUUC3892
54790_1_15568−chr4: 105176272-105176292GUAAUCCAUCGUGAAGGUCA3893
54790_1_15579−chr4: 105176288-105176308AAGGAAACAGAAUAACGUAA3894
54790_1_15589−chr4: 105176334-105176354CUGUCAAACUAAAGAAGGAG3895
54790_1_15604−chr4: 105176392-105176412AAAAGAAAAAAGACUAGGAA3896
54790_1_15621−chr4: 105176473-105176493GACCAUAUGUCCUUUCACUA3897
54790_1_15625−chr4: 105176484-105176504GAACAAAUAACGACCAUAUG3898
54790_1_15629−chr4: 105176492-105176512UUUAAUGUGAACAAAUAACG3899
54790_1_15638−chr4: 105176532-105176552AGAACCCCACGAUUACAUUU3900
54790_1_15642−chr4: 105176547-105176567GUUUUCAUAAAGUAAAGAAC3901
54790_1_15643−chr4: 105176548-105176568UGUUUUCAUAAAGUAAAGAA3902
54790_1_15645−chr4: 105176549-105176569AUGUUUUCAUAAAGUAAAGA3903
54790_1_15666−chr4: 105176635-105176655GAGAAGUAAUAAAUCAAGUG3904
54790_1_15673−chr4: 105176692-105176712GACUUAGAUAUCUAGUUCAA3905
54790_1_15676−chr4: 105176693-105176713UGACUUAGAUAUCUAGUUCA3906
54790_1_15684−chr4: 105176722-105176742AUAGCACGACACAAAAAAUU3907
54790_1_15700−chr4: 105176806-105176826CAAGAGGAGUUUAUGACUCA3908
54790_1_15707−chr4: 105176853-105176873AAUAUCAUUCGAAAUUUCGG3909
54790_1_15724−chr4: 105176926-105176946CCGAGAAAUAAGAUAAGGUA3910
54790_1_15731−chr4: 105176947-105176967UAUAAAUGUACCCAAACAAA3911
54790_1_15733−chr4: 105176948-105176968AUAUAAAUGUACCCAAACAA3912
54790_1_15735−chr4: 105176957-105176977AGUAAACUAAUAUAAAUGUA3913
54790_1_15736−chr4: 105176958-105176978UAGUAAACUAAUAUAAAUGU3914
54790_1_15767−chr4: 105177087-105177107UAGACACAAAUGUGAGUUAA3915
54790_1_15775−chr4: 105177116-105177136AAGUUCAAUUAAAAACGUUU3916
54790_1_15776−chr4: 105177117-105177137UAAGUUCAAUUAAAAACGUU3917
54790_1_15787−chr4: 105177146-105177166AUCAAGACGUAAAAUGUAAA3918
54790_1_15794−chr4: 105177176-105177196AAAAAGGACACAAUAGAAGA3919
54790_1_15797−chr4: 105177177-105177197UAAAAAGGACACAAUAGAAG3920
54790_1_15799−chr4: 105177200-105177220GACGGUAUGGUUUCAGUAGA3921
54790_1_15806−chr4: 105177244-105177264AGGAAGUACAUAGCACGGAA3922
54790_1_15834−chr4: 105177347-105177367CGUUUAUUAAAAAGGUAGAC3923
54790_1_15871−chr4: 105177473-105177493GAAACCACUCAACAGACAAG3924
54790_1_15877−chr4: 105177490-105177510ACUGUGAACACAUAGAAGAA3925
54790_1_15893−chr4: 105177583-105177603GGUAAGAUUGUCCAUACAUC3926
54790_1_15895−chr4: 105177593-105177613GACUGAAGUCGGUAAGAUUG3927
54790_1_15901−chr4: 105177629-105177649AGGUGUAAGAGUGGUCGUGA3928
54790_1_15906−chr4: 105177662-105177682AAGAAUGGUCGUUACUUACU3929
54790_1_15921−chr4: 105177749-105177769CGCGAUAACGACUUAGUAUA3930
54790_1_15923−chr4: 105177750-105177770UCGCGAUAACGACUUAGUAU3931
54790_1_15930−chr4: 105177773-105177793UUCAAAAGUUCAGGUAUGGU3932
54790_1_15933−chr4: 105177800-105177820CACUCGAUGACACGGGCCGG3933
54790_1_15936−chr4: 105177805-105177825GUCCGCACUCGAUGACACGG3934
54790_1_15938−chr4: 105177824-105177844AGGGUUUCACGACGUUAAUG3935
54790_1_15939−chr4: 105177849-105177869GAGUUUACUAGGUGGACGGA3936
54790_1_15940−chr4: 105177850-105177870GGAGUUUACUAGGUGGACGG3937
54790_1_15948−chr4: 105177887-105177907UGGUACCCUAAAGUGGUCCG3938
54790_1_15949−chr4: 105177891-105177911AAAGUGGUACCCUAAAGUGG3939
54790_1_15952−chr4: 105177902-105177922AUCUCGACCCCAAAGUGGUA3940
54790_1_15954−chr4: 105177903-105177923CAUCUCGACCCCAAAGUGGU3941
54790_1_15961−chr4: 105177914-105177934AACAUAGAAAUCAUCUCGAC3942
54790_1_15962−chr4: 105177915-105177935AAACAUAGAAAUCAUCUCGA3943
54790_1_15964−chr4: 105177916-105177936AAAACAUAGAAAUCAUCUCG3944
54790_1_15968−chr4: 105177964-105177984AGGGAUCAUCGACUCUAAUG3945
54790_1_15971−chr4: 105178012-105178032GUGACGUUGGAGGCGGAGGA3946
54790_1_15972−chr4: 105178013-105178033AGUGACGUUGGAGGCGGAGG3947
54790_1_15974−chr4: 105178048-105178068AGUGAGUCCGACCUCACGUU3948
54790_1_15979−chr4: 105178058-105178078AAAACGAGACAGUGAGUCCG3949
54790_1_15981−chr4: 105178062-105178082CCUCAAAACGAGACAGUGAG3950
54790_1_15998−chr4: 105178083-105178103AAAACGAAAAAAAAAACUCU3951
54790_1_16016−chr4: 105178133-105178153UUACACACGUCCAAAAAUAC3952
54790_1_16018−chr4: 105178144-105178164UCGACAAUUUGUUACACACG3953
54790_1_16025−chr4: 105178178-105178198AGAACUAACGUGGGUUCAAA3954
54790_1_16029−chr4: 105178204-105178224AAAUAGGUGAGUUUAUAAUU3955
54790_1_16033−chr4: 105178238-105178258GACUUAUUAUAAGAAUGUAG3956
54790_1_16057−chr4: 105178339-105178359GUAUGUCAUAAAUCGGAAAA3957
54790_1_16063−chr4: 105178365-105178385AAAGGCCUUACAGUAUAUCA3958
54790_1_16070−chr4: 105178381-105178401GAGGUAUUAAAACCGAAAAG3959
54790_1_16076−chr4: 105178390-105178410AAAAUGACAGAGGUAUUAAA3960
54790_1_16081−chr4: 105178426-105178446ACGGAUAUGUAAGGAGGGAG3961
54790_1_16089−chr4: 105178497-105178517ACCUGUUUACAUAUUACUGU3962
54790_1_16093−chr4: 105178517-105178537CACCAAUGUAGGAUGCACAA3963
54790_1_16099−chr4: 105178536-105178556UGUAAUCCCAAGUGAUAACC3964
54790_1_16100−chr4: 105178539-105178559AAAUGUAAUCCCAAGUGAUA3965
54790_1_16101−chr4: 105178550-105178570UUUGGGGUAUCAAAUGUAAU3966
54790_1_16102−chr4: 105178551-105178571GUUUGGGGUAUCAAAUGUAA3967
54790_1_16112−chr4: 105178620-105178640UAGUUGUAGGGUAUGGUCUC3968
54790_1_16136−chr4: 105178759-105178779AAUAAUAUGAAAUUCAAAAU3969
54790_1_16138−chr4: 105178760-105178780UAAUAAUAUGAAAUUCAAAA3970
54790_1_16171−chr4: 105178880-105178900AAAUAUUUAAUGAGUCAGAG3971
54790_1_16192−chr4: 105179022-105179042GACUACCAAAAUAUUCACAA3972
54790_1_16194−chr4: 105179038-105179058ACUCAAGAGUACUCUAGACU3973
54790_1_16200−chr4: 105179063-105179083GGGUACGACAAGAGUAGUAU3974
54790_1_16202−chr4: 105179064-105179084GGGGUACGACAAGAGUAGUA3975
54790_1_16205−chr4: 105179094-105179114ACCUUCAUUAACCUAGUACC3976
54790_1_16206−chr4: 105179095-105179115CACCUUCAUUAACCUAGUAC3977
54790_1_16208−chr4: 105179096-105179116CCACCUUCAUUAACCUAGUA3978
54790_1_16210−chr4: 105179097-105179117UCCACCUUCAUUAACCUAGU3979
54790_1_16212−chr4: 105179104-105179124UCUCUGGUCCACCUUCAUUA3980
54790_1_16214−chr4: 105179114-105179134CACAGUUCCGUCUCUGGUCC3981
54790_1_16217−chr4: 105179117-105179137GUACACAGUUCCGUCUCUGG3982
54790_1_16219−chr4: 105179128-105179148AGGUAUUAUGGGUACACAGU3983
54790_1_16229−chr4: 105179199-105179219GUUUUAUCACACUAUACCAA3984
54790_1_16230−chr4: 105179204-105179224ACAUAGUUUUAUCACACUAU3985
54790_1_16238−chr4: 105179277-105179297AACCAGAAAUUGGAAAAUGG3986
54790_1_16241−chr4: 105179280-105179300CCUAACCAGAAAUUGGAAAA3987
54790_1_16246−chr4: 105179287-105179307UAUUUUUCCUAACCAGAAAU3988
54790_1_16252−chr4: 105179319-105179339AGGUUGUGGGUCAAUUAAGG3989
54790_1_16254−chr4: 105179322-105179342ACAAGGUUGUGGGUCAAUUA3990
54790_1_16260−chr4: 105179332-105179352UUCAUUGCAAACAAGGUUGU3991
54790_1_16262−chr4: 105179333-105179353CUUCAUUGCAAACAAGGUUG3992
54790_1_16265−chr4: 105179339-105179359UUGAUUCUUCAUUGCAAACA3993
54790_1_16274−chr4: 105179407-105179427AUUAUGCCCAUGGACACUCA3994
54790_1_16276−chr4: 105179417-105179437AGGCAACUGAAUUAUGCCCA3995
54790_1_16282−chr4: 105179437-105179457GUAUCAUUGGCAUUGAAUGA3996
54790_1_16288−chr4: 105179450-105179470UGUAGGCUUUGCAGUAUCAU3997
54790_1_16290−chr4: 105179467-105179487GGUACAUGAAUUUGCCUUGU3998
54790_1_16292−chr4: 105179488-105179508AAAGGAUGGAGUCUGUCUGU3999
54790_1_16296−chr4: 105179502-105179522GAAUAGUUUGAGAAAAAGGA4000
54790_1_16302−chr4: 105179506-105179526UCUUGAAUAGUUUGAGAAAA4001
54790_1_16320−chr4: 105179568-105179588UUUCAUUUUUUGAGGAUAGA4002
54790_1_16321−chr4: 105179576-105179596AGGAUAUUUUUCAUUUUUUG4003
54790_1_16326−chr4: 105179596-105179616CACUCAUUUCCCAAAUGAAG4004
54790_1_16335−chr4: 105179673-105179693AUUAUCAGAAAGCAGGUCAG4005
54790_1_16337−chr4: 105179680-105179700GUCAUGCAUUAUCAGAAAGC4006
54790_1_16345−chr4: 105179726-105179746AUACGGUCCAGUCCCAUGUG4007
54790_1_16346−chr4: 105179734-105179754AUCACCAAAUACGGUCCAGU4008
54790_1_16347−chr4: 105179735-105179755GAUCACCAAAUACGGUCCAG4009
54790_1_16350−chr4: 105179740-105179760UAUGAGAUCACCAAAUACGG4010
54790_1_16351−chr4: 105179751-105179771CUUUACUGAAUUAUGAGAUC4011
54790_1_16355−chr4: 105179804-105179824UGACAUCUAUCAGAAGGUCA4012
54790_1_16357−chr4: 105179805-105179825GUGACAUCUAUCAGAAGGUC4013
54790_1_16361−chr4: 105179832-105179852UAGGAAUGCAGCUGCUUUAG4014
54790_1_16366−chr4: 105179851-105179871AAACUUAAUCAUGCCUCACU4015
54790_1_16368−chr4: 105179876-105179896AUACUCCAGAACCUAAUAGU4016
54790_1_16370−chr4: 105179877-105179897AAUACUCCAGAACCUAAUAG4017
54790_1_16377−chr4: 105179910-105179930GCUAGAAAAACUUUCCUCUU4018
54790_1_16378−chr4: 105179911-105179931UGCUAGAAAAACUUUCCUCU4019
54790_1_16388−chr4: 105179981-105180001ACAAAUGAACAACCCUUAGU4020
54790_1_16390−chr4: 105180010-105180030GAAAAAAAACAGUGAAAGAA4021
54790_1_16393−chr4: 105180011-105180031AGAAAAAAAACAGUGAAAGA4022
54790_1_16399−chr4: 105180054-105180074CAACAGCCAGCUGACCAGAA4023
54790_1_16403−chr4: 105180078-105180098GAAAGUGUCAUUUCUAUGAU4024
54790_1_16411−chr4: 105180130-105180150AUGAGAAACAAAGUGAAGGC4025
54790_1_16415−chr4: 105180134-105180154UUGGAUGAGAAACAAAGUGA4026
54790_1_16423−chr4: 105180153-105180173GAAAGUUUUGUCAUUGAUUU4027
54790_1_16431−chr4: 105180194-105180214CCAAGUUGACUCAGGUUCAU4028
54790_1_16433−chr4: 105180202-105180222CCUUUAUGCCAAGUUGACUC4029
54790_1_16446−chr4: 105180273-105180293UCACUGAGCAAAGUGGAGUU4030
54790_1_16450−chr4: 105180280-105180300AAUGUUAUCACUGAGCAAAG4031
54790_1_16460−chr4: 105180324-105180344UGAGGAAGUAUUUUUAGACU4032
54790_1_16467−chr4: 105180342-105180362GACUGAGAUUUUGGAAUAUG4033
54790_1_16471−chr4: 105180351-105180371UGUAUUAAUGACUGAGAUUU4034
54790_1_16479−chr4: 105180400-105180420CUACAACAGCCGAGAAGCAC4035
54790_1_16497−chr4: 105180493-105180513AUAAACAUAAUUUUGCUUCC4036
54790_1_16511−chr4: 105180562-105180582AGAAUAUUUACGUUUUAGAA4037
54790_1_16516−chr4: 105180585-105180605GUUUGUGACCAUGGAGAUCA4038
54790_1_16520−chr4: 105180594-105180614UGAAAUACUGUUUGUGACCA4039
54790_1_16526−chr4: 105180634-105180654UUUUUUUUUUUUUGAUAAAA4040
54790_1_16531−chr4: 105180682-105180702CACGAAGACGUAGGGUCGGA4041
54790_1_16532−chr4: 105180683-105180703GCACGAAGACGUAGGGUCGG4042
54790_1_16535−chr4: 105180712-105180732UCCUCCACCUCCAACGUCAC4043
54790_1_16538−chr4: 105180723-105180743GCGAACUUGAGUCCUCCACC4044
54790_1_16539−chr4: 105180726-105180746UUAGCGAACUUGAGUCCUCC4045
54790_1_16542−chr4: 105180729-105180749CUCUUAGCGAACUUGAGUCC4046
54790_1_16544−chr4: 105180732-105180752GUCCUCUUAGCGAACUUGAG4047
54790_1_16549−chr4: 105180751-105180771CGAUGGGCCGUCCGACUCCG4048
54790_1_16552−chr4: 105180755-105180775AGAUCGAUGGGCCGUCCGAC4049
54790_1_16554−chr4: 105180761-105180781ACAUUAAGAUCGAUGGGCCG4050
54790_1_16555−chr4: 105180765-105180785ACGGACAUUAAGAUCGAUGG4051
54790_1_16557−chr4: 105180792-105180812UGUCUUAAUCGGUCCACACC4052
54790_1_16558−chr4: 105180795-105180815UUAUGUCUUAAUCGGUCCAC4053
54790_1_16559−chr4: 105180800-105180820GAUUUUUAUGUCUUAAUCGG4054
54790_1_16563−chr4: 105180848-105180868AGUCCUCAAGUUCUGGUCAG4055
54790_1_16565−chr4: 105180866-105180886ACCCACCUAGUGGACUCCAG4056
54790_1_16567−chr4: 105180871-105180891ACGCCACCCACCUAGUGGAC4057
54790_1_16571−chr4: 105180882-105180902GAAACCCUCCGACGCCACCC4058
54790_1_16574−chr4: 105180885-105180905CGUGAAACCCUCCGACGCCA4059
54790_1_16575−chr4: 105180886-105180906UCGUGAAACCCUCCGACGCC4060
54790_1_16577−chr4: 105180889-105180909AGGUCGUGAAACCCUCCGAC4061
54790_1_16578−chr4: 105180895-105180915ACAUUAAGGUCGUGAAACCC4062
54790_1_16580−chr4: 105180898-105180918CGGACAUUAAGGUCGUGAAA4063
54790_1_16581−chr4: 105180899-105180919GCGGACAUUAAGGUCGUGAA4064
54790_1_16587−chr4: 105180939-105180959GAGUUAAAAGAAAGAUAAAA4065
54790_1_16588−chr4: 105180940-105180960UGAGUUAAAAGAAAGAUAAA4066
54790_1_16595−chr4: 105180966-105180986CACAUGGAGGGAUAUAUUUG4067
54790_1_16599−chr4: 105180978-105180998GGAAGGCAACUUCACAUGGA4068
54790_1_16601−chr4: 105180979-105180999GGGAAGGCAACUUCACAUGG4069
54790_1_16604−chr4: 105180982-105181002UUAGGGAAGGCAACUUCACA4070
54790_1_16606−chr4: 105180995-105181015GGACAGUACAUAAUUAGGGA4071
54790_1_16608−chr4: 105180999-105181019ACUAGGACAGUACAUAAUUA4072
54790_1_16610−chr4: 105181000-105181020AACUAGGACAGUACAUAAUU4073
54790_1_16613−chr4: 105181016-105181036CAAGGAAUGAAGAUUAAACU4074
54790_1_16621−chr4: 105181034-105181054UGGUUUUAUAGAGGCAAACA4075
54790_1_16627−chr4: 105181043-105181063UUUUAAACUUGGUUUUAUAG4076
54790_1_16629−chr4: 105181054-105181074UCAGAGACUAUUUUUAAACU4077
54790_1_16643−chr4: 105181133-105181153UAGUAGAAACUUUGUUACAA4078
54790_1_16646−chr4: 105181165-105181185AUAUAGAUCGUAGCUGAGAA4079
54790_1_16649−chr4: 105181191-105181211UAUAACAAAAGACAUGGCCA4080
54790_1_16652−chr4: 105181197-105181217UGUGUGUAUAACAAAAGACA4081
54790_1_16658−chr4: 105181264-105181284AAAAGCAUAUUGUGACUAAA4082
54790_1_16661−chr4: 105181297-105181317AUCAAGAAAUUCCCAGGAAA4083
54790_1_16665−chr4: 105181303-105181323AAAAUCAUCAAGAAAUUCCC4084
54790_1_16674−chr4: 105181362-105181382GAAAAGCACUAUUUCUGCAG4085
54790_1_16679−chr4: 105181402-105181422UAUCACCAGCUCUUCUAAGA4086
54790_1_16682−chr4: 105181430-105181450AACCAAGAUAAAAGAAGAGU4087
54790_1_16694−chr4: 105181486-105181506UUGAUUGUCCUGUGUUAAAA4088
54790_1_16697−chr4: 105181487-105181507GUUGAUUGUCCUGUGUUAAA4089
54790_1_16701−chr4: 105181518-105181538UAUCUGAAUCUAAAGAAAGA4090
54790_1_16733−chr4: 105181612-105181632GGGGCAGGGGUUACAGAUGU4091
54790_1_16735−chr4: 105181625-105181645GUAAAAAAUAUUUGGGGCAG4092
54790_1_16736−chr4: 105181626-105181646AGUAAAAAAUAUUUGGGGCA4093
54790_1_16737−chr4: 105181627-105181647AAGUAAAAAAUAUUUGGGGC4094
54790_1_16740−chr4: 105181631-105181651GCAUAAGUAAAAAAUAUUUG4095
54790_1_16741−chr4: 105181632-105181652AGCAUAAGUAAAAAAUAUUU4096
54790_1_16743−chr4: 105181633-105181653UAGCAUAAGUAAAAAAUAUU4097
54790_1_16756−chr4: 105181718-105181738CAUCUUCGAUUUCCUAGAAG4098
54790_1_16758−chr4: 105181719-105181739ACAUCUUCGAUUUCCUAGAA4099
54790_1_16760−chr4: 105181720-105181740CACAUCUUCGAUUUCCUAGA4100
54790_1_16766−chr4: 105181748-105181768AACUCAUUAUCACAUUAAAC4101
54790_1_16783−chr4: 105181843-105181863CAAUCAUACUUAAGGUUGGA4102
54790_1_16784−chr4: 105181844-105181864UCAAUCAUACUUAAGGUUGG4103
54790_1_16787−chr4: 105181847-105181867AAUUCAAUCAUACUUAAGGU4104
54790_1_16789−chr4: 105181851-105181871UAUAAAUUCAAUCAUACUUA4105
54790_1_16800−chr4: 105181951-105181971UAUAUAAAAAUGAAAGUAUG4106
54790_1_16821−chr4: 105182073-105182093UAGCCAGAGAACAAAUGAUA4107
54790_1_16824−chr4: 105182074-105182094GUAGCCAGAGAACAAAUGAU4108
54790_1_16832−chr4: 105182099-105182119AAAAAUGUAACUAUUAACUU4109
54790_1_16838−chr4: 105182124-105182144UGCAAAUUACCAUUUGUCAC4110
54790_1_16848−chr4: 105182180-105182200UUUGCAUGAUUCUUAAAUAA4111
54790_1_16849−chr4: 105182181-105182201GUUUGCAUGAUUCUUAAAUA4112
54790_1_16852−chr4: 105182206-105182226CACCUGCUGCCUAUCAGCUC4113
54790_1_16858−chr4: 105182268-105182288AGCAGAAUUACUAGCUACCU4114
54790_1_16862−chr4: 105182292-105182312GAAGGAGCUAUAGUGGCUUA4115
54790_1_16863−chr4: 105182293-105182313GGAAGGAGCUAUAGUGGCUU4116
54790_1_16865−chr4: 105182299-105182319UAAUGGGGAAGGAGCUAUAG4117
54790_1_16867−chr4: 105182310-105182330GACCCAGGGAGUAAUGGGGA4118
54790_1_16870−chr4: 105182314-105182334GGUAGACCCAGGGAGUAAUG4119
54790_1_16872−chr4: 105182315-105182335GGGUAGACCCAGGGAGUAAU4120
54790_1_16874−chr4: 105182316-105182336UGGGUAGACCCAGGGAGUAA4121
54790_1_16876−chr4: 105182324-105182344CAGGAUGGUGGGUAGACCCA4122
54790_1_16878−chr4: 105182325-105182345GCAGGAUGGUGGGUAGACCC4123
54790_1_16885−chr4: 105182335-105182355UAUUCUAGCUGCAGGAUGGU4124
54790_1_16886−chr4: 105182336-105182356UUAUUCUAGCUGCAGGAUGG4125
54790_1_16888−chr4: 105182339-105182359UUAUUAUUCUAGCUGCAGGA4126
54790_1_16889−chr4: 105182343-105182363CCAUUUAUUAUUCUAGCUGC4127
54790_1_16891−chr4: 105182376-105182396GUGCUGGAGGAGGAUCCUAG4128
54790_1_16895−chr4: 105182386-105182406UUGAGACAUAGUGCUGGAGG4129
54790_1_16898−chr4: 105182389-105182409CCGUUGAGACAUAGUGCUGG4130
54790_1_16900−chr4: 105182392-105182412GGUCCGUUGAGACAUAGUGC4131
54790_1_16906−chr4: 105182410-105182430UAAAUUGUCGAGUAUACAGG4132
54790_1_16909−chr4: 105182448-105182468AGACGUCUCCCUUACCACAG4133
54790_1_16919−chr4: 105182513-105182533AAGUGUCUACUUUUAUCAUA4134
54790_1_16927−chr4: 105182572-105182592ACUCUGCAGUUAUGUUUACC4135
54790_1_16936−chr4: 105182598-105182618UUAAAGAUUUCAAAACGUAU4136
54790_1_16943−chr4: 105182639-105182659CUAAUCUAUUUCUAAUAGAA4137
54790_1_16949−chr4: 105182672-105182692UCAUUCUAAAAAUUGAAACA4138
54790_1_16967−chr4: 105182796-105182816AAUUCUAAUGCUUAAUGGGA4139
54790_1_16969−chr4: 105182800-105182820UAAAAAUUCUAAUGCUUAAU4140
54790_1_16971−chr4: 105182801-105182821AUAAAAAUUCUAAUGCUUAA4141
54790_1_16974−chr4: 105182831-105182851AUCAUGAAUAUAAACAUCAA4142
54790_1_16980−chr4: 105182874-105182894CAUAUGACCUAUAUGAGCUA4143
54790_1_16987−chr4: 105182908-105182928AGCCCAAAUAUCUUCAUCUA4144
54790_1_17002−chr4: 105182973-105182993UACAAUUUCUUCAAAAUGGA4145
54790_1_17004−chr4: 105182977-105182997ACCUUACAAUUUCUUCAAAA4146
54790_1_17013−chr4: 105183014-105183034AUUUUGGGGGGAUAAGUAUU4147
54790_1_17019−chr4: 105183026-105183046UUUAUUUUUCGUAUUUUGGG4148
54790_1_17021−chr4: 105183027-105183047UUUUAUUUUUCGUAUUUUGG4149
54790_1_17023−chr4: 105183028-105183048AUUUUAUUUUUCGUAUUUUG4150
54790_1_17024−chr4: 105183029-105183049GAUUUUAUUUUUCGUAUUUU4151
54790_1_17026−chr4: 105183030-105183050UGAUUUUAUUUUUCGUAUUU4152
54790_1_17041−chr4: 105183117-105183137CAGAUUGAGGAUCAAUAAAC4153
54790_1_17044−chr4: 105183130-105183150UUUAAAACAGCCACAGAUUG4154
54790_1_17051−chr4: 105183184-105183204GAGUAAUGAGUCUACUACCA4155
54790_1_17056−chr4: 105183206-105183226AAAUGAUGUAAUGGUUUCUG4156
54790_1_17059−chr4: 105183207-105183227AAAAUGAUGUAAUGGUUUCU4157
54790_1_17060−chr4: 105183208-105183228CAAAAUGAUGUAAUGGUUUC4158
54790_1_17065−chr4: 105183215-105183235AAUAUUACAAAAUGAUGUAA4159
54790_1_17086−chr4: 105183346-105183366UGUGAUAUUAAGUUUAUAAA4160
54790_1_17093−chr4: 105183389-105183409CACAAGCAAAAUUAUAUUAA4161
54790_1_17097−chr4: 105183420-105183440AAAGAGUUAUUGAAAUGAAU4162
54790_1_17104−chr4: 105183445-105183465UUGAGAUAAAAAAUAUAUAU4163
54790_1_17120−chr4: 105183501-105183521AGACAAGGUUGGGUCGAAAU4164
54790_1_17127−chr4: 105183559-105183579GGCUAGUGAAUCCCUUUGAC4165
54790_1_17131−chr4: 105183568-105183588CUAGAACUCGGCUAGUGAAU4166
54790_1_17134−chr4: 105183569-105183589ACUAGAACUCGGCUAGUGAA4167
54790_1_17141−chr4: 105183625-105183645UGUUUCAUAUUUAAUUAGAA4168
54790_1_17142−chr4: 105183626-105183646UUGUUUCAUAUUUAAUUAGA4169
54790_1_17147−chr4: 105183662-105183682CACAGGCAAACUAAGGGGGU4170
54790_1_17148−chr4: 105183666-105183686AACCCACAGGCAAACUAAGG4171
54790_1_17149−chr4: 105183667-105183687AAACCCACAGGCAAACUAAG4172
54790_1_17151−chr4: 105183668-105183688UAAACCCACAGGCAAACUAA4173
54790_1_17153−chr4: 105183669-105183689AUAAACCCACAGGCAAACUA4174
54790_1_17156−chr4: 105183679-105183699UGUAACUUCCAUAAACCCAC4175
54790_1_17165−chr4: 105183731-105183751CAAUAAUUCUAUUGGGAGCU4176
54790_1_17167−chr4: 105183738-105183758UACAGGGCAAUAAUUCUAUU4177
54790_1_17168−chr4: 105183739-105183759CUACAGGGCAAUAAUUCUAU4178
54790_1_17174−chr4: 105183754-105183774UAUUUGCGCGGCUGACUACA4179
54790_1_17175−chr4: 105183755-105183775GUAUUUGCGCGGCUGACUAC4180
54790_1_17179−chr4: 105183766-105183786UAUUUGUGAUUGUAUUUGCG4181
54790_1_17187−chr4: 105183789-105183809UUCUUCACACAAGGAACUUC4182
54790_1_17190−chr4: 105183798-105183818AUUUUCUUUUUCUUCACACA4183
54790_1_17200−chr4: 105183853-105183873GGGAAGAAAGGGGCAAAGAA4184
54790_1_17202−chr4: 105183863-105183883GGAGUGAAAGGGGAAGAAAG4185
54790_1_17203−chr4: 105183864-105183884AGGAGUGAAAGGGGAAGAAA4186
54790_1_17204−chr4: 105183865-105183885AAGGAGUGAAAGGGGAAGAA4187
54790_1_17208−chr4: 105183873-105183893GGAGAAGAAAGGAGUGAAAG4188
54790_1_17210−chr4: 105183874-105183894AGGAGAAGAAAGGAGUGAAA4189
54790_1_17213−chr4: 105183875-105183895UAGGAGAAGAAAGGAGUGAA4190
54790_1_17218−chr4: 105183884-105183904CAAGUAGUAUAGGAGAAGAA4191
54790_1_17225−chr4: 105183894-105183914CUAGAAAUUUCAAGUAGUAU4192
54790_1_17234−chr4: 105183934-105183954ACUUACCAUUCCUAACAUCC4193
54790_1_17246−chr4: 105184003-105184023UGAAAAGCCUCUUAAGGGUA4194
54790_1_17248−chr4: 105184008-105184028AACUUUGAAAAGCCUCUUAA4195
54790_1_17249−chr4: 105184009-105184029UAACUUUGAAAAGCCUCUUA4196
54790_1_17252−chr4: 105184047-105184067GUCAGAGACUGGGCCAAUGA4197
54790_1_17256−chr4: 105184057-105184077GACCUCACUGGUCAGAGACU4198
54790_1_17257−chr4: 105184058-105184078UGACCUCACUGGUCAGAGAC4199
54790_1_17260−chr4: 105184069-105184089UGGCUAAUACUUGACCUCAC4200
54790_1_17265−chr4: 105184089-105184109UUUUCACGACAUUCUGACAC4201
54790_1_17279−chr4: 105184189-105184209GAUAUUUUUAAAAACCAAGA4202
54790_1_17289−chr4: 105184231-105184251AAAAUAAAAAGAAGUUAUGA4203
54790_1_17291−chr4: 105184232-105184252GAAAAUAAAAAGAAGUUAUG4204
54790_1_17303−chr4: 105184294-105184314GGUACAGGUAUAAAUUCACA4205
54790_1_17304−chr4: 105184309-105184329CACUGGAACAUGAGAGGUAC4206
54790_1_17305−chr4: 105184315-105184335ACCAAACACUGGAACAUGAG4207
54790_1_17312−chr4: 105184326-105184346AUUAUUUAAGAACCAAACAC4208
54790_1_17325−chr4: 105184408-105184428AUAACUACGAUAGCCAAACA4209
54790_1_17330−chr4: 105184455-105184475AAACAAGCAUACACCAUAUG4210
54790_1_17340−chr4: 105184529-105184549UCCUCCUAACAUAGACAAAG4211
54790_1_17356−chr4: 105184641-105184661UGUCAGCUACUUGGCAGUGA4212
54790_1_17359−chr4: 105184650-105184670AUUUCAGAAUGUCAGCUACU4213
54790_1_17362−chr4: 105184680-105184700CCAACUGUACAGUGCCUAAA4214
54790_1_17365−chr4: 105184681-105184701UCCAACUGUACAGUGCCUAA4215
54790_1_17373−chr4: 105184797-105184817AGCACGUUACUCACCUCAGC4216
54790_1_17378−chr4: 105184832-105184852AGGUUUAAAUGGGAUGAGAC4217
54790_1_17383−chr4: 105184842-105184862GUUCUCCUCCAGGUUUAAAU4218
54790_1_17385−chr4: 105184843-105184863GGUUCUCCUCCAGGUUUAAA4219
54790_1_17389−chr4: 105184852-105184872GCUUGAUGUGGUUCUCCUCC4220
54790_1_17392−chr4: 105184864-105184884GGCUGCUUCUGUGCUUGAUG4221
54790_1_17397−chr4: 105184885-105184905UUCCUGUUGAAAUGCUGCUU4222
54790_1_17406−chr4: 105184943-105184963GUGAUAUUAGUACACCUUCA4223
54790_1_17418−chr4: 105185007-105185027AACACUUCCGUUACAAAAAA4224
54790_1_17419−chr4: 105185008-105185028AAACACUUCCGUUACAAAAA4225
54790_1_17434−chr4: 105185084-105185104AUAUAAGAAUCCUCCAUUUG4226
54790_1_17435−chr4: 105185085-105185105UAUAUAAGAAUCCUCCAUUU4227
54790_1_17437−chr4: 105185086-105185106UUAUAUAAGAAUCCUCCAUU4228
54790_1_17441−chr4: 105185113-105185133UGAAUAUAUCAUUACAAGCU4229
54790_1_17448−chr4: 105185184-105185204AAGUUUUCGUUCAAAAAUGA4230
54790_1_17461−chr4: 105185242-105185262AAACAUUUCAUUUUGGGGAA4231
54790_1_17464−chr4: 105185247-105185267CAGUGAAACAUUUCAUUUUG4232
54790_1_17465−chr4: 105185248-105185268UCAGUGAAACAUUUCAUUUU4233
54790_1_17467−chr4: 105185249-105185269UUCAGUGAAACAUUUCAUUU4234
54790_1_17473−chr4: 105185275-105185295CAUGGCCUCCACAAGCUUGU4235
54790_1_17478−chr4: 105185293-105185313CUCUUAUUCAACAUGCUUCA4236
54790_1_17483−chr4: 105185331-105185351CACACCCUUUGUGGGUGGCA4237
54790_1_17484−chr4: 105185332-105185352GCACACCCUUUGUGGGUGGC4238
54790_1_17488−chr4: 105185336-105185356CUUAGCACACCCUUUGUGGG4239
54790_1_17490−chr4: 105185339-105185359UACCUUAGCACACCCUUUGU4240
54790_1_17491−chr4: 105185340-105185360UUACCUUAGCACACCCUUUG4241
54790_1_17500−chr4: 105185401-105185421AAUAGCUAAAAUUUAUUGAA4242
54790_1_17515−chr4: 105185482-105185502CCAGUCACUGUGUUUUAGAA4243
54790_1_17518−chr4: 105185503-105185523GUCCGUACUCGGUGACGCGG4244
54790_1_17520−chr4: 105185522-105185542AGGCUUUCACGACCCUAAUG4245
54790_1_17521−chr4: 105185530-105185550GGAGCCGGAGGCUUUCACGA4246
54790_1_17522−chr4: 105185531-105185551UGGAGCCGGAGGCUUUCACG4247
54790_1_17526−chr4: 105185547-105185567UGGAGCACUAGGCGUAUGGA4248
54790_1_17530−chr4: 105185583-105185603AAAGUGGCACAAUCGGUCCU4249
54790_1_17531−chr4: 105185587-105185607CCCUAAAGUGGCACAAUCGG4250
54790_1_17541−chr4: 105185607-105185627AAACAUAAAAAUCAUCUCUG4251
54790_1_17542−chr4: 105185608-105185628AAAACAUAAAAAUCAUCUCU4252
54790_1_17547−chr4: 105185636-105185656GUCCGCGUACGGGGGUGCGG4253
54790_1_17548−chr4: 105185655-105185675AGGACUCAUCGACCCUAAUG4254
54790_1_17549−chr4: 105185663-105185683GGAGUCGGAGGACUCAUCGA4255
54790_1_17550−chr4: 105185664-105185684CGGAGUCGGAGGACUCAUCG4256
54790_1_17556−chr4: 105185703-105185723GUGACGUUCGAGGCGGAGGG4257
54790_1_17558−chr4: 105185728-105185748CCUCACGUCACCACGCUAGA4258
54790_1_17559−chr4: 105185739-105185759AUCGGGUCCGACCUCACGUC4259
54790_1_17562−chr4: 105185749-105185769AGAACGAGACAUCGGGUCCG4260
54790_1_17564−chr4: 105185753-105185773UCUCAGAACGAGACAUCGGG4261
54790_1_17613−chr4: 105185968-105185988AAGGUUUCACGACCCUAAUG4262
54790_1_17614−chr4: 105185976-105185996GCAGUUGGAAGGUUUCACGA4263
54790_1_17616−chr4: 105185977-105185997CGCAGUUGGAAGGUUUCACG4264
54790_1_17619−chr4: 105186031-105186051AGAGUGAUACAACGGGUCCG4265
54790_1_17620−chr4: 105186035-105186055CUCCAGAGUGAUACAACGGG4266
54790_1_17632−chr4: 105186054-105186074CAAAUAAAAAACAUCUCUAC4267
54790_1_17636−chr4: 105186106-105186126AGGGUUCACCGAUCCUGAUG4268
54790_1_17638−chr4: 105186114-105186134AGAGUCAGAGGGUUCACCGA4269
54790_1_17640−chr4: 105186119-105186139AAGGUAGAGUCAGAGGGUUC4270
54790_1_17641−chr4: 105186179-105186199GUUCACGUCACCGUGCUAGA4271
54790_1_17642−chr4: 105186190-105186210AGUGGGUCCGAGUUCACGUC4272
54790_1_17644−chr4: 105186204-105186224UCCCAGAACGAGACAGUGGG4273
54790_1_17657−chr4: 105186223-105186243AACAAACAAAAGAACUCUGU4274
54790_1_17658−chr4: 105186224-105186244AAACAAACAAAAGAACUCUG4275
54790_1_17674−chr4: 105186324-105186344UAAGAUAAGGGCCAUGAAGG4276
54790_1_17675−chr4: 105186325-105186345UUAAGAUAAGGGCCAUGAAG4277
54790_1_17676−chr4: 105186326-105186346GUUAAGAUAAGGGCCAUGAA4278
54790_1_17679−chr4: 105186327-105186347GGUUAAGAUAAGGGCCAUGA4279
54790_1_17682−chr4: 105186336-105186356GAAGACAGAGGUUAAGAUAA4280
54790_1_17683−chr4: 105186337-105186357UGAAGACAGAGGUUAAGAUA4281
54790_1_17685−chr4: 105186348-105186368AAGGGUAGUGCUGAAGACAG4282
54790_1_17688−chr4: 105186366-105186386AAACGGAACAAACAUAUGAA4283
54790_1_17689−chr4: 105186367-105186387AAAACGGAACAAACAUAUGA4284
54790_1_17694−chr4: 105186383-105186403AAAUCACUUAGAAGAUAAAA4285
54790_1_17711−chr4: 105186518-105186538CGUGGUGACGUGAGGUCGGA4286
54790_1_17712−chr4: 105186519-105186539GCGUGGUGACGUGAGGUCGG4287
54790_1_17716−chr4: 105186559-105186579CUUAGCGGAGGUCCUCCGCC4288
54790_1_17717−chr4: 105186562-105186582CCUCUUAGCGGAGGUCCUCC4289
54790_1_17720−chr4: 105186565-105186585CGCCCUCUUAGCGGAGGUCC4290
54790_1_17721−chr4: 105186568-105186588CUCCGCCCUCUUAGCGGAGG4291
54790_1_17725−chr4: 105186583-105186603CGAUGACCCCUCCGACUCCG4292
54790_1_17728−chr4: 105186584-105186604UCGAUGACCCCUCCGACUCC4293
54790_1_17730−chr4: 105186587-105186607GGGUCGAUGACCCCUCCGAC4294
54790_1_17732−chr4: 105186593-105186613ACAUCAGGGUCGAUGACCCC4295
54790_1_17733−chr4: 105186596-105186616CGGACAUCAGGGUCGAUGAC4296
54790_1_17735−chr4: 105186597-105186617UCGGACAUCAGGGUCGAUGA4297
54790_1_17737−chr4: 105186598-105186618UUCGGACAUCAGGGUCGAUG4298
54790_1_17741−chr4: 105186624-105186644AUUUUUAAUAGGUCCGUACC4299
54790_1_17742−chr4: 105186627-105186647UAUAUUUUUAAUAGGUCCGU4300
54790_1_17743−chr4: 105186632-105186652AUUUUUAUAUUUUUAAUAGG4301
54790_1_17749−chr4: 105186699-105186719ACCCACCUAGUGAACUCCAG4302
54790_1_17752−chr4: 105186704-105186724GUUCCACCCACCUAGUGAAC4303
54790_1_17756−chr4: 105186715-105186735GAAACCCUCCGGUUCCACCC4304
54790_1_17758−chr4: 105186718-105186738CGUGAAACCCUCCGGUUCCA4305
54790_1_17759−chr4: 105186719-105186739UCGUGAAACCCUCCGGUUCC4306
54790_1_17761−chr4: 105186722-105186742GGGUCGUGAAACCCUCCGGU4307
54790_1_17762−chr4: 105186728-105186748ACGUUAGGGUCGUGAAACCC4308
54790_1_17763−chr4: 105186731-105186751CGGACGUUAGGGUCGUGAAA4309
54790_1_17765−chr4: 105186732-105186752ACGGACGUUAGGGUCGUGAA4310
54790_1_17770−chr4: 105186759-105186779AUCAUGAACGGUCCGGCGCC4311
54790_1_17772−chr4: 105186762-105186782UGGAUCAUGAACGGUCCGGC4312
54790_1_17773−chr4: 105186768-105186788CUAUUUUGGAUCAUGAACGG4313
54790_1_17776−chr4: 105186782-105186802GAAGCUUAAUGAUGCUAUUU4314
54790_1_17786−chr4: 105186827-105186847UAAAUACAGUGAUGACUCAC4315
54790_1_17795−chr4: 105186893-105186913UCCUCAGUAGCCAAUAAUUC4316
54790_1_17801−chr4: 105186957-105186977CAGUCCCCUUUAGUAAAAAG4317
54790_1_17809−chr4: 105187014-105187034AUCAAGCUGGCAAACUAUCA4318
54790_1_17814−chr4: 105187027-105187047UGGUUGACUGGGAAUCAAGC4319
54790_1_17816−chr4: 105187038-105187058CAGCAGUUAUCUGGUUGACU4320
54790_1_17817−chr4: 105187039-105187059CCAGCAGUUAUCUGGUUGAC4321
54790_1_17820−chr4: 105187047-105187067UGUCACUACCAGCAGUUAUC4322
54790_1_17823−chr4: 105187077-105187097CACAAGAUUGGGAGUCCUGG4323
54790_1_17825−chr4: 105187080-105187100UGGCACAAGAUUGGGAGUCC4324
54790_1_17829−chr4: 105187088-105187108CUCUGAGCUGGCACAAGAUU4325
54790_1_17832−chr4: 105187089-105187109UCUCUGAGCUGGCACAAGAU4326
54790_1_17835−chr4: 105187100-105187120GGGGAUUUCCCUCUCUGAGC4327
54790_1_17839−chr4: 105187119-105187139AUGGUGUGAGCAGUUCUAGG4328
54790_1_17840−chr4: 105187120-105187140AAUGGUGUGAGCAGUUCUAG4329
54790_1_17842−chr4: 105187121-105187141GAAUGGUGUGAGCAGUUCUA4330
54790_1_17845−chr4: 105187122-105187142GGAAUGGUGUGAGCAGUUCU4331
54790_1_17850−chr4: 105187138-105187158GGUGCUUGUGGUUCUUGGAA4332
54790_1_17851−chr4: 105187143-105187163AAGGUGGUGCUUGUGGUUCU4333
54790_1_17856−chr4: 105187150-105187170CUAUACCAAGGUGGUGCUUG4334
54790_1_17859−chr4: 105187159-105187179CAUUUUUAACUAUACCAAGG4335
54790_1_17861−chr4: 105187162-105187182UCACAUUUUUAACUAUACCA4336
54790_1_17869−chr4: 105187187-105187207GUUUUUAUCAGAAUUUGAGU4337
54790_1_17891−chr4: 105187296-105187316CCAAAUACUGAGGAAGGCAG4338
54790_1_17894−chr4: 105187302-105187322GACAAACCAAAUACUGAGGA4339
54790_1_17897−chr4: 105187306-105187326AACUGACAAACCAAAUACUG4340
54790_1_17908−chr4: 105187371-105187391ACAUUAUUAAGAUUAGAAGA4341
54790_1_17909−chr4: 105187372-105187392AACAUUAUUAAGAUUAGAAG4342
54790_1_17927−chr4: 105187431-105187451AGGUCAGGGUUGGAGUCAAU4343
54790_1_17928−chr4: 105187441-105187461GAAGUACAGGAGGUCAGGGU4344
54790_1_17931−chr4: 105187445-105187465AGGUGAAGUACAGGAGGUCA4345
54790_1_17932−chr4: 105187446-105187466CAGGUGAAGUACAGGAGGUC4346
54790_1_17935−chr4: 105187451-105187471UCAGGCAGGUGAAGUACAGG4347
54790_1_17937−chr4: 105187454-105187474UCAUCAGGCAGGUGAAGUAC4348
54790_1_17941−chr4: 105187465-105187485CAAAUAAAUAUUCAUCAGGC4349
54790_1_17943−chr4: 105187469-105187489AUUCCAAAUAAAUAUUCAUC4350
54790_1_17951−chr4: 105187541-105187561AUAAAUAGAUAAUUCUAGAA4351
54790_1_17965−chr4: 105187593-105187613AGUGAUAAAGCUUUUGAGUU4352
54790_1_17978−chr4: 105187663-105187683AUUACUGAUAAAGAAAUGAA4353
54790_1_17985−chr4: 105187720-105187740CAAUAGUUGGAAUGAGAGGG4354
54790_1_17986−chr4: 105187723-105187743AAGCAAUAGUUGGAAUGAGA4355
54790_1_17987−chr4: 105187724-105187744UAAGCAAUAGUUGGAAUGAG4356
54790_1_17992−chr4: 105187733-105187753ACUCAAGUAUAAGCAAUAGU4357
54790_1_17998−chr4: 105187767-105187787AAUAAUCAUAUGCAAGAUAU4358
54790_1_18001−chr4: 105187797-105187817ACACUUCACCAUGAAGAUUU4359
54790_1_18004−chr4: 105187810-105187830GGUAGGGUCACUCACACUUC4360
54790_1_18022−chr4: 105187890-105187910UAAGGUGAUCGUUACACAGU4361
54790_1_18024−chr4: 105187891-105187911GUAAGGUGAUCGUUACACAG4362
54790_1_18029−chr4: 105187927-105187947ACGGUUUGACAAAACGUUUC4363
54790_1_18037−chr4: 105187978-105187998UCGCUUUGAUGACCCAGAAU4364
54790_1_18038−chr4: 105187986-105188006AGGGAUUCUCGCUUUGAUGA4365
54790_1_18039−chr4: 105187987-105188007UAGGGAUUCUCGCUUUGAUG4366
54790_1_18049−chr4: 105188011-105188031CAAAAGUUAAGAGAACUCUC4367
54790_1_18059−chr4: 105188039-105188059UACAAAUAUUCAAAAACAUA4368
54790_1_18060−chr4: 105188040-105188060UUACAAAUAUUCAAAAACAU4369
54790_1_18063−chr4: 105188069-105188089CUUAUUACGACGUUGUUUGU4370
54790_1_18072−chr4: 105188099-105188119AAACCCAACGAAGAUGGAAA4371
54790_1_18074−chr4: 105188116-105188136AGUAGGUAGACAUCCGUAAA4372
54790_1_18075−chr4: 105188117-105188137AAGUAGGUAGACAUCCGUAA4373
54790_1_18079−chr4: 105188124-105188144AAUAGGUAAGUAGGUAGACA4374
54790_1_18090−chr4: 105188186-105188206GUCUUAAAAGAAGGAGAAAU4375
54790_1_18108−chr4: 105188262-105188282UUAUAAAAAGAAACACACUA4376
54790_1_18111−chr4: 105188291-105188311AAGAUUCAUGGAGUACAUUC4377
54790_1_18120−chr4: 105188353-105188373AACGAGGAGGAGGGUCGGGG4378
54790_1_18138−chr4: 105188483-105188503AUAAAUUCAUAUGAUAAGAC4379
54790_1_18155−chr4: 105188569-105188589GGAGUAUUUAUUACGAAGAA4380
54790_1_18165−chr4: 105188608-105188628CGAUAGUUACUACUUGAAAA4381
54790_1_18166−chr4: 105188609-105188629UCGAUAGUUACUACUUGAAA4382
54790_1_18189−chr4: 105188715-105188735GUGAAUCACAUUACAAAAAU4383
54790_1_18196−chr4: 105188745-105188765UUUUAAACCGGAAAAUGCAG4384
54790_1_18198−chr4: 105188759-105188779UAUAUUUUGGUAUGUUUUAA4385
54790_1_18211−chr4: 105188808-105188828UUAGUUGAAAGUCAGAAAUA4386
54790_1_18212−chr4: 105188809-105188829AUUAGUUGAAAGUCAGAAAU4387
54790_1_18220−chr4: 105188839-105188859AAGUAAGGAGGGGGCCCGGA4388
54790_1_18221−chr4: 105188845-105188865AAAAGUAAGUAAGGAGGGGG4389
54790_1_18222−chr4: 105188846-105188866CAAAAGUAAGUAAGGAGGGG4390
54790_1_18225−chr4: 105188874-105188894GUUUUUUGGGUCAUGGGUAA4391
54790_1_18239−chr4: 105188985-105189005ACAUUUCAUAUACUCAGUCA4392
54790_1_18240−chr4: 105188986-105189006AACAUUUCAUAUACUCAGUC4393
54790_1_18251−chr4: 105189047-105189067GCCAUACGUUAAAAUUUAAG4394
54790_1_18252−chr4: 105189048-105189068AGCCAUACGUUAAAAUUUAA4395
54790_1_18253−chr4: 105189049-105189069AAGCCAUACGUUAAAAUUUA4396
54790_1_18260−chr4: 105189080-105189100ACGUUGCUUCUUUAGAAACA4397
54790_1_18262−chr4: 105189105-105189125UCUUUAUCAUUCGACUCUGA4398
54790_1_18263−chr4: 105189106-105189126AUCUUUAUCAUUCGACUCUG4399
54790_1_18278−chr4: 105189159-105189179UAAAAUGUCUCAUUCUUCCC4400
54790_1_18281−chr4: 105189162-105189182GGGUAAAAUGUCUCAUUCUU4401
54790_1_18283−chr4: 105189163-105189183AGGGUAAAAUGUCUCAUUCU4402
54790_1_18296−chr4: 105189225-105189245UAAAUUGUGAGUUUUUUUAG4403
54790_1_18302−chr4: 105189291-105189311GCUCAGGUUCCCGGGGUUGA4404
54790_1_18303−chr4: 105189298-105189318AGUUGAAGCUCAGGUUCCCG4405
54790_1_18304−chr4: 105189299-105189319CAGUUGAAGCUCAGGUUCCC4406
54790_1_18305−chr4: 105189300-105189320GCAGUUGAAGCUCAGGUUCC4407
54790_1_18308−chr4: 105189307-105189327AUCAGAAGCAGUUGAAGCUC4408
54790_1_18313−chr4: 105189336-105189356GAAUAUCCUGAAAUAGUAUC4409
54790_1_18319−chr4: 105189358-105189378UGAAUAUAUGGAAACAGUAU4410
54790_1_18322−chr4: 105189370-105189390GGUCCAUUGUCCUGAAUAUA4411
54790_1_18329−chr4: 105189391-105189411GAUAAAAUGGCUAAAGGAGU4412
54790_1_18331−chr4: 105189397-105189417AGUUUUGAUAAAAUGGCUAA4413
54790_1_18333−chr4: 105189404-105189424UCUAAAGAGUUUUGAUAAAA4414
54790_1_18342−chr4: 105189448-105189468AAAGGAGCACAAGAAGACUU4415
54790_1_18347−chr4: 105189466-105189486UGACUGAAGAGUGUCUACAA4416
54790_1_18353−chr4: 105189507-105189527AUACAGCUGCAGCAAAUUGG4417
54790_1_18356−chr4: 105189510-105189530CAGAUACAGCUGCAGCAAAU4418
54790_1_18363−chr4: 105189535-105189555GGGGAGAAAGCGUUGUUUUG4419
54790_1_18367−chr4: 105189554-105189574GCAGAGAGAAAAGAGGAAUG4420
54790_1_18368−chr4: 105189555-105189575GGCAGAGAGAAAAGAGGAAU4421
54790_1_18372−chr4: 105189556-105189576GGGCAGAGAGAAAAGAGGAA4422
54790_1_18375−chr4: 105189561-105189581UCCAAGGGCAGAGAGAAAAG4423
54790_1_18381−chr4: 105189576-105189596AGAAGUCCACAGAGUUCCAA4424
54790_1_18382−chr4: 105189577-105189597GAGAAGUCCACAGAGUUCCA4425
54790_1_18390−chr4: 105189612-105189632AUGCACUGAUAAAAGGGAGU4426
54790_1_18392−chr4: 105189618-105189638GAUGACAUGCACUGAUAAAA4427
54790_1_18393−chr4: 105189619-105189639AGAUGACAUGCACUGAUAAA4428
54790_1_18398−chr4: 105189642-105189662UAUUGGGUGCUACAAAUAAG4429
54790_1_18400−chr4: 105189658-105189678AAAGAUGUAGUAAAAAUAUU4430
54790_1_18402−chr4: 105189659-105189679CAAAGAUGUAGUAAAAAUAU4431
54790_1_18405−chr4: 105189683-105189703UAACCCAAGUAAGACUUAAU4432
54790_1_18410−chr4: 105189737-105189757CUGACCUGUAUAUCUUUAAA4433
54790_1_18417−chr4: 105189754-105189774AAAUUAAAUCGACCUCUCUG4434
54790_1_18421−chr4: 105189763-105189783GAGUUCCCAAAAUUAAAUCG4435
54790_1_18423−chr4: 105189778-105189798GUACACCAGAGACACGAGUU4436
54790_1_18425−chr4: 105189779-105189799UGUACACCAGAGACACGAGU4437
54790_1_18427−chr4: 105189794-105189814UCCAUUUUGUAAUAUUGUAC4438
54790_1_18428−chr4: 105189814-105189834GUACGAUUCACGAUACCUUU4439
54790_1_18429−chr4: 105189820-105189840UCCAUUGUACGAUUCACGAU4440
54790_1_18434−chr4: 105189840-105189860UAAGUCAUAUACGGUACAGU4441
54790_1_18437−chr4: 105189894-105189914UCCCUGUACUUCAUGAGAUG4442
54790_1_18442−chr4: 105189933-105189953CCACUGACAUUCUACUUCAG4443
54790_1_18448−chr4: 105189954-105189974UUCUCCUUUGAAAUAAGAGG4444
54790_1_18453−chr4: 105189971-105189991AAGACUGAACAACUCGAUUC4445
54790_1_18462−chr4: 105190008-105190028UAGUGGAUCCAUUCUUCAAC4446
54790_1_18468−chr4: 105190021-105190041CCGAAUGUUCUCAUAGUGGA4447
54790_1_18472−chr4: 105190042-105190062GAAUCGUCACCAAGUGUCAC4448
54790_1_18475−chr4: 105190054-105190074ACUUCAUCUGUUGAAUCGUC4449
54790_1_18479−chr4: 105190085-105190105CAAUGAGGCUUAAGAGCCAG4450
54790_1_18482−chr4: 105190100-105190120CUUCACCGCAAUAAUCAAUG4451
54790_1_18502−chr4: 105190241-105190261UGGAUAUUUCCAUUACAGUG4452
54790_1_18507−chr4: 105190261-105190281AGGUUUUGGAUACCUAUAAU4453
54790_1_18510−chr4: 105190275-105190295AUAAAGAGUUUAAAAGGUUU4454
54790_1_18512−chr4: 105190281-105190301CCUGAUAUAAAGAGUUUAAA4455
54790_1_18519−chr4: 105190312-105190332UAAGUUAGCAAAAAGGAACA4456
54790_1_18520−chr4: 105190313-105190333UUAAGUUAGCAAAAAGGAAC4457
54790_1_18525−chr4: 105190319-105190339ACAUUUUUAAGUUAGCAAAA4458
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54790_2_251+chr4: 105191722-105191742AGUUGAACUCCCAUGAUUCC4499
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54790_2_300+chr4: 105191934-105191954CUCUCAUGCUGGAAAAUCUU4507
54790_2_327+chr4: 105192067-105192087CUGAGAGCGCAUUUUUAAGA4508
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54790_2_345+chr4: 105192135-105192155UCUUCUUGAACGUUAAGCCU4510
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54790_2_437+chr4: 105192529-105192549GUAAGUUCUCAAUUUUAUAU4525
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54790_2_475+chr4: 105192651-105192671CACUCUUCUAGGAACUAGAG4528
54790_2_479+chr4: 105192668-105192688GAGUGGCAUUAAUGAGUAAG4529
54790_2_495+chr4: 105192794-105192814UAAAAAUGUAAAGCAGAAAA4530
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54790_2_503+chr4: 105192809-105192829GAAAAAGGAAAUUGAGUGGC4532
54790_2_504+chr4: 105192810-105192830AAAAAGGAAAUUGAGUGGCA4533
54790_2_505+chr4: 105192815-105192835GGAAAUUGAGUGGCAGGGUU4534
54790_2_509+chr4: 105192846-105192866GAAGAUAUAGUAGUCAAGUA4535
54790_2_519+chr4: 105192922-105192942CAAGCCAUGAAGUUAUCUGA4536
54790_2_521+chr4: 105192931-105192951AAGUUAUCUGAAGGAAUUGC4537
54790_2_523+chr4: 105192937-105192957UCUGAAGGAAUUGCAGGUAG4538
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54790_2_531+chr4: 105192969-105192989AAAAGACCUGGAGUAGUAAA4540
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54790_2_549+chr4: 105193065-105193085AGUGAUAUGGACAAGAACUU4542
54790_2_551+chr4: 105193081-105193101ACUUUGGAAGUUGAAUAGCA4543
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54790_2_560+chr4: 105193103-105193123GUCCAUCUGGACUAUAACAG4545
54790_2_561+chr4: 105193106-105193126CAUCUGGACUAUAACAGAGG4546
54790_2_564+chr4: 105193117-105193137UAACAGAGGAGGCUUCACAA4547
54790_2_565+chr4: 105193121-105193141AGAGGAGGCUUCACAAAGGA4548
54790_2_567+chr4: 105193128-105193148GCUUCACAAAGGAAGGUGAC4549
54790_2_568+chr4: 105193129-105193149CUUCACAAAGGAAGGUGACA4550
54790_2_570+chr4: 105193134-105193154CAAAGGAAGGUGACAGGGCA4551
54790_2_572+chr4: 105193139-105193159GAAGGUGACAGGGCAUGGCC4552
54790_2_575+chr4: 105193149-105193169GGGCAUGGCCUGGAUCCUGA4553
54790_2_577+chr4: 105193154-105193174UGGCCUGGAUCCUGAAGGAC4554
54790_2_583+chr4: 105193163-105193183UCCUGAAGGACAGGAAGAAU4555
54790_2_584+chr4: 105193164-105193184CCUGAAGGACAGGAAGAAUU4556
54790_2_589+chr4: 105193193-105193213AACAAAGAAUGACAUCCCAG4557
54790_2_595+chr4: 105193203-105193223GACAUCCCAGUGGAGAGAAG4558
54790_2_598+chr4: 105193206-105193226AUCCCAGUGGAGAGAAGUGG4559
54790_2_600+chr4: 105193207-105193227UCCCAGUGGAGAGAAGUGGA4560
54790_2_601+chr4: 105193208-105193228CCCAGUGGAGAGAAGUGGAG4561
54790_2_605+chr4: 105193224-105193244GGAGGGGAAACAGCAUGAAA4562
54790_2_610+chr4: 105193243-105193263AUGGAGUGAAAUAAGAAUGU4563
54790_2_612+chr4: 105193251-105193271AAAUAAGAAUGUUGGCCUUU4564
54790_2_613+chr4: 105193252-105193272AAUAAGAAUGUUGGCCUUUA4565
54790_2_615+chr4: 105193256-105193276AGAAUGUUGGCCUUUAGGGC4566
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54790_2_621+chr4: 105193267-105193287CUUUAGGGCAGGAAUGGGCC4569
54790_2_626+chr4: 105193273-105193293GGCAGGAAUGGGCCAGGCAG4570
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54790_2_632+chr4: 105193282-105193302GGGCCAGGCAGAGGGCAAGU4573
54790_2_635+chr4: 105193289-105193309GCAGAGGGCAAGUGGGAAGC4574
54790_2_636+chr4: 105193296-105193316GCAAGUGGGAAGCAGGAAAA4575
54790_2_637+chr4: 105193321-105193341ACCUUGUAUAAAGUUCAUGU4576
54790_2_645+chr4: 105193339-105193359GUUGGCAAAUAGAGAGAAGA4577
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54790_2_659+chr4: 105193417-105193437GCAUGCUAUCCUGAAAAUAU4582
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54790_2_686+chr4: 105193505-105193525AAUUUAAACAAAUAAGGAAA4587
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54790_2_709+chr4: 105193565-105193585AUGGAUUUUGUUAAGAGAGA4592
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54790_2_9910−chr4: 105191734-105191754UGGCAACAUCCAGGAAUCAU6120
54790_2_9913−chr4: 105191735-105191755AUGGCAACAUCCAGGAAUCA6121
54790_2_9916−chr4: 105191743-105191763UCUUGAAAAUGGCAACAUCC6122
54790_2_9920−chr4: 105191754-105191774CUUGCCCUGUGUCUUGAAAA6123
54790_2_9924−chr4: 105191794-105191814UUAAAAUUCCCAAGGUAGAG6124
54790_2_9927−chr4: 105191802-105191822AGAGUGACUUAAAAUUCCCA6125
54790_2_9941−chr4: 105191875-105191895UAAAAAUAUUAACAUGCAAG6126
54790_2_9944−chr4: 105191876-105191896CUAAAAAUAUUAACAUGCAA6127
54790_2_9947−chr4: 105191877-105191897UCUAAAAAUAUUAACAUGCA6128
54790_2_9956−chr4: 105191927-105191947UCCAGCAUGAGAGGGGAAAG6129
54790_2_9960−chr4: 105191934-105191954AAGAUUUUCCAGCAUGAGAG6130
54790_2_9962−chr4: 105191935-105191955UAAGAUUUUCCAGCAUGAGA6131
54790_2_9965−chr4: 105191936-105191956CUAAGAUUUUCCAGCAUGAG6132
54790_2_9973−chr4: 105191989-105192009AGCAAUCAUCAAGGGAGGAG6133
54790_2_9976−chr4: 105191990-105192010AAGCAAUCAUCAAGGGAGGA6134
54790_2_9978−chr4: 105191991-105192011AAAGCAAUCAUCAAGGGAGG6135
54790_2_9980−chr4: 105191994-105192014GGUAAAGCAAUCAUCAAGGG6136
54790_2_9983−chr4: 105191997-105192017UGAGGUAAAGCAAUCAUCAA6137
54790_2_9985−chr4: 105191998-105192018GUGAGGUAAAGCAAUCAUCA6138
54790_2_9989−chr4: 105192015-105192035GUCACAGUUCUCACAGAGUG6139
54790_2_10002−chr4: 105192099-105192119AUGUUAUGACUUCAUUAAGG6140
54790_2_10005−chr4: 105192102-105192122CUAAUGUUAUGACUUCAUUA6141
54790_2_10019−chr4: 105192155-105192175CUGCACUUUAUUCCUUACCC6142
54790_2_10044−chr4: 105192241-105192261UGUAAAACCUUUUCCCUCAA6143
54790_2_10054−chr4: 105192286-105192306AGAUUUUUGAGGAGAUAUGA6144
54790_2_10055−chr4: 105192287-105192307AAGAUUUUUGAGGAGAUAUG6145
54790_2_10060−chr4: 105192297-105192317AAUGCAAAACAAGAUUUUUG6146
54790_2_10070−chr4: 105192347-105192367UGCUAUUGAAAAUAUGUCAA6147
54790_2_10071−chr4: 105192348-105192368UUGCUAUUGAAAAUAUGUCA6148
54790_2_10074−chr4: 105192376-105192396UACUACUAAAAAUAAACUCU6149
54790_2_10086−chr4: 105192433-105192453UAAAUUUCGUCCCGAAUGUC6150
54790_2_10092−chr4: 105192443-105192463GAAGAAACGGUAAAUUUCGU6151
54790_2_10093−chr4: 105192444-105192464AGAAGAAACGGUAAAUUUCG6152
54790_2_10101−chr4: 105192510-105192530GAUAUACAACCCGUUACAUG6153
54790_2_10103−chr4: 105192521-105192541AACUCUUGAAUGAUAUACAA6154
54790_2_10104−chr4: 105192522-105192542UAACUCUUGAAUGAUAUACA6155
54790_2_10111−chr4: 105192573-105192593AAAAGCAACAUUAAUAAAAG6156
54790_2_10124−chr4: 105192638-105192658UUCUCACGGACCAUAAACCG6157
54790_2_10126−chr4: 105192642-105192662GAUCUUCUCACGGACCAUAA6158
54790_2_10127−chr4: 105192649-105192669GAUCAAGGAUCUUCUCACGG6159
54790_2_10140−chr4: 105192706-105192726UACCUAAGAUUCGAGUUGUU6160
54790_2_10142−chr4: 105192707-105192727UUACCUAAGAUUCGAGUUGU6161
54790_2_10145−chr4: 105192725-105192745CACAGACAGAGAAUGAGAUU6162
54790_2_10164−chr4: 105192779-105192799AAAAUUUUGAAUCGUGAAGA6163
54790_2_10195−chr4: 105192929-105192949UUAAGGAAGUCUAUUGAAGU6164
54790_2_10203−chr4: 105192970-105192990UUUUAGAUGAGGUCCAGAAA6165
54790_2_10204−chr4: 105192978-105192998AUAAAACCUUUUAGAUGAGG6166
54790_2_10220−chr4: 105193108-105193128CUCCUCUGUUAUAGUCCAGA6167
54790_2_10229−chr4: 105193160-105193180CUUCCUGUCCUUCAGGAUCC6168
54790_2_10230−chr4: 105193167-105193187CCCAAUUCUUCCUGUCCUUC6169
54790_2_10239−chr4: 105193211-105193231CCCCUCCACUUCUCUCCACU6170
54790_2_10240−chr4: 105193212-105193232UCCCCUCCACUUCUCUCCAC6171
54790_2_10250−chr4: 105193269-105193289CUGGCCCAUUCCUGCCCUAA6172
54790_2_10253−chr4: 105193288-105193308CUUCCCACUUGCCCUCUGCC6173
54790_2_10262−chr4: 105193325-105193345GCCAACAUGAACUUUAUACA6174
54790_2_10276−chr4: 105193380-105193400CUUUAGGAUUUUACUAAAUU6175
54790_2_10279−chr4: 105193396-105193416AUAAUCUUUAGCUUGACUUU6176
54790_2_10286−chr4: 105193429-105193449AAUUAUUCCCCAAUAUUUUC6177
54790_2_10358−chr4: 105193876-105193896UGUACUAUGUUAGUAUUACA6178
54790_2_10364−chr4: 105193914-105193934UAUUAUAAAAAUACAAAAUU6179
54790_2_10374−chr4: 105193977-105193997AACCUGAUCGACUACAGAUU6180
54790_2_10379−chr4: 105193996-105194016GAAGGUGUUUUACUUGAUUA6181
54790_2_10383−chr4: 105194030-105194050AUUUCAGUACAUUGUAGAGA6182
54790_2_10384−chr4: 105194031-105194051UAUUUCAGUACAUUGUAGAG6183
54790_2_10387−chr4: 105194056-105194076AAUCUAUGAUCGAUCUCCGU6184
54790_2_10388−chr4: 105194061-105194081GGUUCAAUCUAUGAUCGAUC6185
54790_2_10390−chr4: 105194089-105194109GAGUCUCAGUAUCCUCUGGA6186
54790_2_10391−chr4: 105194090-105194110AGAGUCUCAGUAUCCUCUGG6187
54790_2_10396−chr4: 105194098-105194118GCAGGAGGAGAGUCUCAGUA6188
54790_2_10411−chr4: 105194113-105194133AUUAUUUUUUUAUUAGCAGG6189
54790_2_10414−chr4: 105194116-105194136UUUAUUAUUUUUUUAUUAGC6190
54790_2_10418−chr4: 105194204-105194224GGCUACAAGAGAGUGCUAAC6191
54790_2_10423−chr4: 105194225-105194245GUGUAUGUUAAUUAGAAAAA6192
54790_2_10428−chr4: 105194254-105194274UAGAUCUGUUUCAUGAGAAA6193
54790_2_10429−chr4: 105194255-105194275UUAGAUCUGUUUCAUGAGAA6194
54790_2_10441−chr4: 105194323-105194343CUUCAACAAUGACUAAAGGU6195
54790_2_10444−chr4: 105194324-105194344ACUUCAACAAUGACUAAAGG6196
54790_2_10446−chr4: 105194327-105194347GAAACUUCAACAAUGACUAA6197
54790_2_10449−chr4: 105194349-105194369AAAAGAUAACAUUGUAAAUC6198
54790_2_10470−chr4: 105194464-105194484CUGUAGGGUGAUGGUUUUUU6199
54790_2_10472−chr4: 105194465-105194485CCUGUAGGGUGAUGGUUUUU6200
54790_2_10475−chr4: 105194473-105194493AUUUAUUUCCUGUAGGGUGA6201
54790_2_10476−chr4: 105194479-105194499AGUGUGAUUUAUUUCCUGUA6202
54790_2_10477−chr4: 105194480-105194500GAGUGUGAUUUAUUUCCUGU6203
54790_2_10482−chr4: 105194516-105194536GAGAAAUCAGUAGCCAGAUC6204
54790_2_10491−chr4: 105194551-105194571AAGUCUUAAAGUCUAAGUAU6205
54790_2_10498−chr4: 105194585-105194605GUUCAUAAGAAUGACCUGUA6206
54790_2_10502−chr4: 105194614-105194634GCUUGCUAGAACAAUGACUA6207
54790_2_10506−chr4: 105194636-105194656ACUCAAAGAAUAAACUGCUC6208
54790_2_10517−chr4: 105194685-105194705GCACUGUAUUAUGAUCUCUA6209
54790_2_10533−chr4: 105194777-105194797UACAUGUCUGCUCACUUGCU6210
54790_2_10541−chr4: 105194843-105194863AUACCAUGUGGCAUGUGUAA6211
54790_2_10545−chr4: 105194855-105194875AUGACUUGUAUCAUACCAUG6212
54790_2_10553−chr4: 105194901-105194921CAAGACACCAUGUAUAAGAG6213
54790_2_10556−chr4: 105194938-105194958GAGACUACUGAUACCACUCU6214
54790_2_10557−chr4: 105194939-105194959AGAGACUACUGAUACCACUC6215
54790_2_10565−chr4: 105194966-105194986GAUGUUUAAUUCAGUCUCUU6216
54790_2_10566−chr4: 105194967-105194987AGAUGUUUAAUUCAGUCUCU6217
54790_2_10570−chr4: 105194997-105195017CAGUCUAUUUACGGUGUUCU6218
54790_2_10578−chr4: 105195022-105195042ACACUUAAAUCCCUAACGGU6219
54790_2_10579−chr4: 105195032-105195052AUGUCGAUAAACACUUAAAU6220
54790_2_10581−chr4: 105195033-105195053UAUGUCGAUAAACACUUAAA6221
54790_2_10585−chr4: 105195081-105195101AUCAAAGGACACAUCAUAUG6222
54790_2_10591−chr4: 105195096-105195116UUUACUUGUUCUAAAAUCAA6223
54790_2_10598−chr4: 105195139-105195159AUCACUUUUACUGAAAGUAU6224
54790_2_10607−chr4: 105195179-105195199ACUAUAAAGUGGAAAACUAC6225
54790_2_10612−chr4: 105195206-105195226UUUCUAGGACUCUAGUUGUC6226
54790_2_10642−chr4: 105195339-105195359CACAUUUUGAGAAAAAUGUC6227
54790_2_10661−chr4: 105195460-105195480GUUAGAGGGUGUCUAUGACU6228
54790_2_10668−chr4: 105195486-105195506AACUAUAGGUACCCCCCAGG6229
54790_2_10670−chr4: 105195492-105195512GUCUAAAACUAUAGGUACCC6230
54790_2_10671−chr4: 105195493-105195513UGUCUAAAACUAUAGGUACC6231
54790_2_10672−chr4: 105195494-105195514GUGUCUAAAACUAUAGGUAC6232
54790_2_10675−chr4: 105195495-105195515GGUGUCUAAAACUAUAGGUA6233
54790_2_10677−chr4: 105195496-105195516AGGUGUCUAAAACUAUAGGU6234
54790_2_10683−chr4: 105195520-105195540AUAAAAUAUAUUCUCUGAAC6235
54790_2_10688−chr4: 105195572-105195592UACUAAGCUUCAUAUACCCU6236
54790_2_10689−chr4: 105195573-105195593CUACUAAGCUUCAUAUACCC6237
54790_2_10691−chr4: 105195576-105195596UCUCUACUAAGCUUCAUAUA6238
54790_2_10694−chr4: 105195577-105195597CUCUCUACUAAGCUUCAUAU6239
54790_2_10702−chr4: 105195623-105195643AUUAUUGAUGAAUGUAUCGU6240
54790_2_10714−chr4: 105195713-105195733GUUUUAUGAGUCUUUUUUUU6241
54790_2_10720−chr4: 105195754-105195774AAGUACCUAAGGUCGUAGAC6242
54790_2_10722−chr4: 105195770-105195790GUCGGGGGGUACCCAUAAGU6243
54790_2_10725−chr4: 105195779-105195799CAUUAUUCAGUCGGGGGGUA6244
54790_2_10726−chr4: 105195780-105195800ACAUUAUUCAGUCGGGGGGU6245
54790_2_10735−chr4: 105195836-105195856UCAAGGACUAUACGUGUCCU6246
54790_2_10736−chr4: 105195853-105195873AAGACUCCUACCAAGAUUCA6247
54790_2_10743−chr4: 105195901-105195921GAGUCAAGAUCUUGAGAAGA6248
54790_2_10747−chr4: 105195923-105195943GCACGUGUACAAGUGGGGGU6249
54790_2_10750−chr4: 105195927-105195947AUGUGCACGUGUACAAGUGG6250
54790_2_10751−chr4: 105195928-105195948UAUGUGCACGUGUACAAGUG6251
54790_2_10753−chr4: 105195929-105195949GUAUGUGCACGUGUACAAGU6252
54790_2_10755−chr4: 105195930-105195950AGUAUGUGCACGUGUACAAG6253
54790_2_10760−chr4: 105195974-105195994CCACUCGUCCUGAAUUCCUU6254
54790_2_10761−chr4: 105195975-105195995ACCACUCGUCCUGAAUUCCU6255
54790_2_10763−chr4: 105195979-105195999UUCGACCACUCGUCCUGAAU6256
54790_2_10766−chr4: 105195987-105196007AUCCUUCGUUCGACCACUCG6257
54790_2_10769−chr4: 105195995-105196015GUUACGUUAUCCUUCGUUCG6258
54790_2_10772−chr4: 105196006-105196026AACUUACGAGAGUUACGUUA6259
54790_2_10777−chr4: 105196029-105196049CCAUCUUCAAGAACCAGAUG6260
54790_2_10778−chr4: 105196037-105196057UUUUUAUACCAUCUUCAAGA6261
54790_2_10784−chr4: 105196050-105196070GCCCAUCUCCACCUUUUUAU6262
54790_2_10786−chr4: 105196060-105196080ACUGUGUUUUGCCCAUCUCC6263
54790_2_10788−chr4: 105196063-105196083UAAACUGUGUUUUGCCCAUC6264
54790_2_10790−chr4: 105196069-105196089UAUGUCUAAACUGUGUUUUG6265
54790_2_10791−chr4: 105196070-105196090AUAUGUCUAAACUGUGUUUU6266
54790_2_10792−chr4: 105196071-105196091GAUAUGUCUAAACUGUGUUU6267
54790_2_10795−chr4: 105196093-105196113ACUCUGAAGAAUGAAAAGAA6268
54790_2_10805−chr4: 105196123-105196143UAGGAAAUAAUUUAUGGAAG6269
54790_2_10807−chr4: 105196129-105196149AACAAUUAGGAAAUAAUUUA6270
54790_2_10809−chr4: 105196142-105196162CAGAGGCAGAGGGAACAAUU6271
54790_2_10812−chr4: 105196152-105196172AAAAAAAGAACAGAGGCAGA6272
54790_2_10814−chr4: 105196153-105196173AAAAAAAAGAACAGAGGCAG6273
54790_2_10818−chr4: 105196159-105196179AGAAAAAAAAAAAAGAACAG6274
54790_2_10829−chr4: 105196200-105196220ACUUAAGAAUGGGCAUACAG6275
54790_2_10831−chr4: 105196210-105196230UCAGAUUUGCACUUAAGAAU6276
54790_2_10832−chr4: 105196211-105196231GUCAGAUUUGCACUUAAGAA6277
54790_2_10836−chr4: 105196233-105196253AUAUUAAGAAGGGGUAUAGA6278
54790_2_10837−chr4: 105196242-105196262AAAGAAAGGAUAUUAAGAAG6279
54790_2_10838−chr4: 105196243-105196263AAAAGAAAGGAUAUUAAGAA6280
54790_2_10839−chr4: 105196244-105196264UAAAAGAAAGGAUAUUAAGA6281
54790_2_10844−chr4: 105196256-105196276AAUGGGUAUCCAUAAAAGAA6282
54790_2_10849−chr4: 105196273-105196293CCUUUAAUAAAGUCUGAAAU6283
54790_2_10850−chr4: 105196274-105196294UCCUUUAAUAAAGUCUGAAA6284
54790_2_10855−chr4: 105196307-105196327CAAGUGGUGAGGUGGGGAGG6285
54790_2_10858−chr4: 105196308-105196328UCAAGUGGUGAGGUGGGGAG6286
54790_2_10859−chr4: 105196309-105196329UUCAAGUGGUGAGGUGGGGA6287
54790_2_10862−chr4: 105196310-105196330CUUCAAGUGGUGAGGUGGGG6288
54790_2_10864−chr4: 105196313-105196333AAACUUCAAGUGGUGAGGUG6289
54790_2_10868−chr4: 105196314-105196334AAAACUUCAAGUGGUGAGGU6290
54790_2_10870−chr4: 105196315-105196335AAAAACUUCAAGUGGUGAGG6291
54790_2_10872−chr4: 105196318-105196338UGCAAAAACUUCAAGUGGUG6292
54790_2_10875−chr4: 105196323-105196343CUAAUUGCAAAAACUUCAAG6293
54790_2_10883−chr4: 105196402-105196422ACUCUGAAAAGGGGAUAAGU6294
54790_2_10885−chr4: 105196411-105196431UUCAGGGCCACUCUGAAAAG6295
54790_2_10886−chr4: 105196412-105196432AUUCAGGGCCACUCUGAAAA6296
54790_2_10888−chr4: 105196413-105196433UAUUCAGGGCCACUCUGAAA6297
54790_2_10894−chr4: 105196427-105196447UGGGUUCACAGAGCUAUUCA6298
54790_2_10895−chr4: 105196428-105196448CUGGGUUCACAGAGCUAUUC6299
54790_2_10900−chr4: 105196446-105196466ACUGAGUUCUUCAGAUUCCU6300
54790_2_10903−chr4: 105196447-105196467UACUGAGUUCUUCAGAUUCC6301
54790_2_10911−chr4: 105196477-105196497AUCUACUUUCUGUAGGCUGA6302
54790_2_10912−chr4: 105196484-105196504GAGUUUGAUCUACUUUCUGU6303
54790_2_10915−chr4: 105196520-105196540GAGUAACCAGGAGCCAGAUC6304
54790_2_10920−chr4: 105196532-105196552GAGGAAUUUGAAGAGUAACC6305
54790_2_10925−chr4: 105196551-105196571GAAGGGACAAUAUAGUAAGG6306
54790_2_10928−chr4: 105196554-105196574UCUGAAGGGACAAUAUAGUA6307
54790_2_10932−chr4: 105196568-105196588UAAAGAUUUACAAAUCUGAA6308
54790_2_10933−chr4: 105196569-105196589GUAAAGAUUUACAAAUCUGA6309
54790_2_10938−chr4: 105196591-105196611GUGUGUAAAAUACGAUGUCA6310
54790_2_10939−chr4: 105196618-105196638GGAGAGGAACAGCGGUACAA6311
54790_2_10941−chr4: 105196626-105196646GUUCAUCAGGAGAGGAACAG6312
54790_2_10943−chr4: 105196634-105196654AAAGGGAAGUUCAUCAGGAG6313
54790_2_10948−chr4: 105196639-105196659AGAGAAAAGGGAAGUUCAUC6314
54790_2_10950−chr4: 105196651-105196671GCUGUGUAGUUAAGAGAAAA6315
54790_2_10952−chr4: 105196652-105196672AGCUGUGUAGUUAAGAGAAA6316
54790_2_10965−chr4: 105196722-105196742AUGUCAUUCAUCCUACAAAC6317
54790_2_10969−chr4: 105196732-105196752UUGUUUACUGAUGUCAUUCA6318
54790_2_10973−chr4: 105196766-105196786UCCUUAAAGUCUUAGACGUU6319
54790_2_10979−chr4: 105196786-105196806GUUCUACGUCGGAAACGGGA6320
54790_2_10995−chr4: 105196917-105196937AAGUUGCCAGUAGGGGGAGA6321
54790_2_10996−chr4: 105196918-105196938GAAGUUGCCAGUAGGGGGAG6322
54790_2_11000−chr4: 105196923-105196943AGGAAGAAGUUGCCAGUAGG6323
54790_2_11003−chr4: 105196924-105196944UAGGAAGAAGUUGCCAGUAG6324
54790_2_11005−chr4: 105196925-105196945GUAGGAAGAAGUUGCCAGUA6325
54790_2_11008−chr4: 105196926-105196946AGUAGGAAGAAGUUGCCAGU6326
54790_2_11014−chr4: 105196943-105196963CUGUAUCUAUUUUAAGAAGU6327
54790_2_11021−chr4: 105196972-105196992ACCUCUUCCCUCCACUUAGU6328
54790_2_11022−chr4: 105196973-105196993CACCUCUUCCCUCCACUUAG6329
54790_2_11038−chr4: 105197075-105197095CUUAUAAUUAAGUAUCUCUG6330
54790_2_11043−chr4: 105197121-105197141UACUUUAGUGAAAAAAAUGU6331
54790_2_11050−chr4: 105197145-105197165GCAACACAUUUAAUUUUGAU6332
54790_2_11076−chr4: 105197346-105197366UAUUCAUGUAUUUCUCACUA6333
54790_2_11083−chr4: 105197424-105197444AGAACACAACCAAAAACUGC6334
54790_2_11093−chr4: 105197512-105197532GGACAGCACUCUCAAACAUA6335
54790_2_11095−chr4: 105197533-105197553CAGCCACAUCACAAAGCACC6336
54790_2_11115−chr4: 105197639-105197659CACUUUUUACUCUUUGGUCA6337
54790_2_11117−chr4: 105197640-105197660UCACUUUUUACUCUUUGGUC6338
54790_2_11120−chr4: 105197645-105197665AAGAAUCACUUUUUACUCUU6339
54790_2_11126−chr4: 105197673-105197693UUUACUUUCCUCUAUAGCUA6340
54790_2_11134−chr4: 105197703-105197723UUUAAUUCUACAUUUGAUGU6341
54790_2_11135−chr4: 105197704-105197724AUUUAAUUCUACAUUUGAUG6342
54790_2_11157−chr4: 105197796-105197816AAAACCUUUCAGAGACCAUC6343
54790_2_11161−chr4: 105197820-105197840UUACUCUGAAAGUGAGUAAA6344
54790_2_11163−chr4: 105197821-105197841CUUACUCUGAAAGUGAGUAA6345
54790_2_11174−chr4: 105197887-105197907AACUUUUGGAAAAACAGAAA6346
54790_2_11175−chr4: 105197888-105197908AAACUUUUGGAAAAACAGAA6347
54790_2_11181−chr4: 105197901-105197921CUUUCAAAAAAUAAAACUUU6348
54790_2_11189−chr4: 105197931-105197951UAAUUUUUCAAAUGUCUAAA6349
54790_2_11195−chr4: 105197989-105198009CUUUUCUACGUUGCUACUCU6350
54790_2_11204−chr4: 105198024-105198044UUAUUAAAUACUUACUAUGU6351
54790_2_11206−chr4: 105198059-105198079GUCCUCACUCGAUGGAGUGG6352
54790_2_11210−chr4: 105198078-105198098AGGGUUUAACGACCCUAAUG6353
54790_2_11212−chr4: 105198086-105198106GGAGCCGGAGGGUUUAACGA6354
54790_2_11213−chr4: 105198087-105198107CGGAGCCGGAGGGUUUAACG6355
54790_2_11217−chr4: 105198103-105198123GAGUCCACUAGGUGGGCGGA6356
54790_2_11218−chr4: 105198120-105198140CCAGAGUUUGAGAACUGGAG6357
54790_2_11221−chr4: 105198141-105198161AAAGUGGUAUGACCAGUCCG6358
54790_2_11222−chr4: 105198145-105198165CCCCAAAGUGGUAUGACCAG6359
54790_2_11224−chr4: 105198150-105198170CUCUACCCCAAAGUGGUAUG6360
54790_2_11231−chr4: 105198164-105198184AACGUAAAAAUCAUCUCUAC6361
54790_2_11232−chr4: 105198165-105198185AAACGUAAAAAUCAUCUCUA6362
54790_2_11233−chr4: 105198166-105198186AAAACGUAAAAAUCAUCUCU6363
54790_2_11238−chr4: 105198212-105198232AGGGCUCAUCGACCAUAAUA6364
54790_2_11239−chr4: 105198221-105198241CGGAGUCGGAGGGCUCAUCG6365
54790_2_11244−chr4: 105198285-105198305CCUCACGUUGCCGUGCUAGA6366
54790_2_11247−chr4: 105198296-105198316AACGAGUCCGACCUCACGUU6367
54790_2_11250−chr4: 105198306-105198326AAGUGAGAACAACGAGUCCG6368
54790_2_11253−chr4: 105198310-105198330CUCAAAGUGAGAACAACGAG6369
54790_2_11283−chr4: 105198404-105198424UUGAUAGUUUUCCUUUUCAU6370
54790_2_11300−chr4: 105198486-105198506CAUAUUUUAGUUUCUGACUU6371
54790_2_11311−chr4: 105198539-105198559UUCCUUCUGUCUCCUUUAAC6372
54790_2_11323−chr4: 105198584-105198604AUUUUCUUGCCCUUAUUUUC6373
54790_2_11343−chr4: 105198674-105198694GUUCAUUUUUUCAGCCUACA6374
54790_2_11346−chr4: 105198700-105198720CAAGGACGUACCAUACCUUU6375
54790_2_11347−chr4: 105198701-105198721CCAAGGACGUACCAUACCUU6376
54790_2_11351−chr4: 105198706-105198726UUCUUCCAAGGACGUACCAU6377
54790_2_11353−chr4: 105198711-105198731GUCAUUUCUUCCAAGGACGU6378
54790_2_11355−chr4: 105198722-105198742AGAAUCCUUACGUCAUUUCU6379
54790_2_11359−chr4: 105198738-105198758CCACGAUCUGAUCAGGAGAA6380
54790_2_11363−chr4: 105198759-105198779UAAUGGUGUUCAUAGGUUAA6381
54790_2_11378−chr4: 105198893-105198913AUUAUAAUUAAGUAUCUCUG6382
54790_2_11389−chr4: 105198965-105198985GCAACACAUUUAAUUUUGGU6383
54790_2_11391−chr4: 105198969-105198989AACUGCAACACAUUUAAUUU6384
54790_2_11401−chr4: 105199050-105199070UUUAUGUUCAUCAAUACUAU6385
54790_2_11423−chr4: 105199181-105199201CACCAAACUUUAAUAUUUAA6386
54790_2_11425−chr4: 105199182-105199202ACACCAAACUUUAAUAUUUA6387
54790_2_11430−chr4: 105199229-105199249AAUUAGAAGAGAGCCCUAUA6388
54790_2_11437−chr4: 105199253-105199273AAUUAUCUACACGUCAUAGG6389
54790_2_11446−chr4: 105199343-105199363UUUUUUCUGUUUUUGGAAAC6390
54790_2_11455−chr4: 105199400-105199420UUUAGUGUCAGUGUUUCACU6391
54790_2_11466−chr4: 105199466-105199486UCCCUGAACUUCUUUGUUCU6392
54790_2_11475−chr4: 105199485-105199505GGUAUUUAAAGGAAUUUCCU6393
54790_2_11477−chr4: 105199486-105199506AGGUAUUUAAAGGAAUUUCC6394
54790_2_11480−chr4: 105199489-105199509UAAAGGUAUUUAAAGGAAUU6395
54790_2_11483−chr4: 105199518-105199538UUUUAAGCCACUUGAUGGUA6396
54790_2_11487−chr4: 105199523-105199543UUUUCUUUUAAGCCACUUGA6397
54790_2_11490−chr4: 105199556-105199576GUGCACAUGAGGACUUGAAU6398
54790_2_11495−chr4: 105199599-105199619GUUGUUUGAGGGUACUGGGU6399
54790_2_11498−chr4: 105199639-105199659CCCAUGAUCCGAAUUAUGGA6400
54790_2_11499−chr4: 105199640-105199660ACCCAUGAUCCGAAUUAUGG6401
54790_2_11501−chr4: 105199652-105199672UUUUUAUUGAUUACCCAUGA6402
54790_2_11502−chr4: 105199659-105199679CUAGUCCUUUUUAUUGAUUA6403
54790_2_11503−chr4: 105199660-105199680CCUAGUCCUUUUUAUUGAUU6404
54790_2_11505−chr4: 105199675-105199695CACCCUCCUCCCUCUCCUAG6405
54790_2_11508−chr4: 105199681-105199701ACCUCCCACCCUCCUCCCUC6406
54790_2_11511−chr4: 105199686-105199706CUCCCACCUCCCACCCUCCU6407
54790_2_11513−chr4: 105199687-105199707UCUCCCACCUCCCACCCUCC6408
54790_2_11516−chr4: 105199690-105199710UAGUCUCCCACCUCCCACCC6409
54790_2_11520−chr4: 105199693-105199713GGAUAGUCUCCCACCUCCCA6410
54790_2_11521−chr4: 105199694-105199714CGGAUAGUCUCCCACCUCCC6411
54790_2_11524−chr4: 105199697-105199717CCCCGGAUAGUCUCCCACCU6412
54790_2_11525−chr4: 105199698-105199718GCCCCGGAUAGUCUCCCACC6413
54790_2_11527−chr4: 105199701-105199721GUGGCCCCGGAUAGUCUCCC6414
54790_2_11530−chr4: 105199704-105199724UGUGUGGCCCCGGAUAGUCU6415
54790_2_11531−chr4: 105199705-105199725GUGUGUGGCCCCGGAUAGUC6416
54790_2_11534−chr4: 105199716-105199736CUCCCCUUGUUGUGUGUGGC6417
54790_2_11535−chr4: 105199717-105199737UCUCCCCUUGUUGUGUGUGG6418
54790_2_11536−chr4: 105199718-105199738GUCUCCCCUUGUUGUGUGUG6419
54790_2_11540−chr4: 105199733-105199753CUCCUGUAUACCUGUGUCUC6420
54790_2_11541−chr4: 105199734-105199754ACUCCUGUAUACCUGUGUCU6421
54790_2_11543−chr4: 105199735-105199755UACUCCUGUAUACCUGUGUC6422
54790_2_11547−chr4: 105199744-105199764UCGAUUUACUACUCCUGUAU6423
54790_2_11550−chr4: 105199752-105199772AUUCACCCUCGAUUUACUAC6424
54790_2_11555−chr4: 105199767-105199787CGUACAAGAGUGAAUAUUCA6425
54790_2_11556−chr4: 105199768-105199788ACGUACAAGAGUGAAUAUUC6426
54790_2_11561−chr4: 105199808-105199828AUAGGUAUCGUUUGAUUGUA6427
54790_2_11567−chr4: 105199835-105199855UACCUGUACCUACCUCGACC6428
54790_2_11570−chr4: 105199838-105199858ACGUACCUGUACCUACCUCG6429
54790_2_11573−chr4: 105199844-105199864CAAAAAACGUACCUGUACCU6430
54790_2_11576−chr4: 105199848-105199868AGUACAAAAAACGUACCUGU6431
54790_2_11578−chr4: 105199854-105199874UAUUCUAGUACAAAAAACGU6432
54790_2_11583−chr4: 105199901-105199921UGACACAAUAUAUAUGUGGU6433
54790_2_11586−chr4: 105199934-105199954UUACGGGUGGUUAUUAUCUG6434
54790_2_11590−chr4: 105199967-105199987AUAAGUGUUAUCGUUUCUGU6435
54790_2_11599−chr4: 105200045-105200065GUGAUGACCCAUAUAUGGUU6436
54790_2_11602−chr4: 105200058-105200078UUGGGUCGUUGGGGUGAUGA6437
54790_2_11603−chr4: 105200059-105200079GUUGGGUCGUUGGGGUGAUG6438
54790_2_11610−chr4: 105200129-105200149CAUUUAAUCAAGUUGGUAAC6439
54790_2_11616−chr4: 105200155-105200175UUGUGAAUAUACGAUAACCA6440
54790_2_11618−chr4: 105200156-105200176CUUGUGAAUAUACGAUAACC6441
54790_2_11620−chr4: 105200159-105200179UUCCUUGUGAAUAUACGAUA6442
54790_2_11624−chr4: 105200178-105200198AUCACUCCAACGCCUCUUUU6443
54790_2_11627−chr4: 105200187-105200207UAUUGUGCAAUCACUCCAAC6444
54790_2_11630−chr4: 105200193-105200213GUUUUUUAUUGUGCAAUCAC6445
54790_2_11634−chr4: 105200231-105200251GGUAGAGUGUGGUCAGUCCU6446
54790_2_11635−chr4: 105200235-105200255CUAUGGUAGAGUGUGGUCAG6447
54790_2_11644−chr4: 105200327-105200347AUGUUUUCUUCUGUAUGUAC6448
54790_2_11649−chr4: 105200366-105200386GGGUAACUUUUUCACCCGUU6449
54790_2_11651−chr4: 105200372-105200392UUGUAGGGGUAACUUUUUCA6450
54790_2_11652−chr4: 105200373-105200393UUUGUAGGGGUAACUUUUUC6451
54790_2_11658−chr4: 105200414-105200434AUAUUCCUAGAAUUUAAAUG6452
54790_2_11661−chr4: 105200430-105200450UUAUCAUAGGUCGUAGAUAU6453
54790_2_11669−chr4: 105200482-105200502UUUGUCUGUUGGAUGUCUUA6454
54790_2_11672−chr4: 105200483-105200503UUUUGUCUGUUGGAUGUCUU6455
54790_2_11682−chr4: 105200557-105200577CAUUCGUUUUUAAGUGUUUA6456
54790_2_11684−chr4: 105200558-105200578UCAUUCGUUUUUAAGUGUUU6457
54790_2_11689−chr4: 105200617-105200637AAAAAAAAACAGUGUGACCU6458
54790_2_11692−chr4: 105200618-105200638CAAAAAAAAACAGUGUGACC6459
54790_2_11696−chr4: 105200704-105200724ACAUAGUGGUGUGAGGUCUG6460
54790_2_11701−chr4: 105200744-105200764ACGAACUUGGGCCUUACACC6461
54790_2_11702−chr4: 105200747-105200767UUAACGAACUUGGGCCUUAC6462
54790_2_11706−chr4: 105200754-105200774CGUCUUCUUAACGAACUUGG6463
54790_2_11712−chr4: 105200776-105200796GGGUCGAUGAGUCCUCCGAC6464
54790_2_11714−chr4: 105200782-105200802ACAUCAGGGUCGAUGAGUCC6465
54790_2_11716−chr4: 105200785-105200805CGGACAUCAGGGUCGAUGAG6466
54790_2_11719−chr4: 105200813-105200833GUUUUUAAUCGACCCGUACC6467
54790_2_11720−chr4: 105200816-105200836UAUGUUUUUAAUCGACCCGU6468
54790_2_11723−chr4: 105200821-105200841AUUUUUAUGUUUUUAAUCGA6469
54790_2_11724−chr4: 105200822-105200842GAUUUUUAUGUUUUUAAUCG6470
54790_2_11727−chr4: 105200861-105200881UCUCUGGUAGGACCGGUUGU6471
54790_2_11728−chr4: 105200870-105200890AGUUCUCUAUCUCUGGUAGG6472
54790_2_11734−chr4: 105200905-105200925CGUGAAACCCUCCGACUCCG6473
54790_2_11735−chr4: 105200906-105200926UCGUGAAACCCUCCGACUCC6474
54790_2_11737−chr4: 105200909-105200929GGGUCGUGAAACCCUCCGAC6475
54790_2_11739−chr4: 105200915-105200935ACAUUAGGGUCGUGAAACCC6476
54790_2_11740−chr4: 105200918-105200938CGGACAUUAGGGUCGUGAAA6477
54790_2_11743−chr4: 105200919-105200939UCGGACAUUAGGGUCGUGAA6478
54790_2_11745−chr4: 105200946-105200966UGACCUGGCCGGUCCACACC6479
54790_2_11746−chr4: 105200949-105200969GUAUGACCUGGCCGGUCCAC6480
54790_2_11749−chr4: 105200954-105200974UAAAAGUAUGACCUGGCCGG6481
54790_2_11752−chr4: 105200959-105200979UUGAUUAAAAGUAUGACCUG6482
54790_2_11753−chr4: 105200960-105200980UUUGAUUAAAAGUAUGACCU6483
54790_2_11754−chr4: 105200961-105200981UUUUGAUUAAAAGUAUGACC6484
54790_2_11773−chr4: 105201087-105201107AACAACAUGGAUUUCAACCG6485
54790_2_11775−chr4: 105201100-105201120GGUUGAAGGAUUCAACAACA6486
54790_2_11778−chr4: 105201114-105201134CUCAGUCCUCAAGGGGUUGA6487
54790_2_11782−chr4: 105201121-105201141GGGAAUUCUCAGUCCUCAAG6488
54790_2_11783−chr4: 105201122-105201142AGGGAAUUCUCAGUCCUCAA6489
54790_2_11785−chr4: 105201123-105201143AAGGGAAUUCUCAGUCCUCA6490
54790_2_11790−chr4: 105201141-105201161GAUUCAGACAGAUAAUUAAA6491
54790_2_11793−chr4: 105201142-105201162UGAUUCAGACAGAUAAUUAA6492
54790_2_11812−chr4: 105201239-105201259AAGAGAUAAUUUUGUUUAAU6493
54790_2_11829−chr4: 105201284-105201304CCUAAAUUACACAUUUGUGG6494
54790_2_11830−chr4: 105201285-105201305UCCUAAAUUACACAUUUGUG6495
54790_2_11833−chr4: 105201286-105201306UUCCUAAAUUACACAUUUGU6496
54790_2_11834−chr4: 105201287-105201307AUUCCUAAAUUACACAUUUG6497
54790_2_11851−chr4: 105201369-105201389AUACUUUCCUUAAACUUUUU6498
54790_2_11859−chr4: 105201461-105201481CAGUAAUUGAGCACUGAAAU6499
54790_2_11861−chr4: 105201462-105201482ACAGUAAUUGAGCACUGAAA6500
54790_2_11882−chr4: 105201535-105201555AUAAGCAAUACUUCCACUUG6501
54790_2_11888−chr4: 105201587-105201607GUCCUUAAAACCCCUCAGUA6502
54790_2_11900−chr4: 105201658-105201678AUUGAAUUCUAGCCUCAACU6503
54790_2_11907−chr4: 105201686-105201706UGAUACCAUUUUAACUGUAU6504
54790_2_11910−chr4: 105201727-105201747UUUUUUUUUUUUUUUGGUCC6505
54790_2_11912−chr4: 105201733-105201753UUUUUUUUUUUUUUUUUUUU6506
54790_2_11916−chr4: 105201777-105201797ACGUGGCGUCAGACCCGUUG6507
54790_2_11918−chr4: 105201784-105201804UCCGGUGACGUGGCGUCAGA6508
54790_2_11919−chr4: 105201785-105201805GUCCGGUGACGUGGCGUCAG6509
54790_2_11922−chr4: 105201804-105201824CCGACGUCACUCGGAGUUAG6510
54790_2_11924−chr4: 105201825-105201845GUGGACUCGGACCCUUCAAC6511
54790_2_11927−chr4: 105201834-105201854ACCCUCCUAGUGGACUCGGA6512
54790_2_11929−chr4: 105201835-105201855CACCCUCCUAGUGGACUCGG6513
54790_2_11932−chr4: 105201850-105201870UGAGACCUUCGACUCCACCC6514
54790_2_11934−chr4: 105201853-105201873CGAUGAGACCUUCGACUCCA6515
54790_2_11937−chr4: 105201854-105201874UCGAUGAGACCUUCGACUCC6516
54790_2_11939−chr4: 105201857-105201877GAGUCGAUGAGACCUUCGAC6517
54790_2_11941−chr4: 105201866-105201886GGGACACCAGAGUCGAUGAG6518
54790_2_11944−chr4: 105201881-105201901CCCCACCACCGUACGGGGAC6519
54790_2_11946−chr4: 105201894-105201914UUUUUUAAUCGGUCCCCACC6520
54790_2_11947−chr4: 105201897-105201917AUGUUUUUUAAUCGGUCCCC6521
54790_2_11948−chr4: 105201900-105201920UUUAUGUUUUUUAAUCGGUC6522
54790_2_11949−chr4: 105201901-105201921UUUUAUGUUUUUUAAUCGGU6523
54790_2_11950−chr4: 105201902-105201922UUUUUAUGUUUUUUAAUCGG6524
54790_2_11955−chr4: 105201943-105201963ACGCUUGUCGGACCCGUUGU6525
54790_2_11956−chr4: 105201951-105201971GUCCUCAAACGCUUGUCGGA6526
54790_2_11957−chr4: 105201952-105201972GGUCCUCAAACGCUUGUCGG6527
54790_2_11963−chr4: 105201970-105201990GUCCACCUAACGAACUCCGG6528
54790_2_11965−chr4: 105201975-105201995GCUCCGUCCACCUAACGAAC6529
54790_2_11969−chr4: 105201986-105202006GAAACCCUUCGGCUCCGUCC6530
54790_2_11972−chr4: 105201989-105202009CGUGAAACCCUUCGGCUCCG6531
54790_2_11973−chr4: 105201993-105202013AGGUCGUGAAACCCUUCGGC6532
54790_2_11977−chr4: 105202002-105202022AGGGUAUUAAGGUCGUGAAA6533
54790_2_11978−chr4: 105202003-105202023AAGGGUAUUAAGGUCGUGAA6534
54790_2_11982−chr4: 105202033-105202053GAUUCCGGAGGCCGACCCAC6535
54790_2_11983−chr4: 105202038-105202058CUAAAGAUUCCGGAGGCCGA6536
54790_2_11984−chr4: 105202039-105202059UCUAAAGAUUCCGGAGGCCG6537
54790_2_11987−chr4: 105202043-105202063GUAAUCUAAAGAUUCCGGAG6538
54790_2_11988−chr4: 105202044-105202064GGUAAUCUAAAGAUUCCGGA6539
54790_2_11989−chr4: 105202045-105202065UGGUAAUCUAAAGAUUCCGG6540
54790_2_11992−chr4: 105202048-105202068AGUUGGUAAUCUAAAGAUUC6541
54790_2_11995−chr4: 105202065-105202085AAAACCUGGAAGACAGAAGU6542
54790_2_12001−chr4: 105202079-105202099UUUCCAAGGACAUAAAAACC6543
54790_2_12003−chr4: 105202093-105202113AAAAUAUGCAUAAAUUUCCA6544
54790_2_12007−chr4: 105202127-105202147AUUAGGAAGAAGAUGAGGAU6545
54790_2_12008−chr4: 105202128-105202148GAUUAGGAAGAAGAUGAGGA6546
54790_2_12010−chr4: 105202132-105202152CAAGGAUUAGGAAGAAGAUG6547
54790_2_12016−chr4: 105202144-105202164UUCACAAUAUGUCAAGGAUU6548
54790_2_12019−chr4: 105202150-105202170UCUGUGUUCACAAUAUGUCA6549
54790_2_12027−chr4: 105202194-105202214UUAAGUAUAUUUGUAACUCA6550
54790_2_12029−chr4: 105202195-105202215UUUAAGUAUAUUUGUAACUC6551
54790_2_12058−chr4: 105202342-105202362GAGUCCGAAAAGUUUCCACU6552
54790_2_12059−chr4: 105202343-105202363CGAGUCCGAAAAGUUUCCAC6553
54790_2_12062−chr4: 105202348-105202368GUCUCCGAGUCCGAAAAGUU6554
54790_2_12063−chr4: 105202359-105202379UAGAGUGUAGAGUCUCCGAG6555
54790_2_12065−chr4: 105202365-105202385CGUCAGUAGAGUGUAGAGUC6556
54790_2_12075−chr4: 105202436-105202456CCUUCGCUGGAUCCUAAAUC6557
54790_2_12078−chr4: 105202445-105202465GUUCAUCACCCUUCGCUGGA6558
54790_2_12086−chr4: 105202457-105202477UUAGGGUAGUAUGUUCAUCA6559
54790_2_12087−chr4: 105202458-105202478UUUAGGGUAGUAUGUUCAUC6560
54790_2_12093−chr4: 105202474-105202494UGCGAAUUACAGAUUUUUUA6561
54790_2_12094−chr4: 105202475-105202495UUGCGAAUUACAGAUUUUUU6562
54790_2_12121−chr4: 105202623-105202643CCAAAAAAUGACUGCCUUUA6563
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54790_2_12133−chr4: 105202706-105202726AGGCAUAUGUUGCAAAAUGA6565
54790_2_12134−chr4: 105202707-105202727UAGGCAUAUGUUGCAAAAUG6566
54790_2_12137−chr4: 105202726-105202746GCAAGCCAGAUAUGAAAAGU6567
54790_2_12144−chr4: 105202748-105202768AUUAAAUUAUAAAUAAUAAA6568
54790_2_12149−chr4: 105202783-105202803UUACAAAACUAUGGAAAGAG6569
54790_2_12152−chr4: 105202792-105202812GCAAUUCUAUUACAAAACUA6570
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54790_2_12194−chr4: 105202978-105202998UUAAGACAUUUAAAAAUAUU6573
54790_2_12201−chr4: 105203058-105203078GUACACGGUUCGUGUCACAA6574
54790_2_12220−chr4: 105203175-105203195CUUACGUAAAAAUGUCUUAA6575
54790_2_12230−chr4: 105203222-105203242CUUAGUAAAGCAUAAUCAUA6576
54790_2_12232−chr4: 105203253-105203273CCACAUGGUCAAUGUAGGAA6577
54790_2_12234−chr4: 105203258-105203278UGAGUCCACAUGGUCAAUGU6578
54790_2_12237−chr4: 105203268-105203288AGGCCAAAUAUGAGUCCACA6579
54790_2_12245−chr4: 105203288-105203308UUAUUCUAAUGUAAUUAUAU6580
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54790_2_12302−chr4: 105203707-105203727UCUUGGUAUUACCUACCGUA6589
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54790_2_12327−chr4: 105203834-105203854UAAAUUUGCCUCGAAGAGUU6595
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54790_2_12384−chr4: 105204083-105204103GGAGUCGGAGGACUCAUCGA6613
54790_2_12385−chr4: 105204084-105204104CGGAGUCGGAGGACUCAUCG6614
54790_2_12392−chr4: 105204123-105204143AGUGACGUUGGAGCGGAGGG6615
54790_2_12393−chr4: 105204124-105204144GAGUGACGUUGGAGCGGAGG6616
54790_2_12396−chr4: 105204168-105204188AGAGUGAGGCAGCGGGUCCG6617
54790_2_12399−chr4: 105204172-105204192CCUCAGAGUGAGGCAGCGGG6618
54790_2_12413−chr4: 105204193-105204213AAACAAAAACAAAAAACUCU6619
54790_2_12428−chr4: 105204216-105204236CAAUAUAAAAAAAAAAAAAA6620
54790_2_12445−chr4: 105204334-105204354AUUCAAGAUUCUUGUCCUUG6621
54790_2_12449−chr4: 105204357-105204377UAAGUACCUCAUAUGCACUA6622
54790_2_12459−chr4: 105204413-105204433ACAUGAUGUCUAAUAUUUUU6623
54790_2_12465−chr4: 105204445-105204465AUACUUUUUCUAUCAACUGU6624
54790_2_12475−chr4: 105204488-105204508UUUGAAACAGUUUUCUCCAU6625
54790_2_12480−chr4: 105204512-105204532AUAUUUCGUUUCUUUUUCUU6626
54790_2_12482−chr4: 105204513-105204533AAUAUUUCGUUUCUUUUUCU6627
54790_2_12512−chr4: 105204681-105204701UGACGAUUUCAGUAGAGUUC6628
54790_2_12518−chr4: 105204712-105204732GAUCUCACGUACCACAAGGU6629
54790_2_12519−chr4: 105204713-105204733GGAUCUCACGUACCACAAGG6630
54790_2_12523−chr4: 105204722-105204742UAAUCUUUUGGAUCUCACGU6631
54790_2_12534−chr4: 105204808-105204828GUGAUUGAAUCACAUGUGUC6632
54790_2_12539−chr4: 105204851-105204871AGAUCACUUAUCGUUUUGAU6633
54790_2_12544−chr4: 105204881-105204901UUUAGAUUCUCAUCCAAGGA6634
54790_2_12547−chr4: 105204889-105204909CCGAAUUAUUUAGAUUCUCA6635
54790_2_12550−chr4: 105204910-105204930UUAUUGUUUUAUAUAUAUCA6636
54790_2_12561−chr4: 105204965-105204985UUCGUUUAAAUUCGUUUCUU6637
54790_2_12568−chr4: 105204994-105205014CAUAAGGUUUAGUGAUUAAA6638
54790_2_12578−chr4: 105205088-105205108UUCGUGGAGAGUUUUACGUA6639
54790_2_12586−chr4: 105205137-105205157CUUUCGUUUCGAAACUUUAU6640
54790_2_12607−chr4: 105205214-105205234AAAUAAUAAAGCUAGUCAAG6641
54790_2_12620−chr4: 105205298-105205318AAGUUAAGGAAAAUAUUGUU6642
54790_2_12622−chr4: 105205312-105205332AGGCUAAAAUUAAGAAGUUA6643
54790_2_12628−chr4: 105205332-105205352AAAUGAUUAACUUGGAAAAC6644
54790_2_12630−chr4: 105205340-105205360CAACAGAUAAAUGAUUAACU6645
54790_2_12640−chr4: 105205375-105205395CUGACAAAGAAAAUUUUCUU6646
54790_2_12660−chr4: 105205510-105205530UAGUACCUAUUGGGUUGGGG6647
54790_2_12662−chr4: 105205511-105205531AUAGUACCUAUUGGGUUGGG6648
54790_2_12663−chr4: 105205512-105205532AAUAGUACCUAUUGGGUUGG6649
54790_2_12665−chr4: 105205513-105205533GAAUAGUACCUAUUGGGUUG6650
54790_2_12667−chr4: 105205514-105205534AGAAUAGUACCUAUUGGGUU6651
54790_2_12670−chr4: 105205515-105205535CAGAAUAGUACCUAUUGGGU6652
54790_2_12672−chr4: 105205519-105205539AAAUCAGAAUAGUACCUAUU6653
54790_2_12673−chr4: 105205520-105205540CAAAUCAGAAUAGUACCUAU6654
54790_2_12680−chr4: 105205547-105205567UCCUUCAAGAAUGUGUGAAU6655
54790_2_12689−chr4: 105205587-105205607AAAUUAUAUUAUAAUUUUGU6656
54790_2_12690−chr4: 105205588-105205608AAAAUUAUAUUAUAAUUUUG6657
54790_2_12702−chr4: 105205674-105205694GACGGUAACGUGAGGUCGGA6658
54790_2_12707−chr4: 105205715-105205735GAGAACUUUGGCCCUCCGCC6659
54790_2_12708−chr4: 105205718-105205738UUAGAGAACUUUGGCCCUCC6660
54790_2_12711−chr4: 105205721-105205741CUCUUAGAGAACUUUGGCCC6661
54790_2_12713−chr4: 105205724-105205744GUCCUCUUAGAGAACUUUGG6662
54790_2_12714−chr4: 105205725-105205745CGUCCUCUUAGAGAACUUUG6663
54790_2_12720−chr4: 105205743-105205763CGAUGAGCCCUCCGACUCCG6664
54790_2_12722−chr4: 105205747-105205767GGGUCGAUGAGCCCUCCGAC6665
54790_2_12724−chr4: 105205753-105205773AUAUUAGGGUCGAUGAGCCC6666
54790_2_12726−chr4: 105205756-105205776CGGAUAUUAGGGUCGAUGAG6667
54790_2_12728−chr4: 105205757-105205777ACGGAUAUUAGGGUCGAUGA6668
54790_2_12731−chr4: 105205784-105205804UUUUUUAAUCGGUCCUCACC6669
54790_2_12732−chr4: 105205787-105205807UCUUUUUUUAAUCGGUCCUC6670
54790_2_12734−chr4: 105205792-105205812UUUUAUCUUUUUUUAAUCGG6671
54790_2_12740−chr4: 105205834-105205854ACUCUGGCCGGACUGGUUGU6672
54790_2_12744−chr4: 105205848-105205868ACUCCAACCCUCAAACUCUG6673
54790_2_12746−chr4: 105205861-105205881GUCCACCUAGUGGACUCCAA6674
54790_2_12749−chr4: 105205862-105205882CGUCCACCUAGUGGACUCCA6675
54790_2_12751−chr4: 105205866-105205886ACUUCGUCCACCUAGUGGAC6676
54790_2_12755−chr4: 105205877-105205897GAAAUCCUCCGACUUCGUCC6677
54790_2_12757−chr4: 105205880-105205900CGUGAAAUCCUCCGACUUCG6678
54790_2_12759−chr4: 105205890-105205910ACAUUAGGAUCGUGAAAUCC6679
54790_2_12760−chr4: 105205893-105205913CGGACAUUAGGAUCGUGAAA6680
54790_2_12766−chr4: 105205921-105205941AUGUUUUCCCGACCCACACC6681
54790_2_12768−chr4: 105205924-105205944AUAAUGUUUUCCCGACCCAC6682
54790_2_12769−chr4: 105205929-105205949UUAAGAUAAUGUUUUCCCGA6683
54790_2_12770−chr4: 105205930-105205950AUUAAGAUAAUGUUUUCCCG6684
54790_2_12772−chr4: 105205934-105205954CUCCAUUAAGAUAAUGUUUU6685
54790_2_12784−chr4: 105206023-105206043AAGGGUGUGGGUUGUGGGGU6686
54790_2_12785−chr4: 105206024-105206044AAAGGGUGUGGGUUGUGGGG6687
54790_2_12787−chr4: 105206027-105206047UACAAAGGGUGUGGGUUGUG6688
54790_2_12788−chr4: 105206028-105206048AUACAAAGGGUGUGGGUUGU6689
54790_2_12789−chr4: 105206029-105206049AAUACAAAGGGUGUGGGUUG6690
54790_2_12792−chr4: 105206035-105206055AAGAGAAAUACAAAGGGUGU6691
54790_2_12793−chr4: 105206036-105206056AAAGAGAAAUACAAAGGGUG6692
54790_2_12795−chr4: 105206041-105206061AAGUAAAAGAGAAAUACAAA6693
54790_2_12796−chr4: 105206042-105206062CAAGUAAAAGAGAAAUACAA6694
54790_2_12801−chr4: 105206071-105206091AAACUAUAAAUCUGAACUAG6695
54790_2_12807−chr4: 105206127-105206147GAGCUGUUCCCCAACCAGAU6696
54790_2_12808−chr4: 105206128-105206148AGAGCUGUUCCCCAACCAGA6697
54790_2_12811−chr4: 105206153-105206173GGAAAGGGAGAGGUCCCAGU6698
54790_2_12813−chr4: 105206154-105206174AGGAAAGGGAGAGGUCCCAG6699
54790_2_12815−chr4: 105206163-105206183UCACUCAUGAGGAAAGGGAG6700
54790_2_12818−chr4: 105206168-105206188UGGCGUCACUCAUGAGGAAA6701
54790_2_12819−chr4: 105206169-105206189CUGGCGUCACUCAUGAGGAA6702
54790_2_12822−chr4: 105206174-105206194GGACCCUGGCGUCACUCAUG6703
54790_2_12827−chr4: 105206188-105206208GCUUAUGGGCAGCAGGACCC6704
54790_2_12828−chr4: 105206195-105206215ACAGAAUGCUUAUGGGCAGC6705
54790_2_12830−chr4: 105206202-105206222UCAGCAAACAGAAUGCUUAU6706
54790_2_12831−chr4: 105206203-105206223CUCAGCAAACAGAAUGCUUA6707
54790_2_12834−chr4: 105206239-105206259AAGGCAGCGAAGCUGGGGAA6708
54790_2_12838−chr4: 105206244-105206264AGCCAAAGGCAGCGAAGCUG6709
54790_2_12840−chr4: 105206245-105206265CAGCCAAAGGCAGCGAAGCU6710
54790_2_12842−chr4: 105206246-105206266GCAGCCAAAGGCAGCGAAGC6711
54790_2_12847−chr4: 105206258-105206278CUUAAUCACAAAGCAGCCAA6712
54790_2_12850−chr4: 105206290-105206310AAGGAGGCUUUAGGAAACAU6713
54790_2_12851−chr4: 105206291-105206311GAAGGAGGCUUUAGGAAACA6714
54790_2_12853−chr4: 105206299-105206319CUAAAGGCGAAGGAGGCUUU6715
54790_2_12856−chr4: 105206306-105206326UCAAGGACUAAAGGCGAAGG6716
54790_2_12858−chr4: 105206309-105206329GCAUCAAGGACUAAAGGCGA6717
54790_2_12861−chr4: 105206315-105206335UCCCCAGCAUCAAGGACUAA6718
54790_2_12862−chr4: 105206323-105206343CCAAAAGGUCCCCAGCAUCA6719
54790_2_12865−chr4: 105206338-105206358AAGCUGUCUUCCCAACCAAA6720
54790_2_12867−chr4: 105206361-105206381AGCAGGCUCACCCUGACAUA6721
54790_2_12870−chr4: 105206378-105206398GAGUUACAUACCUGUGUAGC6722
54790_2_12872−chr4: 105206410-105206430CUAAACAGAAACUCAACAGU6723
54790_2_12879−chr4: 105206446-105206466UCCACGUUUGUACCAUUUGA6724
54790_2_12882−chr4: 105206447-105206467CUCCACGUUUGUACCAUUUG6725
54790_2_12887−chr4: 105206488-105206508AGACAAAACUAACAGGACAA6726
54790_2_12888−chr4: 105206495-105206515CUGUGAUAGACAAAACUAAC6727
54790_2_12893−chr4: 105206518-105206538AUCUCUUAUUUGGAGGGCAU6728
54790_2_12894−chr4: 105206519-105206539CAUCUCUUAUUUGGAGGGCA6729
54790_2_12896−chr4: 105206524-105206544UCCAUCAUCUCUUAUUUGGA6730
54790_2_12897−chr4: 105206525-105206545CUCCAUCAUCUCUUAUUUGG6731
54790_2_12900−chr4: 105206528-105206548CUGCUCCAUCAUCUCUUAUU6732
54790_2_12907−chr4: 105206573-105206593CCCUCUUUUAAAGUCAGUUG6733
54790_2_12922−chr4: 105206673-105206693UACCUUAUCACGGUCGACUC6734
54790_2_12927−chr4: 105206692-105206712GGUAAUCGUGAUUUUAUGGU6735
54790_2_12939−chr4: 105206796-105206816UGGAGGACUUGUAGACUAGC6736
54790_2_12942−chr4: 105206813-105206833CAUGAACAAAAUCAGGCUGG6737
54790_2_12944−chr4: 105206816-105206836GUUCAUGAACAAAAUCAGGC6738
54790_2_12948−chr4: 105206820-105206840UCAUGUUCAUGAACAAAAUC6739
54790_2_12958−chr4: 105206864-105206884AAAGCAGUAUCCAAUAUUAA6740
54790_2_12979−chr4: 105206941-105206961UAUUUUUGUUCUUGCGAGAC6741
54790_2_12986−chr4: 105206966-105206986CAAACUUGUUUUAUAUGACU6742
54790_2_13013−chr4: 105207076-105207096CAUUUCCAUAUAUUAAUGUU6743
54790_2_13027−chr4: 105207149-105207169GAGAAUCUUAUAAAAGCAAC6744
54790_2_13055−chr4: 105207308-105207328AAGGAGAGUUCUCAUGCUUA6745
54790_2_13061−chr4: 105207327-105207347GUCUCCCUUUGUACUUCAAA6746
54790_2_13080−chr4: 105207407-105207427AAUCUGUUGGCUAUUCUGAA6747
54790_2_13084−chr4: 105207420-105207440AACUCUUGUUUAAAAUCUGU6748
54790_2_13095−chr4: 105207515-105207535AUAGCCAAAACAAGCAGAAA6749
54790_2_13096−chr4: 105207516-105207536CAUAGCCAAAACAAGCAGAA6750
54790_2_13101−chr4: 105207543-105207563CUUAAAUACAGACACUGAAA6751
54790_2_13115−chr4: 105207613-105207633UUUCACAUCCGAAAUCAUAC6752
54790_2_13119−chr4: 105207651-105207671CACAGCAGUAUAGGUUAACA6753
54790_2_13122−chr4: 105207660-105207680AAUGACUUCCACAGCAGUAU6754
54790_2_13135−chr4: 105207734-105207754AAGAGUGAUAAAGUUAAAUU6755
54790_2_13146−chr4: 105207791-105207811AGAUAGAAGUUAUCGUCUGU6756
54790_2_13159−chr4: 105207870-105207890UCAAUGAAUUCUUCUUUGGU6757
54790_2_13165−chr4: 105207909-105207929AUAUGAGGGGUAACCACACU6758
54790_2_13166−chr4: 105207910-105207930GAUAUGAGGGGUAACCACAC6759
54790_2_13170−chr4: 105207917-105207937GACAGUAGAUAUGAGGGGUA6760
54790_2_13177−chr4: 105207964-105207984GUUUAAGUUGAAUAGGUUUU6761
54790_2_13180−chr4: 105207992-105208012AGACAUGGACAUACAGGGUA6762
54790_2_13189−chr4: 105208037-105208057GAAGUCGUCUCAAGUGUUAA6763
54790_2_13206−chr4: 105208147-105208167AGGUGACCCAAGAGAUGGCC6764
54790_2_13209−chr4: 105208152-105208172UGGCAAGGUGACCCAAGAGA6765
54790_2_13212−chr4: 105208167-105208187AAGAGAAUGAAAAGUUGGCA6766
54790_2_13213−chr4: 105208172-105208192UUGUAAAGAGAAUGAAAAGU6767
54790_2_13227−chr4: 105208233-105208253CAAGGUGACCCAAGAUAAGU6768
54790_2_13228−chr4: 105208251-105208271AAGAGAAUGAAAAGUUAGCA6769
54790_2_13237−chr4: 105208302-105208322GAGAAGCCAGCUUGAGAAUG6770
54790_2_13238−chr4: 105208303-105208323AGAGAAGCCAGCUUGAGAAU6771
54790_2_13240−chr4: 105208304-105208324CAGAGAAGCCAGCUUGAGAA6772
54790_2_13256−chr4: 105208367-105208387CUGCUCAAUGCUAGCCAUUU6773
54790_2_13257−chr4: 105208368-105208388CCUGCUCAAUGCUAGCCAUU6774
54790_2_13262−chr4: 105208394-105208414UAAUUCAGAGGAGUAUGUUG6775
54790_2_13263−chr4: 105208395-105208415GUAAUUCAGAGGAGUAUGUU6776
54790_2_13266−chr4: 105208396-105208416UGUAAUUCAGAGGAGUAUGU6777
54790_2_13268−chr4: 105208406-105208426UAACUCAAAAUGUAAUUCAG6778
54790_2_13286−chr4: 105208503-105208523UCUCUAUCCCUUAUACUUAA6779
54790_2_13297−chr4: 105208578-105208598AGAAGUAUAAACUGAUUAAA6780
54790_2_13305−chr4: 105208611-105208631CUCAGCAACUUUUUGAUGAC6781
54790_2_13320−chr4: 105208720-105208740UCCUAAACUUUGAGAUUAAU6782
54790_2_13328−chr4: 105208777-105208797AGGUUACCACGUCAAAAAGC6783
54790_2_13337−chr4: 105208797-105208817CUGUUUCCUUUUGUUAUGGC6784
54790_2_13340−chr4: 105208801-105208821CCUGCUGUUUCCUUUUGUUA6785
54790_2_13347−chr4: 105208834-105208854GGGAAGAAGACUGUUUUAAU6786
54790_2_13356−chr4: 105208854-105208874GCUGACAGUUCGUUCUUUGG6787
54790_2_13357−chr4: 105208855-105208875UGCUGACAGUUCGUUCUUUG6788
54790_2_13359−chr4: 105208856-105208876UUGCUGACAGUUCGUUCUUU6789
54790_2_13362−chr4: 105208857-105208877UUUGCUGACAGUUCGUUCUU6790
54790_2_13387−chr4: 105208977-105208997AAUGCCAAACUUAAUUCUAC6791
54790_2_13394−chr4: 105209039-105209059AUAUAUAUAUCCAUGCCUUG6792
54790_2_13407−chr4: 105209171-105209191GAAUACACACCAAAAGUGAA6793
54790_2_13411−chr4: 105209193-105209213CUGGUUGAAUAACUCACAGC6794
54790_2_13417−chr4: 105209212-105209232AGACUCAAACUUAGUGAGCC6795
54790_2_13442−chr4: 105209338-105209358AGAUUUCCUCCCUAUUUGGA6796
54790_2_13445−chr4: 105209342-105209362UUUCAGAUUUCCUCCCUAUU6797
54790_2_13449−chr4: 105209373-105209393CAGAGCAUCUCAGUCAACAC6798
54790_2_13453−chr4: 105209402-105209422AGUUGGUGAGCUCUGAGUCC6799
54790_2_13457−chr4: 105209419-105209439UUAACAUAAAGAUCCAAAGU6800
54790_2_13465−chr4: 105209489-105209509AGCCACUGACCUAUAUCAAG6801
54790_2_13475−chr4: 105209526-105209546UUUAGUUAAAAGAAAGUUGU6802
54790_2_13482−chr4: 105209561-105209581CCCAUUGUGACAAACCAACU6803
54790_2_13500−chr4: 105209668-105209688UUAUAAAAGCAUCUUCACCA6804
54790_2_13516−chr4: 105209730-105209750UGUUUAAAAUAAUUCUUUCA6805
54790_2_13533−chr4: 105209900-105209920ACGACAGUGGUAGAGUAACG6806
54790_2_13539−chr4: 105209927-105209947ACAGGAAUGAAAAUGAUGGU6807
54790_2_13550−chr4: 105209990-105210010GGCAAAUUUUUUAUUGGAUA6808
54790_2_13558−chr4: 105210031-105210051UCAAUGAAUUCUUCUUUGGU6809
54790_2_13564−chr4: 105210069-105210089UGUAAGGGGUAGUCACACUC6810
54790_2_13565−chr4: 105210070-105210090AUGUAAGGGGUAGUCACACU6811
54790_2_13566−chr4: 105210071-105210091GAUGUAAGGGGUAGUCACAC6812
54790_2_13576−chr4: 105210123-105210143GUUUGAGAUGAAUAGGUUUU6813
54790_2_13579−chr4: 105210151-105210171AGACAUGGACAUACAGGGUA6814
54790_2_13587−chr4: 105210196-105210216GAAGUCGUCUCAAGUGUUAA6815
54790_2_13602−chr4: 105210306-105210326UCCACUGGGUUCUCUACCGG6816
54790_2_13605−chr4: 105210311-105210331GUUGUUCCACUGGGUUCUCU6817
54790_2_13608−chr4: 105210326-105210346UUCUCUUACUUUUCAGUUGU6818
54790_2_13619−chr4: 105210379-105210399CUCUUCGGUCGGACUCUAAC6819
54790_2_13620−chr4: 105210380-105210400CCUCUUCGGUCGGACUCUAA6820
54790_2_13621−chr4: 105210381-105210401ACCUCUUCGGUCGGACUCUA6821
54790_2_13628−chr4: 105210401-105210421UAGGGUUCAUUCUCAUGUCA6822
54790_2_13635−chr4: 105210453-105210473CUUGACACAAUUGGAUGGUU6823
54790_2_13638−chr4: 105210486-105210506UUAGUCGUUCCCCAGAUUCG6824
54790_2_13641−chr4: 105210496-105210516GUUCAGUCCUUUAGUCGUUC6825
54790_2_13642−chr4: 105210497-105210517UGUUCAGUCCUUUAGUCGUU6826
54790_2_13643−chr4: 105210498-105210518AUGUUCAGUCCUUUAGUCGU6827
54790_2_13648−chr4: 105210510-105210530CCGUCAACUCACAUGUUCAG6828
54790_2_13653−chr4: 105210531-105210551AAUUUCACCCAUAUAAUCCG6829
54790_2_13655−chr4: 105210535-105210555UAGUAAUUUCACCCAUAUAA6830
54790_2_13657−chr4: 105210544-105210564UACAUGUAAUAGUAAUUUCA6831
54790_2_13659−chr4: 105210545-105210565CUACAUGUAAUAGUAAUUUC6832
54790_2_13667−chr4: 105210595-105210615AUACUGACUGUCUUUUUAAU6833
54790_2_13673−chr4: 105210623-105210643UAAACAAUCCUACCCAUUUA6834
54790_2_13674−chr4: 105210624-105210644AUAAACAAUCCUACCCAUUU6835
54790_2_13678−chr4: 105210631-105210651UACCACGAUAAACAAUCCUA6836
54790_2_13679−chr4: 105210632-105210652CUACCACGAUAAACAAUCCU6837
54790_2_13681−chr4: 105210636-105210656ACUACUACCACGAUAAACAA6838
54790_2_13686−chr4: 105210650-105210670AACUCGAUUUUCCAACUACU6839
54790_2_13688−chr4: 105210660-105210680CUCAAAACAGAACUCGAUUU6840
54790_2_13693−chr4: 105210705-105210725CUACACUCUUUCAUGUACUU6841
54790_2_13700−chr4: 105210732-105210752CUUUGUCUUGUUGAACCAUU6842
54790_2_13705−chr4: 105210738-105210758UUCCGUCUUUGUCUUGUUGA6843
54790_2_13711−chr4: 105210757-105210777UUUAAAUCCUGUGUAAAACU6844
54790_2_13713−chr4: 105210771-105210791CGUCUCUUUACCUAUUUAAA6845
54790_2_13715−chr4: 105210782-105210802CUUAUCGUCACCGUCUCUUU6846
54790_2_13719−chr4: 105210793-105210813GGACUUGAUCUCUUAUCGUC6847
54790_2_13724−chr4: 105210825-105210845UGGCGUCAUUAUGUUCUCUU6848
54790_2_13738−chr4: 105210903-105210923UCUGGAAAUUUUCUAGUGAG6849
54790_2_13744−chr4: 105210961-105210981AUUUAGGUCACCCUUCGGUA6850
54790_2_13748−chr4: 105210971-105210991CUAAUAAUAAAUUUAGGUCA6851
54790_2_13750−chr4: 105210972-105210992UCUAAUAAUAAAUUUAGGUC6852
54790_2_13752−chr4: 105211007-105211027CUUCAUACAUUUCCGGUACC6853
54790_2_13756−chr4: 105211010-105211030GAUCUUCAUACAUUUCCGGU6854
54790_2_13759−chr4: 105211016-105211036CACGCCGAUCUUCAUACAUU6855
54790_2_13764−chr4: 105211033-105211053UUCUCCUCACAAAACUCCAC6856
54790_2_13765−chr4: 105211038-105211058ACUUGUUCUCCUCACAAAAC6857
54790_2_13770−chr4: 105211050-105211070CAAUCAAGAGUCACUUGUUC6858
54790_2_13774−chr4: 105211077-105211097AUCGACUCCUCUUCUCUUUG6859
54790_2_13780−chr4: 105211091-105211111UUUAAUCGUACUAUAUCGAC6860
54790_2_13785−chr4: 105211125-105211145UCUCCCUUGUUUUCAUGUUU6861
54790_2_13787−chr4: 105211142-105211162CCUUCUUACUAAGUCGAUCU6862
54790_2_13789−chr4: 105211143-105211163ACCUUCUUACUAAGUCGAUC6863
54790_2_13794−chr4: 105211163-105211183UUCGGUUACUAUCUUACUGG6864
54790_2_13807−chr4: 105211230-105211250GAUAAAUCUAUCUCGUCCAU6865
54790_2_13809−chr4: 105211235-105211255GUCCUGAUAAAUCUAUCUCG6866
54790_2_13811−chr4: 105211254-105211274CUCUAUUUCUCCUGAUUUUG6867
54790_2_13813−chr4: 105211265-105211285UAGACUCACUACUCUAUUUC6868
54790_2_13821−chr4: 105211294-105211314GUCUGACUACUCACGAUACU6869
54790_2_13823−chr4: 105211295-105211315AGUCUGACUACUCACGAUAC6870
54790_2_13832−chr4: 105211375-105211395AUCCCUACUUGUUCUAUCAG6871
54790_2_13838−chr4: 105211393-105211413AAGAUCCAAGAUCCCUACAU6872
54790_2_13839−chr4: 105211394-105211414CAAGAUCCAAGAUCCCUACA6873
54790_2_13844−chr4: 105211401-105211421UGUAUAACAAGAUCCAAGAU6874
54790_2_13845−chr4: 105211402-105211422UUGUAUAACAAGAUCCAAGA6875
54790_2_13852−chr4: 105211409-105211429AUAGAAAUUGUAUAACAAGA6876
54790_2_13860−chr4: 105211472-105211492GUCACCUCAGGGGGCUGGAC6877
54790_2_13862−chr4: 105211477-105211497UGCUGGUCACCUCAGGGGGC6878
54790_2_13865−chr4: 105211481-105211501UAAAUGCUGGUCACCUCAGG6879
54790_2_13866−chr4: 105211482-105211502CUAAAUGCUGGUCACCUCAG6880
54790_2_13869−chr4: 105211483-105211503CCUAAAUGCUGGUCACCUCA6881
54790_2_13871−chr4: 105211484-105211504CCCUAAAUGCUGGUCACCUC6882
54790_2_13873−chr4: 105211494-105211514UCGGCUUAUUCCCUAAAUGC6883
54790_2_13876−chr4: 105211513-105211533UUAAUGGCCCUCCUCUGCCU6884
54790_2_13878−chr4: 105211529-105211549CUCUCAUUGCUCCUUCUUAA6885
54790_2_13888−chr4: 105211578-105211598GUUAGGACACUCUCACUUUA6886
54790_2_13890−chr4: 105211579-105211599UGUUAGGACACUCUCACUUU6887
54790_2_13896−chr4: 105211595-105211615CUUUCAUUUAGACCUGUGUU6888
54790_2_13913−chr4: 105211697-105211717CAGAAUUUCCCUAUCUUUCA6889
54790_2_13920−chr4: 105211769-105211789GGGAUGACUAUUCCCCAAAC6890
54790_2_13921−chr4: 105211789-105211809CUCUAUUGUGAAAGACAAAU6891
54790_2_13923−chr4: 105211790-105211810ACUCUAUUGUGAAAGACAAA6892
54790_2_13933−chr4: 105211833-105211853CACUGUUGUAAUUGUGAUUU6893
54790_2_13946−chr4: 105211876-105211896ACAAAUGACACACUAGGACU6894
54790_2_13956−chr4: 105211971-105211991GUGAAUAUGAGGUGGCCAUA6895
54790_2_13959−chr4: 105211979-105211999UAUGCAGGGUGAAUAUGAGG6896
54790_2_13960−chr4: 105211982-105212002UUAUAUGCAGGGUGAAUAUG6897
54790_2_13964−chr4: 105211993-105212013UUGGCAUACUGUUAUAUGCA6898
54790_2_13965−chr4: 105211994-105212014AUUGGCAUACUGUUAUAUGC6899
54790_2_13970−chr4: 105212012-105212032UUCACGCCUCAUUCCUACAU6900
54790_2_13978−chr4: 105212066-105212086AGCUACCAAAGGAAUAAUCA6901
54790_2_13981−chr4: 105212077-105212097AUUUCCCUUGAAGCUACCAA6902
54790_2_13990−chr4: 105212125-105212145GACAGAUAAAGUGCUGACAU6903
54790_2_13994−chr4: 105212126-105212146GGACAGAUAAAGUGCUGACA6904
54790_2_14000−chr4: 105212147-105212167UUUGGAAUUUCUCAUGUUUC6905
54790_2_14003−chr4: 105212165-105212185AACUGCAUGGCUUGAACAUU6906
54790_2_14007−chr4: 105212178-105212198CUGACUAGAUAAAAACUGCA6907
54790_2_14011−chr4: 105212214-105212234CAUUACAACUAUGGGUAACC6908
54790_2_14013−chr4: 105212222-105212242GAGGUAUUCAUUACAACUAU6909
54790_2_14014−chr4: 105212223-105212243GGAGGUAUUCAUUACAACUA6910
54790_2_14017−chr4: 105212241-105212261ACAUUAAGAAGAUAAAGAGG6911
54790_2_14018−chr4: 105212244-105212264AGAACAUUAAGAAGAUAAAG6912
54790_2_14030−chr4: 105212273-105212293AGUAAUCUUUAUAGAUCAUU6913
54790_2_14032−chr4: 105212303-105212323CUGCUGGACCUCAAUCUGAA6914
54790_2_14036−chr4: 105212319-105212339GUAGUGUUCUGAAAGUCUGC6915
54790_2_14048−chr4: 105212357-105212377AGCUUAUUAUUUUAUUAGUU6916
54790_2_14049−chr4: 105212358-105212378GAGCUUAUUAUUUUAUUAGU6917
54790_2_14061−chr4: 105212474-105212494CCACAAAUAAAGGCAAAUAC6918
54790_2_14062−chr4: 105212484-105212504GUGUGUAUACCCACAAAUAA6919
54790_2_14068−chr4: 105212518-105212538AAUGAUUUUACUCUAGUUUA6920
54790_2_14078−chr4: 105212568-105212588AUACACAAUUUGAAAAUUUU6921
54790_2_14080−chr4: 105212569-105212589CAUACACAAUUUGAAAAUUU6922
54790_2_14092−chr4: 105212617-105212637UAAUUUCAUUUAAACCAGAA6923
54790_2_14108−chr4: 105212708-105212728GCACUCGAUGGCGUGGACCG6924
54790_2_14111−chr4: 105212712-105212732GUCCGCACUCGAUGGCGUGG6925
54790_2_14113−chr4: 105212731-105212751AGGGUUUCACGACCCUAAUG6926
54790_2_14114−chr4: 105212739-105212759GGAGUCGGAGGGUUUCACGA6927
54790_2_14115−chr4: 105212740-105212760CGGAGUCGGAGGGUUUCACG6928
54790_2_14122−chr4: 105212773-105212793CCAAAACUUGAGGACUGAAG6929
54790_2_14127−chr4: 105212794-105212814AAAGUGGUACAACCGGUCCG6930
54790_2_14128−chr4: 105212798-105212818UCCCAAAGUGGUACAACCGG6931
54790_2_14129−chr4: 105212803-105212823CUCUGUCCCAAAGUGGUACA6932
54790_2_14138−chr4: 105212817-105212837AACAUAAAAAUCAUCUCUGU6933
54790_2_14139−chr4: 105212818-105212838AAACAUAAAAAUCAUCUCUG6934
54790_2_14142−chr4: 105212847-105212867GUCCGUGCACGGUGGUACGG6935
54790_2_14143−chr4: 105212866-105212886UAGGUUCAUAGACCCUGAUG6936
54790_2_14144−chr4: 105212874-105212894GGAGUCGGUAGGUUCAUAGA6937
54790_2_14145−chr4: 105212875-105212895CGGAGUCGGUAGGUUCAUAG6938
54790_2_14150−chr4: 105212914-105212934GUGACGUUGGAGGCGGAGGA6939
54790_2_14151−chr4: 105212915-105212935AGUGACGUUGGAGGCGGAGG6940
54790_2_14153−chr4: 105212950-105212970AGCUGGUCCGAUCUCACGUC6941
54790_2_14156−chr4: 105212964-105212984UCUAAGAGUGAGACAGCUGG6942
54790_2_14173−chr4: 105213016-105213036GGUGGGUGGGUGGGGGAAUG6943
54790_2_14174−chr4: 105213017-105213037UGGUGGGUGGGUGGGGGAAU6944
54790_2_14177−chr4: 105213018-105213038UUGGUGGGUGGGUGGGGGAA6945
54790_2_14180−chr4: 105213023-105213043GUCUUUUGGUGGGUGGGUGG6946
54790_2_14181−chr4: 105213024-105213044AGUCUUUUGGUGGGUGGGUG6947
54790_2_14183−chr4: 105213025-105213045GAGUCUUUUGGUGGGUGGGU6948
54790_2_14186−chr4: 105213026-105213046GGAGUCUUUUGGUGGGUGGG6949
54790_2_14188−chr4: 105213029-105213049AAUGGAGUCUUUUGGUGGGU6950
54790_2_14189−chr4: 105213030-105213050CAAUGGAGUCUUUUGGUGGG6951
54790_2_14191−chr4: 105213033-105213053CUCCAAUGGAGUCUUUUGGU6952
54790_2_14192−chr4: 105213034-105213054ACUCCAAUGGAGUCUUUUGG6953
54790_2_14194−chr4: 105213037-105213057AAAACUCCAAUGGAGUCUUU6954
54790_2_14198−chr4: 105213047-105213067UUUGUAAAAUAAAACUCCAA6955
54790_2_14214−chr4: 105213139-105213159CUAUGUCAGAAAAAGAAUUG6956
54790_2_14230−chr4: 105213245-105213265CUGACGUGUCAAACUUCAGC6957
54790_2_14262−chr4: 105213379-105213399AAACUCAAUUUGAUUAAAAU6958
54790_2_14274−chr4: 105213451-105213471UUAGUGUGUCAUUUUGAAUA6959
54790_2_14278−chr4: 105213480-105213500CAAUGAGAAGAAUACAGAUG6960
54790_2_14285−chr4: 105213519-105213539AAGUCCAUUUGGUCAAGCAU6961
54790_2_14287−chr4: 105213530-105213550AAAAUAGCAGGAAGUCCAUU6962
54790_2_14289−chr4: 105213542-105213562GAAAAAUAUCUUAAAAUAGC6963
54790_2_14299−chr4: 105213603-105213623AGAAGAACAUCCUAGGUAAA6964
54790_2_14302−chr4: 105213604-105213624AAGAAGAACAUCCUAGGUAA6965
54790_2_14305−chr4: 105213610-105213630CAGUGAAAGAAGAACAUCCU6966
54790_2_14323−chr4: 105213656-105213676GGCUUUUGGUAGUGUGCUUU6967
54790_2_14325−chr4: 105213670-105213690UCAUCCAAAUGAAGGGCUUU6968
54790_2_14326−chr4: 105213677-105213697AGGUGGGUCAUCCAAAUGAA6969
54790_2_14327−chr4: 105213678-105213698AAGGUGGGUCAUCCAAAUGA6970
54790_2_14330−chr4: 105213693-105213713AUGGAGACUCAUAGGAAGGU6971
54790_2_14331−chr4: 105213694-105213714UAUGGAGACUCAUAGGAAGG6972
54790_2_14333−chr4: 105213697-105213717AACUAUGGAGACUCAUAGGA6973
54790_2_14335−chr4: 105213701-105213721AUGCAACUAUGGAGACUCAU6974
54790_2_14338−chr4: 105213712-105213732UGCCAUCAGACAUGCAACUA6975
54790_2_14353−chr4: 105213795-105213815AUGGGAAACAGAAUGACAAU6976
54790_2_14356−chr4: 105213813-105213833AGUACUGUACUAGGUGCCAU6977
54790_2_14358−chr4: 105213814-105213834GAGUACUGUACUAGGUGCCA6978
54790_2_14360−chr4: 105213822-105213842UGUGAGCAGAGUACUGUACU6979
54790_2_14369−chr4: 105213892-105213912UGAGGUGGGACCCGCUGUCU6980
54790_2_14371−chr4: 105213893-105213913AUGAGGUGGGACCCGCUGUC6981
54790_2_14375−chr4: 105213902-105213922CGUGGUGACAUGAGGUGGGA6982
54790_2_14376−chr4: 105213903-105213923ACGUGGUGACAUGAGGUGGG6983
54790_2_14382−chr4: 105213943-105213963AGUGAACUUGGGUCGUCGUC6984
54790_2_14386−chr4: 105213970-105213990CGAUGAGCCCUCAGACUCUG6985
54790_2_14390−chr4: 105213983-105214003ACCAUAUCAGGGUCGAUGAG6986
54790_2_14392−chr4: 105213984-105214004CACCAUAUCAGGGUCGAUGA6987
54790_2_14396−chr4: 105214003-105214023UCGGUCCGUACCACCGUACC6988
54790_2_14397−chr4: 105214006-105214026CAAUCGGUCCGUACCACCGU6989
54790_2_14399−chr4: 105214011-105214031AUUUUCAAUCGGUCCGUACC6990
54790_2_14401−chr4: 105214014-105214034AUGAUUUUCAAUCGGUCCGU6991
54790_2_14403−chr4: 105214019-105214039CAAAGAUGAUUUUCAAUCGG6992
54790_2_14406−chr4: 105214051-105214071CCUCUGGUCGGACCGGUUGU6993
54790_2_14407−chr4: 105214060-105214080GGUCCUCAACCUCUGGUCGG6994
54790_2_14410−chr4: 105214072-105214092CUAGUGAACUCCGGUCCUCA6995
54790_2_14412−chr4: 105214078-105214098GUCCACCUAGUGAACUCCGG6996
54790_2_14415−chr4: 105214083-105214103GUUCCGUCCACCUAGUGAAC6997
54790_2_14419−chr4: 105214094-105214114GAAAUACUCCGGUUCCGUCC6998
54790_2_14421−chr4: 105214097-105214117CGUGAAAUACUCCGGUUCCG6999
54790_2_14425−chr4: 105214101-105214121GGAUCGUGAAAUACUCCGGU7000
54790_2_14426−chr4: 105214107-105214127UUUUGAGGAUCGUGAAAUAC7001
54790_2_14428−chr4: 105214135-105214155AUAUAUAGCAUUGUACUGUA7002
54790_2_14430−chr4: 105214169-105214189CUCGAUACUUGGUCUUUGGU7003
54790_2_14435−chr4: 105214191-105214211UUCUGACAUUUUUCCCUAUA7004
54790_2_14438−chr4: 105214198-105214218GAUUGUUUUCUGACAUUUUU7005
54790_2_14439−chr4: 105214199-105214219AGAUUGUUUUCUGACAUUUU7006
54790_2_14446−chr4: 105214239-105214259CAAAAGAUUCCGGACGGGGC7007
54790_2_14448−chr4: 105214251-105214271UCCUCUCUAAGACAAAAGAU7008
54790_2_14451−chr4: 105214271-105214291CCCUGUUCACUUUCCUUCCG7009
54790_2_14453−chr4: 105214275-105214295AGCCCCCUGUUCACUUUCCU7010
54790_2_14454−chr4: 105214279-105214299AGGGAGCCCCCUGUUCACUU7011
54790_2_14458−chr4: 105214291-105214311UUUUUUUUUUAGAGGGAGCC7012
54790_2_14460−chr4: 105214292-105214312UUUUUUUUUUUAGAGGGAGC7013
54790_2_14461−chr4: 105214293-105214313UUUUUUUUUUUUAGAGGGAG7014
54790_2_14463−chr4: 105214294-105214314UUUUUUUUUUUUUAGAGGGA7015
54790_2_14467−chr4: 105214339-105214359UGAGGUCGGACCCACUGUGU7016
54790_2_14470−chr4: 105214340-105214360GUGAGGUCGGACCCACUGUG7017
54790_2_14472−chr4: 105214349-105214369UGUGGUGACGUGAGGUCGGA7018
54790_2_14473−chr4: 105214350-105214370GUGUGGUGACGUGAGGUCGG7019
54790_2_14477−chr4: 105214384-105214404UUGGAUCCUCCGACUCCGAC7020
54790_2_14479−chr4: 105214390-105214410ACGAACUUGGAUCCUCCGAC7021
54790_2_14481−chr4: 105214396-105214416CUCCUAACGAACUUGGAUCC7022
54790_2_14482−chr4: 105214399-105214419ACCCUCCUAACGAACUUGGA7023
54790_2_14487−chr4: 105214415-105214435UGAACCCUCCGACUCUACCC7024
54790_2_14489−chr4: 105214418-105214438CCAUGAACCCUCCGACUCUA7025
54790_2_14492−chr4: 105214419-105214439UCCAUGAACCCUCCGACUCU7026
54790_2_14495−chr4: 105214428-105214448ACAUCAGGGUCCAUGAACCC7027
54790_2_14496−chr4: 105214431-105214451CGGACAUCAGGGUCCAUGAA7028
54790_2_14498−chr4: 105214432-105214452ACGGACAUCAGGGUCCAUGA7029
54790_2_14501−chr4: 105214439-105214459ACCGUACACGGACAUCAGGG7030
54790_2_14502−chr4: 105214459-105214479UUUUUUUUACGGUCCACACC7031
54790_2_14503−chr4: 105214462-105214482UUUUUUUUUUUACGGUCCAC7032
54790_2_14504−chr4: 105214467-105214487UUUUUUUUUUUUUUUUACGG7033
54790_2_14506−chr4: 105214511-105214531CCUCCGGUCUGACCCGUUGU7034
54790_2_14507−chr4: 105214519-105214539GUCCUCGACCUCCGGUCUGA7035
54790_2_14509−chr4: 105214520-105214540GGUCCUCGACCUCCGGUCUG7036
54790_2_14511−chr4: 105214529-105214549GUGAACUCGGGUCCUCGACC7037
54790_2_14513−chr4: 105214532-105214552CUAGUGAACUCGGGUCCUCG7038
54790_2_14516−chr4: 105214538-105214558ACCCACCUAGUGAACUCGGG7039
54790_2_14521−chr4: 105214554-105214574CACCAAACUCGGUUCCACCC7040
54790_2_14524−chr4: 105214557-105214577CACCACCAAACUCGGUUCCA7041
54790_2_14525−chr4: 105214558-105214578ACACCACCAAACUCGGUUCC7042
54790_2_14527−chr4: 105214561-105214581CCCACACCACCAAACUCGGU7043
54790_2_14529−chr4: 105214573-105214593AGGGAGUCCCAACCCACACC7044
54790_2_14531−chr4: 105214576-105214596UAGAGGGAGUCCCAACCCAC7045
54790_2_14532−chr4: 105214581-105214601AAUCUUAGAGGGAGUCCCAA7046
54790_2_14533−chr4: 105214582-105214602UAAUCUUAGAGGGAGUCCCA7047
54790_2_14535−chr4: 105214586-105214606CUUCUAAUCUUAGAGGGAGU7048
54790_2_14536−chr4: 105214587-105214607CCUUCUAAUCUUAGAGGGAG7049
54790_2_14542−chr4: 105214608-105214628CUGAGUUUUAGUCUUCCCAC7050
54790_2_14544−chr4: 105214609-105214629UCUGAGUUUUAGUCUUCCCA7051
54790_2_14547−chr4: 105214610-105214630UUCUGAGUUUUAGUCUUCCC7052
54790_2_14549−chr4: 105214613-105214633AAAUUCUGAGUUUUAGUCUU7053
54790_2_14550−chr4: 105214614-105214634AAAAUUCUGAGUUUUAGUCU7054
54790_2_14555−chr4: 105214637-105214657UUUCCCACCCUGGAAGAGAC7055
54790_2_14556−chr4: 105214638-105214658GUUUCCCACCCUGGAAGAGA7056
54790_2_14557−chr4: 105214639-105214659CGUUUCCCACCCUGGAAGAG7057
54790_2_14563−chr4: 105214650-105214670GAAAGGGGUCACGUUUCCCA7058
54790_2_14564−chr4: 105214651-105214671GGAAAGGGGUCACGUUUCCC7059
54790_2_14567−chr4: 105214654-105214674UAAGGAAAGGGGUCACGUUU7060
54790_2_14568−chr4: 105214655-105214675GUAAGGAAAGGGGUCACGUU7061
54790_2_14575−chr4: 105214693-105214713UAGGAGGACUCAAAAAUACC7062
54790_2_14576−chr4: 105214696-105214716AGUUAGGAGGACUCAAAAAU7063
54790_2_14584−chr4: 105214745-105214765GUGGAAGGUCCUUGGAGGUG7064
54790_2_14585−chr4: 105214757-105214777GGGACCUACUCGGUGGAAGG7065
54790_2_14590−chr4: 105214774-105214794GCCUCGAAGAUUCAGGAGGG7066
54790_2_14593−chr4: 105214794-105214814ACUUCAUAUUCCUUUCACGU7067
54790_2_14597−chr4: 105214805-105214825CUACGAAUCCCACUUCAUAU7068
54790_2_14600−chr4: 105214817-105214837AUGUCUACUUCUCUACGAAU7069
54790_2_14601−chr4: 105214818-105214838UAUGUCUACUUCUCUACGAA7070
54790_2_14611−chr4: 105214841-105214861AUAUAAACGACCAAAUAGUU7071
54790_2_14613−chr4: 105214852-105214872UUUGUGAAUGAAUAUAAACG7072
54790_2_14620−chr4: 105214898-105214918GAGAAACCCAAGUUAUGCAA7073
54790_2_14623−chr4: 105214912-105214932CAAGGGUGUUGUGGGAGAAA7074
54790_2_14624−chr4: 105214913-105214933CCAAGGGUGUUGUGGGAGAA7075
54790_2_14628−chr4: 105214934-105214954CUGGUUGGUCGAAGCUCAAC7076
54790_2_14629−chr4: 105214935-105214955ACUGGUUGGUCGAAGCUCAA7077
54790_2_14630−chr4: 105214936-105214956GACUGGUUGGUCGAAGCUCA7078
54790_2_14636−chr4: 105214971-105214991GUCUGUGUUCAGUGUUUAGG7079
54790_2_14643−chr4: 105215048-105215068CACAGGAGGUUAAAUUAAGG7080
54790_2_14645−chr4: 105215070-105215090UGUUCGUCGUCUGUGAUCGA7081
54790_2_14646−chr4: 105215071-105215091UUGUUCGUCGUCUGUGAUCG7082
54790_2_14652−chr4: 105215106-105215126AGAACACUGGUUUACACACU7083
54790_2_14653−chr4: 105215107-105215127GAGAACACUGGUUUACACAC7084
54790_2_14664−chr4: 105215200-105215220AUCACUGCCUAUGGCACACA7085
54790_2_14667−chr4: 105215209-105215229CAUAUUCUUAUCACUGCCUA7086
54790_2_14671−chr4: 105215242-105215262AGGUCUCAUGUAGCAUUUUC7087
54790_2_14679−chr4: 105215262-105215282GAAAAUUAGAUUUUAUAAAA7088
54790_2_14701−chr4: 105215367-105215387UUUUCUAGAACAUUAUUUCA7089
54790_2_14713−chr4: 105215439-105215459GAAUAAUAAUUCAGGCUUUU7090
54790_2_14715−chr4: 105215447-105215467AAUGUGCUGAAUAAUAAUUC7091
54790_2_14733−chr4: 105215544-105215564CUCAGAGGCAUUUCUAACUC7092
54790_2_14737−chr4: 105215559-105215579AACUCUAAAUCUUUUCUCAG7093
54790_2_14753−chr4: 105215628-105215648UGCAUUAUUGAAGCAGUGCU7094
54790_2_14754−chr4: 105215629-105215649CUGCAUUAUUGAAGCAGUGC7095
54790_2_14764−chr4: 105215699-105215719GAUAAGGGGGAAAAAAAAAC7096
54790_2_14765−chr4: 105215712-105215732UAAAAUCACUGCAGAUAAGG7097
54790_2_14768−chr4: 105215713-105215733GUAAAAUCACUGCAGAUAAG7098
54790_2_14769−chr4: 105215714-105215734GGUAAAAUCACUGCAGAUAA7099
54790_2_14771−chr4: 105215715-105215735UGGUAAAAUCACUGCAGAUA7100
54790_2_14775−chr4: 105215735-105215755UAAGAUGUAGCAUGAAGAGA7101
54790_2_14783−chr4: 105215758-105215778AUGUUUCAAUGUUCUCUUUG7102
54790_2_14789−chr4: 105215806-105215826CCAGAAAUGAGUUGGCAUUC7103
54790_2_14792−chr4: 105215814-105215834UUAGAACCCCAGAAAUGAGU7104
54790_2_14798−chr4: 105215838-105215858UGCUCUGCUAAAAAAGGUUA7105
54790_2_14800−chr4: 105215844-105215864CUACACUGCUCUGCUAAAAA7106
54790_2_14804−chr4: 105215882-105215902UUACUCAGGCCGACCAUUUA7107
54790_2_14808−chr4: 105215896-105215916UUACAGUUAAAAUGUUACUC7108
54790_2_14811−chr4: 105215926-105215946UGUCAGACAUGUCUCUUCAA7109
54790_2_14819−chr4: 105215968-105215988AAAGGUACUUUAGUCACACA7110
54790_2_14823−chr4: 105215986-105216006GGUUGAUCUCUUAAUAGAAA7111
54790_2_14825−chr4: 105216007-105216027CAAAGAGUAGAAGGAAAUGG7112
54790_2_14826−chr4: 105216010-105216030GAACAAAGAGUAGAAGGAAA7113
54790_2_14829−chr4: 105216016-105216036AGGGGAGAACAAAGAGUAGA7114
54790_2_14840−chr4: 105216034-105216054CUGAAUUAACUUUAUUUAAG7115
54790_2_14844−chr4: 105216035-105216055GCUGAAUUAACUUUAUUUAA7116
54790_2_14847−chr4: 105216036-105216056AGCUGAAUUAACUUUAUUUA7117
54790_2_14860−chr4: 105216121-105216141UAGCUCUAAUAUUCACAGCA7118
54790_2_14875−chr4: 105216220-105216240UCCUUUUGUUUUAGUCAGCG7119
54790_2_14918−chr4: 105216500-105216520CUCUAUCGUAUCCAUCUUUU7120
54790_2_14938−chr4: 105216637-105216657AAAUGUUCUGCUUUAACCUG7121
54790_2_14941−chr4: 105216671-105216691GAUUGUAGAGGAAAACAUCU7122
54790_2_14943−chr4: 105216683-105216703GAACAAAAACAGGAUUGUAG7123
54790_2_14951−chr4: 105216693-105216713AUUUUUCAUAGAACAAAAAC7124
54790_2_14959−chr4: 105216717-105216737UAGUGAAUGAUCCAAGUUUA7125
54790_2_14985−chr4: 105216897-105216917AUAUAACCUUAACAUUACCU7126
54790_2_14998−chr4: 105217005-105217025CUCAAAAAAUCUAAACAUUU7127
54790_2_15007−chr4: 105217064-105217084UUCAUAGAGAAUGCAGGGAG7128
54790_2_15008−chr4: 105217065-105217085CUUCAUAGAGAAUGCAGGGA7129
54790_2_15009−chr4: 105217066-105217086UCUUCAUAGAGAAUGCAGGG7130
54790_2_15013−chr4: 105217069-105217089GUAUCUUCAUAGAGAAUGCA7131
54790_2_15015−chr4: 105217070-105217090UGUAUCUUCAUAGAGAAUGC7132
54790_2_15029−chr4: 105217127-105217147UCUGUUCAUAGGAUAUAAUU7133
54790_2_15030−chr4: 105217138-105217158GAAGAGAAAGGUCUGUUCAU7134
54790_2_15035−chr4: 105217150-105217170UGCCUUUGAAAUGAAGAGAA7135
54790_2_15073−chr4: 105217346-105217366GAGUUCAUUUUCAAGAGCAA7136
54790_2_15081−chr4: 105217408-105217428CUGAUGAGAACCUGUGGACU7137
54790_2_15084−chr4: 105217414-105217434GAGGCACUGAUGAGAACCUG7138
54790_2_15092−chr4: 105217433-105217453UAAUCUGUGCAUAGAUCUUG7139
54790_2_15101−chr4: 105217499-105217519AAGGUACCUUAUCGUAUGAA7140
54790_2_15103−chr4: 105217514-105217534GACUUAUUUGUCAUAAAGGU7141
54790_2_15111−chr4: 105217543-105217563UUUGUGUCCUAGUAACAAAU7142
54790_2_15115−chr4: 105217557-105217577AGGACCUGUAUUACUUUGUG7143
54790_2_15118−chr4: 105217574-105217594UCCACGACACACCGUAAAGG7144
54790_2_15120−chr4: 105217584-105217604UACAGACCUUUCCACGACAC7145
54790_2_15121−chr4: 105217594-105217614ACUACUAUCCUACAGACCUU7146
54790_2_15125−chr4: 105217599-105217619AUUAUACUACUAUCCUACAG7147
54790_2_15127−chr4: 105217607-105217627UUUCAGAAAUUAUACUACUA7148
54790_2_15135−chr4: 105217634-105217654UUAAAACAAAGAAAUUACGU7149
54790_2_15155−chr4: 105217720-105217740UUAACGUGUAAUUUUAAAAA7150
54790_2_15160−chr4: 105217746-105217766AUCUAUGGGACUGGUUCUUU7151
54790_2_15162−chr4: 105217747-105217767UAUCUAUGGGACUGGUUCUU7152
54790_2_15164−chr4: 105217755-105217775GUGAUAUCUAUCUAUGGGAC7153
54790_2_15166−chr4: 105217760-105217780CAUAUGUGAUAUCUAUCUAU7154
54790_2_15167−chr4: 105217761-105217781UCAUAUGUGAUAUCUAUCUA7155
54790_2_15174−chr4: 105217829-105217849AGAGAUGUGUCCUAAUGUGU7156
54790_2_15182−chr4: 105217922-105217942UUCUUCGUCCAGGAUCCGUU7157
54790_2_15187−chr4: 105217928-105217948CUGUAAUUCUUCGUCCAGGA7158
54790_2_15190−chr4: 105217935-105217955UUAAAAACUGUAAUUCUUCG7159
54790_2_15195−chr4: 105217964-105217984AGACGCCCUCUCUAUUUUAA7160
54790_2_15196−chr4: 105217965-105217985GAGACGCCCUCUCUAUUUUA7161
54790_2_15203−chr4: 105217979-105217999AAGUGAGCUCAGUUGAGACG7162
54790_2_15204−chr4: 105217980-105218000GAAGUGAGCUCAGUUGAGAC7163
54790_2_15230−chr4: 105218117-105218137AAAGCAAGUACCCUGGACAG7164
54790_2_15232−chr4: 105218124-105218144UGCCCUUAAAGCAAGUACCC7165
54790_2_15236−chr4: 105218147-105218167CUUCAUCUUCAAGAAUCACU7166
54790_2_15237−chr4: 105218148-105218168UCUUCAUCUUCAAGAAUCAC7167
54790_2_15247−chr4: 105218196-105218216UUAAAAAGCUUUCUUCAUUG7168
54790_2_15251−chr4: 105218223-105218243CAUAAAUUCUUCUAUGGGGC7169
54790_2_15253−chr4: 105218227-105218247GGAACAUAAAUUCUUCUAUG7170
54790_2_15254−chr4: 105218228-105218248AGGAACAUAAAUUCUUCUAU7171
54790_2_15255−chr4: 105218229-105218249UAGGAACAUAAAUUCUUCUA7172
54790_2_15260−chr4: 105218248-105218268GCCAAUAUGAUCACAUCACU7173
54790_2_15263−chr4: 105218270-105218290UUGGAAAAGAAACACUGGAU7174
54790_2_15264−chr4: 105218275-105218295UGUCCUUGGAAAAGAAACAC7175
54790_2_15268−chr4: 105218289-105218309CUCCUUAUCAGUACUGUCCU7176
54790_2_15274−chr4: 105218314-105218334UCAGGACAAAGAGGUAGAUU7177
54790_2_15275−chr4: 105218323-105218343AUGAUCUGUUCAGGACAAAG7178
54790_2_15277−chr4: 105218332-105218352UAGAUGGAGAUGAUCUGUUC7179
54790_2_15280−chr4: 105218348-105218368UGAGCCAAACUAUGAAUAGA7180
54790_2_15289−chr4: 105218407-105218427GGCAUGGCAUAGCCGACAUG7181
54790_2_15292−chr4: 105218423-105218443GCUAAAAGAACGAAACGGCA7182
54790_2_15293−chr4: 105218428-105218448AACAAGCUAAAAGAACGAAA7183
54790_2_15308−chr4: 105218482-105218502AAGACCACUUUCGGUUUGAA7184
54790_2_15309−chr4: 105218483-105218503GAAGACCACUUUCGGUUUGA7185
54790_2_15312−chr4: 105218491-105218511CUCAUCACGAAGACCACUUU7186
54790_2_15316−chr4: 105218528-105218548GCAAUGAUAAAUAUCUACUG7187
54790_2_15317−chr4: 105218529-105218549GGCAAUGAUAAAUAUCUACU7188
54790_2_15318−chr4: 105218530-105218550UGGCAAUGAUAAAUAUCUAC7189
54790_2_15322−chr4: 105218550-105218570UACGAUACUAAGAGAUUAAC7190
54790_2_15326−chr4: 105218590-105218610UUACUUGUACUAAUGUAGAU7191
54790_2_15334−chr4: 105218613-105218633AAUUUUUAAAUAUUAUGCUC7192
54790_2_15336−chr4: 105218614-105218634AAAUUUUUAAAUAUUAUGCU7193
54790_2_15338−chr4: 105218615-105218635AAAAUUUUUAAAUAUUAUGC7194
54790_2_15349−chr4: 105218673-105218693UGAGUUUUGGUUGAUUUACA7195
54790_2_15350−chr4: 105218674-105218694CUGAGUUUUGGUUGAUUUAC7196
54790_2_15352−chr4: 105218686-105218706AGAACAAGAAUGCUGAGUUU7197
54790_2_15357−chr4: 105218723-105218743AAGACAAGACAUAUACCUAC7198
54790_2_15371−chr4: 105218782-105218802UCCAGAAGUUGCAUAAAAUA7199
54790_2_15378−chr4: 105218806-105218826CUUCUGGAAACAUAAUUUAU7200
54790_2_15379−chr4: 105218807-105218827UCUUCUGGAAACAUAAUUUA7201
54790_2_15389−chr4: 105218822-105218842UUCAUUACAAAAGGUUCUUC7202
54790_2_15392−chr4: 105218831-105218851UAUAUAUUUUUCAUUACAAA7203
54790_2_15401−chr4: 105218932-105218952UCUGAAAAGCUCUGAUAAAU7204
54790_2_15433−chr4: 105219187-105219207AUCUUCUUAAAGAUUAAUAA7205
54790_2_15451−chr4: 105219233-105219253AGUUAAUUUGUAGGAUAUUA7206
54790_2_15452−chr4: 105219242-105219262UCAUGUUUUAGUUAAUUUGU7207
54790_2_15464−chr4: 105219280-105219300CAUUUUUAUUCUUCCUAUUU7208
54790_2_15467−chr4: 105219304-105219324AACUGGUUACCAUAACAAUC7209
54790_2_15471−chr4: 105219321-105219341UUGAUCUAGUCUUAAUCAAC7210
54790_2_15485−chr4: 105219382-105219402AAGGCAUGCCAUCUAUGUUU7211
54790_2_15493−chr4: 105219401-105219421UUCCCUACCAUUGCCUCAAA7212
54790_2_15500−chr4: 105219478-105219498UCCUUGUAACACAAGCAUUU7213
54790_2_15506−chr4: 105219503-105219523UUAUUUAAAAACUCUGUACC7214
54790_2_15512−chr4: 105219570-105219590CUAAAUUGUCACAUCCCCAG7215
54790_2_15513−chr4: 105219571-105219591ACUAAAUUGUCACAUCCCCA7216
54790_2_15517−chr4: 105219572-105219592AACUAAAUUGUCACAUCCCC7217
54790_2_15521−chr4: 105219597-105219617GAAAUUAACUAUAUUAGAGU7218
54790_2_15524−chr4: 105219622-105219642UACCCCACAAAGCUAUCAAA7219
54790_2_15526−chr4: 105219668-105219688UUCAGCCCUAAAAUCAAGAA7220
54790_2_15544−chr4: 105219818-105219838AUAAUUUAUGAUAUAUUACU7221
54790_2_15545−chr4: 105219819-105219839GAUAAUUUAUGAUAUAUUAC7222
54790_2_15548−chr4: 105219847-105219867CUUAGUUCUCAUAGCCCCUC7223
54790_2_15550−chr4: 105219852-105219872UGCUCCUUAGUUCUCAUAGC7224
54790_2_15551−chr4: 105219853-105219873UUGCUCCUUAGUUCUCAUAG7225
54790_2_15553−chr4: 105219854-105219874AUUGCUCCUUAGUUCUCAUA7226
54790_2_15557−chr4: 105219869-105219889UUUAUUAUCCCGUCGAUUGC7227
54790_2_15561−chr4: 105219881-105219901CCUUUUUGUUUCUUUAUUAU7228
54790_2_15562−chr4: 105219882-105219902CCCUUUUUGUUUCUUUAUUA7229
54790_2_15567−chr4: 105219902-105219922UUCUUUUACAACUCACGAUU7230
54790_2_15568−chr4: 105219903-105219923AUUCUUUUACAACUCACGAU7231
54790_2_15574−chr4: 105219926-105219946UCUUUCAUUUAAUACACCAC7232
54790_2_15575−chr4: 105219931-105219951GUUAUUCUUUCAUUUAAUAC7233
54790_2_15582−chr4: 105219970-105219990AACCUGGACUAUAAGAUUAC7234
54790_2_15585−chr4: 105219989-105220009CUAUUUAUGAGGACAGAAGA7235
54790_2_15593−chr4: 105220052-105220072AACUUGUAUAAGAUACACAG7236
54790_2_15601−chr4: 105220104-105220124GUUAUAAAAAUAAUCUGUCA7237
54790_2_15605−chr4: 105220131-105220151GUGUAGUUAUAUAAUGACAC7238
54790_2_15610−chr4: 105220168-105220188ACUUUAUGUAAUUUCUAGGA7239
54790_2_15611−chr4: 105220169-105220189AACUUUAUGUAAUUUCUAGG7240
54790_2_15614−chr4: 105220172-105220192AAGAACUUUAUGUAAUUUCU7241
54790_2_15620−chr4: 105220209-105220229UAAUGUAUAGGCCAACAAAU7242
54790_2_15621−chr4: 105220210-105220230GUAAUGUAUAGGCCAACAAA7243
54790_2_15627−chr4: 105220221-105220241AGGUUAUCUUGGUAAUGUAU7244
54790_2_15636−chr4: 105220253-105220273UGAAAGUAAAAAUAUAUGCC7245
54790_2_15638−chr4: 105220256-105220276UUAUGAAAGUAAAAAUAUAU7246
54790_2_15642−chr4: 105220294-105220314UGAUAUUAUCAUAUAUACUC7247
54790_2_15643−chr4: 105220295-105220315CUGAUAUUAUCAUAUAUACU7248
54790_2_15645−chr4: 105220296-105220316UCUGAUAUUAUCAUAUAUAC7249
54790_2_15649−chr4: 105220319-105220339AAUUACCGACUUACCCCACU7250
54790_2_15653−chr4: 105220325-105220345UUCUGUAAUUACCGACUUAC7251
54790_2_15654−chr4: 105220326-105220346CUUCUGUAAUUACCGACUUA7252
54790_2_15656−chr4: 105220327-105220347UCUUCUGUAAUUACCGACUU7253
54790_2_15660−chr4: 105220335-105220355GGACCAGUUCUUCUGUAAUU7254
54790_2_15664−chr4: 105220353-105220373CGACAUUUUUAAUACAAUGG7255
54790_2_15667−chr4: 105220377-105220397UUUAACAAGAUUAUUGGUUU7256
54790_2_15677−chr4: 105220421-105220441AACCCUCAAAAUUUUACUUA7257
54790_2_15680−chr4: 105220439-105220459GUGACUGAGUCCGAACUCAA7258
54790_2_15683−chr4: 105220440-105220460UGUGACUGAGUCCGAACUCA7259
54790_2_15686−chr4: 105220450-105220470ACCCUCUUCUUGUGACUGAG7260
54790_2_15696−chr4: 105220469-105220489GGUCACAAAUUCAAACACGA7261
54790_2_15699−chr4: 105220470-105220490CGGUCACAAAUUCAAACACG7262
54790_2_15703−chr4: 105220494-105220514GAUGAAAGUUGAGGUUCCCA7263
54790_2_15706−chr4: 105220498-105220518AGGGGAUGAAAGUUGAGGUU7264
54790_2_15707−chr4: 105220499-105220519GAGGGGAUGAAAGUUGAGGU7265
54790_2_15709−chr4: 105220522-105220542CUCCCCUCCAUAGUCCUCAC7266
54790_2_15711−chr4: 105220529-105220549UCUCCCCCUCCCCUCCAUAG7267
54790_2_15714−chr4: 105220536-105220556AGUGCCAUCUCCCCCUCCCC7268
54790_2_15715−chr4: 105220539-105220559ACGAGUGCCAUCUCCCCCUC7269
54790_2_15717−chr4: 105220540-105220560CACGAGUGCCAUCUCCCCCU7270
54790_2_15719−chr4: 105220541-105220561CCACGAGUGCCAUCUCCCCC7271
54790_2_15723−chr4: 105220544-105220564UGACCACGAGUGCCAUCUCC7272
54790_2_15724−chr4: 105220545-105220565GUGACCACGAGUGCCAUCUC7273
54790_2_15726−chr4: 105220546-105220566CGUGACCACGAGUGCCAUCU7274
54790_2_15728−chr4: 105220547-105220567CCGUGACCACGAGUGCCAUC7275
54790_2_15732−chr4: 105220553-105220573GAGGAUCCGUGACCACGAGU7276
54790_2_15733−chr4: 105220562-105220582GACGGGUUAGAGGAUCCGUG7277
54790_2_15735−chr4: 105220568-105220588AGUCAGGACGGGUUAGAGGA7278
54790_2_15744−chr4: 105220617-105220637GUCAGAACAAGUCCACGAAU7279
54790_2_15746−chr4: 105220626-105220646UUUCAGGAGGUCAGAACAAG7280
54790_2_15748−chr4: 105220668-105220688AGGUUAUCGGUCAGUUACGG7281
54790_2_15750−chr4: 105220693-105220713AGCCUACGGACGGAGUGUCU7282
54790_2_15751−chr4: 105220694-105220714AAGCCUACGGACGGAGUGUC7283
54790_2_15754−chr4: 105220712-105220732UACAGUUCUUUCGGUCAUAA7284
54790_2_15760−chr4: 105220758-105220778ACACGUCACUCUCGGGAACA7285
54790_2_15763−chr4: 105220784-105220804UCCUGUCUAGAGAGGAUAGU7286
54790_2_15764−chr4: 105220785-105220805UUCCUGUCUAGAGAGGAUAG7287
54790_2_15766−chr4: 105220804-105220824GAUACCACUAUCUUCUUUAU7288
54790_2_15771−chr4: 105220821-105220841UCCGUUUCGACUUCAUCGAU7289
54790_2_15773−chr4: 105220841-105220861CUGACACCCCACCUGAGUCG7290
54790_2_15774−chr4: 105220851-105220871UCGUCUUUCUCUGACACCCC7291
54790_2_15776−chr4: 105220854-105220874GGGUCGUCUUUCUCUGACAC7292
54790_2_15777−chr4: 105220855-105220875GGGGUCGUCUUUCUCUGACA7293
54790_2_15778−chr4: 105220856-105220876CGGGGUCGUCUUUCUCUGAC7294
54790_2_15783−chr4: 105220881-105220901CUAAGAAUGACAGGUCCCGU7295
54790_2_15785−chr4: 105220886-105220906AUGCUCUAAGAAUGACAGGU7296
54790_2_15787−chr4: 105220887-105220907CAUGCUCUAAGAAUGACAGG7297
54790_2_15794−chr4: 105220911-105220931UUGCAGAAGUUGUUUAGGCU7298
54790_2_15796−chr4: 105220916-105220936AAAAAUUGCAGAAGUUGUUU7299
54790_2_15810−chr4: 105220994-105221014UCCUUACUGGAACACUGUCU7300
54790_2_15814−chr4: 105221007-105221027UGUGAGCUGGUUGUCCUUAC7301
54790_2_15818−chr4: 105221020-105221040UAGAAUGGAUAAUUGUGAGC7302
54790_2_15823−chr4: 105221035-105221055GUUGACUCCCAUUAUUAGAA7303
54790_2_15841−chr4: 105221162-105221182UGGUUUGAUCACACAUGACU7304
54790_2_15855−chr4: 105221201-105221221UUUGAAUUUGGGCUUAAAGG7305
54790_2_15857−chr4: 105221212-105221232UGGAAUUGUUUUUUGAAUUU7306
54790_2_15859−chr4: 105221213-105221233CUGGAAUUGUUUUUUGAAUU7307
54790_2_15865−chr4: 105221232-105221252UAGGUGAAUAGACAAUAUCC7308
54790_2_15877−chr4: 105221289-105221309UUAACCAACCAGUUUCUUAU7309
54790_2_15886−chr4: 105221360-105221380AGAGAUCUGCAUUUAAGAUC7310
54790_2_15893−chr4: 105221400-105221420GGAAUGCCAUUGAAGAUGAG7311
54790_2_15902−chr4: 105221421-105221441UUUGAGGGAGAAAAAUUCAG7312
54790_2_15909−chr4: 105221436-105221456AUAAUAUAUAGAUUAUUUGA7313
54790_2_15911−chr4: 105221437-105221457AAUAAUAUAUAGAUUAUUUG7314
54790_2_15920−chr4: 105221477-105221497UUAAAAUCUGUUUCUUAAAA7315
54790_2_15930−chr4: 105221526-105221546GUUUUUCAUAAUCCUCAGUA7316
54790_2_15931−chr4: 105221527-105221547GGUUUUUCAUAAUCCUCAGU7317
54790_2_15936−chr4: 105221548-105221568UGUGCAUAGGAGGUUUUGUC7318
54790_2_15937−chr4: 105221558-105221578AUCUAAAUCAUGUGCAUAGG7319
54790_2_15938−chr4: 105221561-105221581CUAAUCUAAAUCAUGUGCAU7320
54790_2_15945−chr4: 105221624-105221644AUUUCUGAAAAGGUGUUAAU7321
54790_2_15948−chr4: 105221634-105221654AAGUUCCUCCAUUUCUGAAA7322
54790_2_15953−chr4: 105221694-105221714UUUUUAUUUUUUUUUCUUUU7323
54790_2_15959−chr4: 105221794-105221814CACCCACGUCGCGUGGUCGU7324
54790_2_15960−chr4: 105221812-105221832UACGAUCUACUGCUCAAUCA7325
54790_2_15961−chr4: 105221813-105221833UUACGAUCUACUGCUCAAUC7326
54790_2_15965−chr4: 105221846-105221866CUGCCCCCUCCCUAUCGUAA7327
54790_2_15967−chr4: 105221847-105221867CCUGCCCCCUCCCUAUCGUA7328
54790_2_15971−chr4: 105221857-105221877ACCCCACCCCCCUGCCCCCU7329
54790_2_15973−chr4: 105221858-105221878CACCCCACCCCCCUGCCCCC7330
54790_2_15976−chr4: 105221861-105221881CAACACCCCACCCCCCUGCC7331
54790_2_15977−chr4: 105221862-105221882ACAACACCCCACCCCCCUGC7332
54790_2_15979−chr4: 105221863-105221883GACAACACCCCACCCCCCUG7333
54790_2_15982−chr4: 105221864-105221884UGACAACACCCCACCCCCCU7334
54790_2_15984−chr4: 105221868-105221888CCCCUGACAACACCCCACCC7335
54790_2_15985−chr4: 105221869-105221889ACCCCUGACAACACCCCACC7336
54790_2_15988−chr4: 105221870-105221890GACCCCUGACAACACCCCAC7337
54790_2_15990−chr4: 105221871-105221891AGACCCCUGACAACACCCCA7338
54790_2_15991−chr4: 105221872-105221892GAGACCCCUGACAACACCCC7339
54790_2_15994−chr4: 105221875-105221895UGUGAGACCCCUGACAACAC7340
54790_2_15995−chr4: 105221876-105221896GUGUGAGACCCCUGACAACA7341
54790_2_15997−chr4: 105221877-105221897AGUGUGAGACCCCUGACAAC7342
54790_2_15999−chr4: 105221887-105221907UUCCCCUUGUAGUGUGAGAC7343
54790_2_16000−chr4: 105221888-105221908CUUCCCCUUGUAGUGUGAGA7344
54790_2_16003−chr4: 105221889-105221909CCUUCCCCUUGUAGUGUGAG7345
54790_2_16005−chr4: 105221904-105221924CUUGUGUACCUGUGUCCUUC7346
54790_2_16007−chr4: 105221905-105221925UCUUGUGUACCUGUGUCCUU7347
54790_2_16010−chr4: 105221906-105221926CUCUUGUGUACCUGUGUCCU7348
54790_2_16014−chr4: 105221910-105221930GUUACUCUUGUGUACCUGUG7349
54790_2_16016−chr4: 105221917-105221937UUAACUUGUUACUCUUGUGU7350
54790_2_16023−chr4: 105221940-105221960CGUAUAAGAGUGAGUAUCCA7351
54790_2_16025−chr4: 105221941-105221961GCGUAUAAGAGUGAGUAUCC7352
54790_2_16028−chr4: 105221944-105221964GUGGCGUAUAAGAGUGAGUA7353
54790_2_16035−chr4: 105222011-105222031ACAUCCCUGUACCUACUUUA7354
54790_2_16040−chr4: 105222021-105222041AGUACAGGAAACAUCCCUGU7355
54790_2_16042−chr4: 105222027-105222047UACUCAAGUACAGGAAACAU7356
54790_2_16044−chr4: 105222028-105222048CUACUCAAGUACAGGAAACA7357
54790_2_16048−chr4: 105222074-105222094UUACACCGUGUAUAUGUGGU7358
54790_2_16051−chr4: 105222090-105222110AUCUGACCUAAUUCUUUUAC7359
54790_2_16053−chr4: 105222105-105222125UUACAGGUUGUUACUAUCUG7360
54790_2_16058−chr4: 105222138-105222158AUAAGUGUUAUCGUUUCUGA7361
54790_2_16063−chr4: 105222164-105222184UACGUGUGCAUACAAAUAAC7362
54790_2_16067−chr4: 105222215-105222235UAAUGACCCAAAUAUGGGUU7363
54790_2_16071−chr4: 105222229-105222249CUGACUCGGUAGGGUAAUGA7364
54790_2_16072−chr4: 105222230-105222250ACUGACUCGGUAGGGUAAUG7365
54790_2_16079−chr4: 105222275-105222295CAGUCACACCGCUAAGGAGU7366
54790_2_16080−chr4: 105222276-105222296UCAGUCACACCGCUAAGGAG7367
54790_2_16085−chr4: 105222288-105222308UUGGUAACACCUUCAGUCAC7368
54790_2_16087−chr4: 105222300-105222320CAUUUGAUCAAGUUGGUAAC7369
54790_2_16093−chr4: 105222326-105222346UUGUGAAAAUGCGACAACCA7370
54790_2_16095−chr4: 105222327-105222347CUUGUGAAAAUGCGACAACC7371
54790_2_16097−chr4: 105222330-105222350AUCCUUGUGAAAAUGCGACA7372
54790_2_16099−chr4: 105222349-105222369ACCUCUCCUACACCUCUUUA7373
54790_2_16103−chr4: 105222358-105222378UUGUUCACGACCUCUCCUAC7374
54790_2_16105−chr4: 105222364-105222384CCUGUGUUGUUCACGACCUC7375
54790_2_16108−chr4: 105222369-105222389UCACUCCUGUGUUGUUCACG7376
54790_2_16113−chr4: 105222385-105222405UACCGCUAGUAAUUUUUCAC7377
54790_2_16116−chr4: 105222404-105222424AGUAGAGUGUGGUCAAUCUU7378
54790_2_16122−chr4: 105222464-105222484CUUUUUUACGAGUGGUAGUG7379
54790_2_16131−chr4: 105222545-105222565UUUGUUAGGGUAGUUUUUCA7380
54790_2_16132−chr4: 105222546-105222566GUUUGUUAGGGUAGUUUUUC7381
54790_2_16143−chr4: 105222618-105222638GUUGGAUGAGUAGACUGUUU7382
54790_2_16144−chr4: 105222619-105222639CGUUGGAUGAGUAGACUGUU7383
54790_2_16147−chr4: 105222654-105222674ACUUGUCCGUUGGGUGUUUU7384
54790_2_16148−chr4: 105222669-105222689CUUGAUGGUAGUCUCACUUG7385
54790_2_16153−chr4: 105222691-105222711UUCUCGAAGACGUGUCGUUU7386
54790_2_16158−chr4: 105222728-105222748UUUUCGGUUUUAACUGUUUA7387
54790_2_16160−chr4: 105222729-105222749GUUUUCGGUUUUAACUGUUU7388
54790_2_16163−chr4: 105222755-105222775CAGAUUUUGUGGUUUUCGUU7389
54790_2_16165−chr4: 105222785-105222805AGUGCUGUAUCCGUGCCCGU7390
54790_2_16167−chr4: 105222790-105222810UGGUAAGUGCUGUAUCCGUG7391
54790_2_16168−chr4: 105222791-105222811GUGGUAAGUGCUGUAUCCGU7392
54790_2_16170−chr4: 105222796-105222816CCGUUGUGGUAAGUGCUGUA7393
54790_2_16171−chr4: 105222817-105222837UUUUGGGAUCUUCUUUUGGA7394
54790_2_16180−chr4: 105222873-105222893UAUGUUUUUAGUUAAGUUCU7395
54790_2_16184−chr4: 105222914-105222934GUAUACACCUUUCGACUUUG7396
54790_2_16188−chr4: 105222928-105222948CUUUUGACCGAUCGGUAUAC7397
54790_2_16192−chr4: 105222942-105222962UAUUUACCACGACCCUUUUG7398
54790_2_16195−chr4: 105222950-105222970GGAUAAAUUAUUUACCACGA7399
54790_2_16197−chr4: 105222951-105222971GGGAUAAAUUAUUUACCACG7400
54790_2_16199−chr4: 105222957-105222977UCCUAAGGGAUAAAUUAUUU7401
54790_2_16200−chr4: 105222977-105222997CUUUUUGUUCUUUACCCCUU7402
54790_2_16202−chr4: 105222982-105223002GGACUCUUUUUGUUCUUUAC7403
54790_2_16204−chr4: 105222983-105223003UGGACUCUUUUUGUUCUUUA7404
54790_2_16207−chr4: 105222984-105223004UUGGACUCUUUUUGUUCUUU7405
54790_2_16214−chr4: 105223038-105223058CUUGUCUCGGGAGUCUUUAU7406
54790_2_16220−chr4: 105223065-105223085UUUUGUCUCUAUAUCUAGUU7407
54790_2_16223−chr4: 105223092-105223112GCUGAGCAUGGUCCACCACG7408
54790_2_16224−chr4: 105223098-105223118AGGACUGCUGAGCAUGGUCC7409
54790_2_16226−chr4: 105223104-105223124UGAAAAAGGACUGCUGAGCA7410
54790_2_16229−chr4: 105223118-105223138UACUUCACAUCUCUUGAAAA7411
54790_2_16251−chr4: 105223210-105223230AAGGUGAAUUAAUAUUUUUA7412
54790_2_16254−chr4: 105223229-105223249GAUUAAGUAUGGAGAAUAUA7413
54790_2_16259−chr4: 105223240-105223260UUUCCUAUAUGGAUUAAGUA7414
54790_2_16261−chr4: 105223251-105223271GGAAUAUAAUGUUUCCUAUA7415
54790_2_16264−chr4: 105223272-105223292AGCAAGCCACAUGUUAGACC7416
54790_2_16296−chr4: 105223424-105223444UAAAGAAAGUGUUUUUUAUA7417
54790_2_16298−chr4: 105223425-105223445GUAAAGAAAGUGUUUUUUAU7418
54790_2_16302−chr4: 105223447-105223467GUUGCCAAGUCUCACUCUUG7419
54790_2_16308−chr4: 105223469-105223489AUUACUAUGUAAUAUUGGUA7420
54790_2_16310−chr4: 105223474-105223494UUAAAAUUACUAUGUAAUAU7421
54790_2_16332−chr4: 105223612-105223632UCAAGAUGUGUGCAAUGCUA7422
54790_2_16341−chr4: 105223664-105223684UGGAUUCUUCCUAUCAACAU7423
54790_2_16343−chr4: 105223665-105223685UUGGAUUCUUCCUAUCAACA7424
54790_2_16347−chr4: 105223684-105223704AUUAUUCUCCAAAACUAUUU7425
54790_2_16349−chr4: 105223708-105223728GGCCACACCUCCUGCAUAGA7426
54790_2_16350−chr4: 105223729-105223749CUGAGUAAAGAUGAUGUAUA7427
54790_2_16361−chr4: 105223780-105223800UAUUAGUAAUUCAGAGUGUU7428
54790_2_16366−chr4: 105223812-105223832UCUCUGUCACUUCCACUGAC7429
54790_2_16370−chr4: 105223849-105223869UGUUUCAGGAUCAAACUUAC7430
54790_2_16372−chr4: 105223850-105223870GUGUUUCAGGAUCAAACUUA7431
54790_2_16375−chr4: 105223863-105223883UGCUAAAGGCACUGUGUUUC7432
54790_2_16378−chr4: 105223877-105223897AUGGGAACUAUAUCUGCUAA7433
54790_2_16381−chr4: 105223895-105223915ACUUCAGACUGCUUGCUUAU7434
54790_2_16383−chr4: 105223896-105223916UACUUCAGACUGCUUGCUUA7435
54790_2_16392−chr4: 105223923-105223943UUAUACAUUCAGAUUACUGA7436
54790_2_16393−chr4: 105223924-105223944UUUAUACAUUCAGAUUACUG7437
54790_2_16411−chr4: 105224037-105224057UGUAUAGUUGCCAUACUAUA7438
54790_2_16424−chr4: 105224083-105224103UAUGUCAGCUUUUUUUCAAG7439
54790_2_16426−chr4: 105224084-105224104UUAUGUCAGCUUUUUUUCAA7440
54790_2_16427−chr4: 105224085-105224105UUUAUGUCAGCUUUUUUUCA7441
54790_2_16445−chr4: 105224151-105224171AAAUAACGAAAACUAGGUGG7442
54790_2_16447−chr4: 105224152-105224172CAAAUAACGAAAACUAGGUG7443
54790_2_16450−chr4: 105224153-105224173CCAAAUAACGAAAACUAGGU7444
54790_2_16452−chr4: 105224154-105224174ACCAAAUAACGAAAACUAGG7445
54790_2_16457−chr4: 105224157-105224177AAAACCAAAUAACGAAAACU7446
54790_2_16467−chr4: 105224174-105224194AAACAAAAACAAAAUAAAAA7447
54790_2_16470−chr4: 105224203-105224223UAUGCUCAAAUUUGUGAAGA7448
54790_2_16471−chr4: 105224204-105224224AUAUGCUCAAAUUUGUGAAG7449
54790_2_16479−chr4: 105224258-105224278CUCUUCGGAUUACUCAAGAA7450
54790_2_16484−chr4: 105224273-105224293CUCCAUACCAUUUGACUCUU7451
54790_2_16490−chr4: 105224308-105224328CAUUUCACCAAUAUGCAUUU7452
54790_2_16493−chr4: 105224341-105224361AUAGCACAUUAGUGUGCAAA7453
54790_2_16500−chr4: 105224398-105224418UAAUCCAUCAUAAUUAUGAC7454
54790_2_16502−chr4: 105224436-105224456GUGAAACAAUUACUGCAUCU7455
54790_2_16510−chr4: 105224467-105224487AUUAUAAAUUCUAGUCGCAU7456
54790_2_16530−chr4: 105224551-105224571UGGUUUCCUAAGACCAAAAC7457
54790_2_16534−chr4: 105224571-105224591UUGACUACUAGCUAACAUUU7458
54790_2_16538−chr4: 105224598-105224618UUUAUCUCAGUUGAAAAUAC7459
54790_2_16546−chr4: 105224640-105224660ACCUUUAUCUUCUAUGUCAG7460
54790_2_16549−chr4: 105224683-105224703UCUCUCUCUCUCUCUCUCUC7461
54790_2_16578−chr4: 105224784-105224804AGAAACAUGCAACAAUUAUA7462
54790_2_16584−chr4: 105224822-105224842CUAAAGGUCAAAUUAUAACC7463
54790_2_16591−chr4: 105224838-105224858AUUUUUUUCAGAAAUUCUAA7464
54790_2_16602−chr4: 105224899-105224919UUGUAAUGCAUGGGCUUCCA7465
54790_2_16605−chr4: 105224908-105224928UAAUGUUCUUUGUAAUGCAU7466
54790_2_16606−chr4: 105224909-105224929CUAAUGUUCUUUGUAAUGCA7467
54790_2_16621−chr4: 105224989-105225009AAUUAAAUUACAAUUUUAAA7468
54790_2_16637−chr4: 105225049-105225069GUAUUUUUUUAAGUCUAAAA7469
54790_2_16639−chr4: 105225071-105225091UGCUAAAGUUAUAAGAACUU7470
54790_2_16653−chr4: 105225134-105225154UCUUCAUAGGUUUACCAAAA7471
54790_2_16654−chr4: 105225147-105225167GCAGCAUGAGAUUUCUUCAU7472
54790_2_16661−chr4: 105225171-105225191UGUGUGGAUUUUUUACUAUA7473
54790_2_16673−chr4: 105225283-105225303CCUUAACCUAGGAAAAUACA7474
54790_2_16677−chr4: 105225294-105225314GAUUAUUGAACCCUUAACCU7475
54790_2_16686−chr4: 105225341-105225361UUUCAAAAAAACUAGUGAGA7476
54790_2_16695−chr4: 105225427-105225447GGAGGAGAACCAGUGACCUA7477
54790_2_16702−chr4: 105225445-105225465ACCUACAACAUUGCUGAGGG7478
54790_2_16704−chr4: 105225448-105225468GCUACCUACAACAUUGCUGA7479
54790_2_16707−chr4: 105225449-105225469AGCUACCUACAACAUUGCUG7480
54790_2_16712−chr4: 105225493-105225513AACACUAAGUCAAAGGUAAA7481
54790_2_16713−chr4: 105225500-105225520AGAGAAAAACACUAAGUCAA7482
54790_2_16726−chr4: 105225584-105225604GCUCUUGUCCCUGUCAAUGU7483
54790_2_16727−chr4: 105225585-105225605AGCUCUUGUCCCUGUCAAUG7484
54790_2_16731−chr4: 105225616-105225636GCCAUGGGAAUACAGGAGAG7485
54790_2_16732−chr4: 105225617-105225637UGCCAUGGGAAUACAGGAGA7486
54790_2_16735−chr4: 105225618-105225638GUGCCAUGGGAAUACAGGAG7487
54790_2_16739−chr4: 105225623-105225643CUGAAGUGCCAUGGGAAUAC7488
54790_2_16741−chr4: 105225631-105225651UGAGACUACUGAAGUGCCAU7489
54790_2_16743−chr4: 105225632-105225652AUGAGACUACUGAAGUGCCA7490
54790_2_16750−chr4: 105225657-105225677CCUGAACUGUGGUUAUGUUG7491
54790_2_16752−chr4: 105225668-105225688UCCUCUACUGCCCUGAACUG7492
54790_2_16755−chr4: 105225713-105225733UCAGUGCAGUUGCCAUGGCA7493
54790_2_16758−chr4: 105225718-105225738CUCACUCAGUGCAGUUGCCA7494
54790_2_16773−chr4: 105225797-105225817GAUAAUGUCACUCAGAGAAU7495
54790_2_16786−chr4: 105225840-105225860AUUUUUCUCUAGAAUAUUUG7496
54790_2_16794−chr4: 105225873-105225893CCAGAUUAUCUUUGCAAUGC7497
54790_2_16809−chr4: 105225944-105225964AAACGUAAACUUUUAGGACA7498
54790_2_16811−chr4: 105225950-105225970AAAAGAAAACGUAAACUUUU7499
54790_2_16821−chr4: 105225982-105226002AUCAUUUCUUUAUGUGGUUU7500
54790_2_16822−chr4: 105225983-105226003AAUCAUUUCUUUAUGUGGUU7501
54790_2_16827−chr4: 105225988-105226008CAACAAAUCAUUUCUUUAUG7502
54790_2_16835−chr4: 105226030-105226050GUAAUUAUUAAGAUGAUUAA7503
54790_2_16836−chr4: 105226031-105226051UGUAAUUAUUAAGAUGAUUA7504
54790_2_16841−chr4: 105226056-105226076UAUUUUGGCUACGUAUCUGU7505
54790_2_16845−chr4: 105226071-105226091GGAUUAAAAAACAAGUAUUU7506
54790_2_16856−chr4: 105226092-105226112AAGCUUUUUUUUUAAGGUUU7507
54790_2_16858−chr4: 105226098-105226118CAAUUUAAGCUUUUUUUUUA7508
54790_2_16869−chr4: 105226155-105226175AAAGACAAGUGCAUAAUUAA7509
54790_2_16872−chr4: 105226211-105226231CCCUGAUCCGGAUUCGUGAG7510
54790_2_16873−chr4: 105226225-105226245GUCUCCGAGGGUGUCCCUGA7511
54790_2_16874−chr4: 105226231-105226251GGUUUUGUCUCCGAGGGUGU7512
54790_2_16876−chr4: 105226232-105226252UGGUUUUGUCUCCGAGGGUG7513
54790_2_16878−chr4: 105226242-105226262UACCACUUCGUGGUUUUGUC7514
54790_2_16881−chr4: 105226261-105226281UUUUGACUCCUUAGACGGGU7515
54790_2_16887−chr4: 105226274-105226294AAAAUUUCUACACUUUUGAC7516
54790_2_16895−chr4: 105226316-105226336AACAUUUCAGAGUAGCAGCU7517
54790_2_16898−chr4: 105226354-105226374UAAGUAAUAAUAUGUAACAA7518
54790_2_16900−chr4: 105226390-105226410GUCACGGCUAAGAAAUUCUA7519
54790_2_16902−chr4: 105226406-105226426UUGUUGGUUUGGUAUAGUCA7520
54790_2_16909−chr4: 105226433-105226453AUAAAGUUGUCCUCUAAAUC7521
54790_2_16912−chr4: 105226444-105226464UGACCCCUAAUAUAAAGUUG7522
54790_2_16915−chr4: 105226460-105226480CCGGGGGUGGAGGUUGUGAC7523
54790_2_16917−chr4: 105226461-105226481UCCGGGGGUGGAGGUUGUGA7524
54790_2_16919−chr4: 105226462-105226482GUCCGGGGGUGGAGGUUGUG7525
54790_2_16922−chr4: 105226481-105226501AUUAGGUUUGUGAAGGGUGG7526
54790_2_16923−chr4: 105226515-105226535UCCUGUCGUGGUACGGUACU7527
54790_2_16925−chr4: 105226516-105226536CUCCUGUCGUGGUACGGUAC7528
54790_2_16929−chr4: 105226535-105226555GAACUCUUGAGUGAUAGUCC7529
54790_2_16932−chr4: 105226538-105226558AGAGAACUCUUGAGUGAUAG7530
54790_2_16938−chr4: 105226585-105226605CUCCCUUCCUCUGUCCCUCC7531
54790_2_16939−chr4: 105226586-105226606CCUCCCUUCCUCUGUCCCUC7532
54790_2_16941−chr4: 105226587-105226607CCCUCCCUUCCUCUGUCCCU7533
54790_2_16944−chr4: 105226588-105226608UCCCUCCCUUCCUCUGUCCC7534
54790_2_16946−chr4: 105226591-105226611CUCUCCCUCCCUUCCUCUGU7535
54790_2_16949−chr4: 105226592-105226612UCUCUCCCUCCCUUCCUCUG7536
54790_2_16951−chr4: 105226599-105226619CCCUUCCUCUCUCCCUCCCU7537
54790_2_16955−chr4: 105226603-105226623CCCUCCCUUCCUCUCUCCCU7538
54790_2_16956−chr4: 105226604-105226624UCCCUCCCUUCCUCUCUCCC7539
54790_2_16960−chr4: 105226607-105226627GUCUCCCUCCCUUCCUCUCU7540
54790_2_16962−chr4: 105226608-105226628UGUCUCCCUCCCUUCCUCUC7541
54790_2_16966−chr4: 105226615-105226635CCCUUCCUGUCUCCCUCCCU7542
54790_2_16970−chr4: 105226619-105226639CCCUCCCUUCCUGUCUCCCU7543
54790_2_16971−chr4: 105226620-105226640UCCCUCCCUUCCUGUCUCCC7544
54790_2_16974−chr4: 105226623-105226643UUCUCCCUCCCUUCCUGUCU7545
54790_2_16977−chr4: 105226624-105226644CUUCUCCCUCCCUUCCUGUC7546
54790_2_16980−chr4: 105226631-105226651CUCCCUCCUUCUCCCUCCCU7547
54790_2_16982−chr4: 105226635-105226655CCUUCUCCCUCCUUCUCCCU7548
54790_2_16985−chr4: 105226636-105226656UCCUUCUCCCUCCUUCUCCC7549
54790_2_16987−chr4: 105226639-105226659CUCUCCUUCUCCCUCCUUCU7550
54790_2_16989−chr4: 105226640-105226660UCUCUCCUUCUCCCUCCUUC7551
54790_2_16994−chr4: 105226646-105226666UUUUUCUCUCUCCUUCUCCC7552
54790_2_16996−chr4: 105226649-105226669CUCUUUUUCUCUCUCCUUCU7553
54790_2_16998−chr4: 105226650-105226670CCUCUUUUUCUCUCUCCUUC7554
54790_2_17003−chr4: 105226656-105226676CCUCACCCUCUUUUUCUCUC7555
54790_2_17010−chr4: 105226671-105226691CGUAGAUUGUACCGACCUCA7556
54790_2_17012−chr4: 105226672-105226692CCGUAGAUUGUACCGACCUC7557
54790_2_17015−chr4: 105226677-105226697CUCGUCCGUAGAUUGUACCG7558
54790_2_17017−chr4: 105226681-105226701UCCCCUCGUCCGUAGAUUGU7559
54790_2_17018−chr4: 105226693-105226713CGUCUUUCGUUUUCCCCUCG7560
54790_2_17021−chr4: 105226699-105226719UAGUACCGUCUUUCGUUUUC7561
54790_2_17023−chr4: 105226700-105226720UUAGUACCGUCUUUCGUUUU7562
54790_2_17024−chr4: 105226701-105226721AUUAGUACCGUCUUUCGUUU7563
54790_2_17029−chr4: 105226715-105226735GGAAUGUUUUGAAUAUUAGU7564
54790_2_17032−chr4: 105226738-105226758UGACCGUAGACGAAACCCAC7565
54790_2_17034−chr4: 105226743-105226763UUUCGUGACCGUAGACGAAA7566
54790_2_17035−chr4: 105226744-105226764GUUUCGUGACCGUAGACGAA7567
54790_2_17037−chr4: 105226756-105226776GACAUAUCCUCCGUUUCGUG7568
54790_2_17039−chr4: 105226767-105226787CCAAGACGUCCGACAUAUCC7569
54790_2_17042−chr4: 105226770-105226790GUACCAAGACGUCCGACAUA7570
54790_2_17046−chr4: 105226779-105226799AUUAACCGAGUACCAAGACG7571
54790_2_17047−chr4: 105226788-105226808UUUAUCCAAAUUAACCGAGU7572
54790_2_17050−chr4: 105226795-105226815AUAUUCUUUUAUCCAAAUUA7573
54790_2_17051−chr4: 105226804-105226824ACCCAUUAAAUAUUCUUUUA7574
54790_2_17054−chr4: 105226823-105226843GAUAUUUCUUUAUCGACAGA7575
54790_2_17055−chr4: 105226824-105226844CGAUAUUUCUUUAUCGACAG7576
54790_2_17070−chr4: 105226860-105226880AACCUUUUGAAAGGAUACAA7577
54790_2_17071−chr4: 105226869-105226889UAGCAUUUUAACCUUUUGAA7578
54790_2_17076−chr4: 105226902-105226922GGACAAAGAGAUCUUGCUUC7579
54790_2_17087−chr4: 105226923-105226943CAUCUUUAUUUCCAGAAUUC7580
54790_2_17091−chr4: 105226946-105226966AAAUACAUGCCAUAUUAUUU7581
54790_2_17113−chr4: 105227057-105227077GUGUUACACGAGAACUCUUG7582
54790_2_17122−chr4: 105227123-105227143AUGCUCUUAUGGGUUAUAGC7583
54790_2_17124−chr4: 105227133-105227153UCCUCAGGAGAUGCUCUUAU7584
54790_2_17125−chr4: 105227134-105227154UUCCUCAGGAGAUGCUCUUA7585
54790_2_17132−chr4: 105227148-105227168CAGUUUUUAACAUAUUCCUC7586
54790_2_17149−chr4: 105227231-105227251AGUGACUAAUUGUUUACCCA7587
54790_2_17151−chr4: 105227232-105227252GAGUGACUAAUUGUUUACCC7588
54790_2_17156−chr4: 105227254-105227274GAAGAACCUUUGGGAAAACC7589
54790_2_17158−chr4: 105227263-105227283ACAGAGACAGAAGAACCUUU7590
54790_2_17160−chr4: 105227264-105227284AACAGAGACAGAAGAACCUU7591
54790_2_17181−chr4: 105227307-105227327CUUUUUUGGGGUUGUUAAAC7592
54790_2_17183−chr4: 105227319-105227339CAAAAUUAAGGCCUUUUUUG7593
54790_2_17184−chr4: 105227320-105227340UCAAAAUUAAGGCCUUUUUU7594
54790_2_17185−chr4: 105227321-105227341AUCAAAAUUAAGGCCUUUUU7595
54790_2_17188−chr4: 105227331-105227351AUGCUGGCCAAUCAAAAUUA7596
54790_2_17191−chr4: 105227347-105227367UGUCUUUCCUAAGAGGAUGC7597
54790_2_17192−chr4: 105227354-105227374AUGGCAAUGUCUUUCCUAAG7598
54790_2_17197−chr4: 105227373-105227393GAAGCAACUUUACAAGAGGA7599
54790_2_17199−chr4: 105227377-105227397AUGAGAAGCAACUUUACAAG7600
54790_2_17211−chr4: 105227419-105227439UAUAAAAAUCAUUCCCUAGA7601
54790_2_17221−chr4: 105227498-105227518UUCAAACACCUUGCUAUUGA7602
54790_2_17226−chr4: 105227561-105227581CAGAGAACACAAAAUUAAUA7603
54790_2_17275−chr4: 105227738-105227758AUAAAUAUAAAUUUUUGCUA7604
54790_2_17326−chr4: 105227968-105227988UUCAUGCUGUAGUUUUUAUG7605
54790_2_17327−chr4: 105227969-105227989UUUCAUGCUGUAGUUUUUAU7606
54790_2_17328−chr4: 105227970-105227990CUUUCAUGCUGUAGUUUUUA7607
54790_2_17344−chr4: 105228038-105228058AUUUUGCUUAAUAAAAGAGA7608
54790_2_17360−chr4: 105228140-105228160CACUUUUUAUAUACAUACCC7609
54790_2_17375−chr4: 105228207-105228227UAAUAAACUGCCAUUUUAGA7610
54790_2_17389−chr4: 105228240-105228260UGGUCUUUAAAUCUUAUUUC7611
54790_2_17395−chr4: 105228260-105228280GAAUGAGGAAAAUUUGUUAU7612
54790_2_17398−chr4: 105228275-105228295GAAAGUUAUAUGUUAGAAUG7613
54790_2_17408−chr4: 105228297-105228317AACUUUUUCACAAGAAGGGC7614
54790_2_17411−chr4: 105228301-105228321GGUUAACUUUUUCACAAGAA7615
54790_2_17413−chr4: 105228302-105228322UGGUUAACUUUUUCACAAGA7616
54790_2_17419−chr4: 105228322-105228342CAUUUGUGUGAAAAGUUUAA7617
54790_2_17438−chr4: 105228403-105228423AUAUGGAGUUUUAAACACAA7618
54790_2_17440−chr4: 105228420-105228440AAAAGAAAUGUAUUUCAAUA7619
54790_2_17443−chr4: 105228450-105228470UAAUAGCUACUAAGAAAUGA7620
54790_2_17455−chr4: 105228491-105228511GACAUUCUUUAAAGUGUCAA7621
54790_2_17456−chr4: 105228492-105228512GGACAUUCUUUAAAGUGUCA7622
54790_2_17460−chr4: 105228513-105228533UAAUCCAUUCCACAUAAUUU7623
54790_2_17477−chr4: 105228576-105228596ACAUGUUUUUCUACUUUCUA7624
54790_2_17482−chr4: 105228612-105228632AUAAAUUAUAUAAAAUUUGU7625
54790_2_17488−chr4: 105228667-105228687UCAUAUACAGAGCAAUCAAA7626
54790_2_17496−chr4: 105228708-105228728AAAAAAAGGCACUUUUCUUU7627
54790_2_17498−chr4: 105228722-105228742GUCCAGAUACUACCAAAAAA7628
54790_2_17506−chr4: 105228795-105228815CUAUCACUUUUCAAAAAUUA7629
54790_2_17509−chr4: 105228821-105228841UGAGAGGCUUCUCCAAAAUC7630
54790_2_17516−chr4: 105228837-105228857UUUGUAGUCUUUGAUAUGAG7631
54790_2_17525−chr4: 105228881-105228901ACACCUAAUAAAGAAACUUU7632
54790_2_17532−chr4: 105228920-105228940AGAAAAUUUGGGUGAGACAA7633
54790_2_17537−chr4: 105228931-105228951UAACUUGUAGUAGAAAAUUU7634
54790_2_17538−chr4: 105228932-105228952AUAACUUGUAGUAGAAAAUU7635
54790_2_17545−chr4: 105228970-105228990UCUUUUACAUUUUAAGGUAC7636
54790_2_17566−chr4: 105229049-105229069ACUUGAUAAAAUUUACAUAA7637
54790_2_17567−chr4: 105229050-105229070AACUUGAUAAAAUUUACAUA7638
54790_2_17581−chr4: 105229131-105229151UAGAUACUUUUGUAAAUCAA7639
54790_2_17585−chr4: 105229155-105229175CAGAUCAGGUUUAACUCUAC7640
54790_2_17595−chr4: 105229238-105229258UCCUUCCAUACAUUAACUCU7641
54790_2_17606−chr4: 105229304-105229324UUAUUUGUUAUAACUCAUAU7642
54790_2_17610−chr4: 105229354-105229374GCGCGGUGACGUGAGGUCGG7643
54790_2_17616−chr4: 105229394-105229414GUAAACUUGGGUCCUCCGCC7644
54790_2_17618−chr4: 105229397-105229417UUAGUAAACUUGGGUCCUCC7645
54790_2_17620−chr4: 105229400-105229420CUCUUAGUAAACUUGGGUCC7646
54790_2_17621−chr4: 105229403-105229423GUCCUCUUAGUAAACUUGGG7647
54790_2_17628−chr4: 105229422-105229442CAAUGAACCCUCCGACUCCG7648
54790_2_17631−chr4: 105229426-105229446GGGUCAAUGAACCCUCCGAC7649
54790_2_17633−chr4: 105229432-105229452ACAUCAGGGUCAAUGAACCC7650
54790_2_17635−chr4: 105229435-105229455CGGACAUCAGGGUCAAUGAA7651
54790_2_17636−chr4: 105229436-105229456ACGGACAUCAGGGUCAAUGA7652
54790_2_17639−chr4: 105229463-105229483GUUUUUCAUCGACCCGUACC7653
54790_2_17640−chr4: 105229466-105229486UAUGUUUUUCAUCGACCCGU7654
54790_2_17641−chr4: 105229471-105229491AUUUUUAUGUUUUUCAUCGA7655
54790_2_17642−chr4: 105229472-105229492GAUUUUUAUGUUUUUCAUCG7656
54790_2_17645−chr4: 105229511-105229531GCUCUGGUAGAACCGGUUGC7657
54790_2_17646−chr4: 105229520-105229540AGUUCUCUAGCUCUGGUAGA7658
54790_2_17649−chr4: 105229543-105229563CGACUCCGUCCGUCUAGUGC7659
54790_2_17653−chr4: 105229555-105229575CGUGAAACCCUCCGACUCCG7660
54790_2_17654−chr4: 105229559-105229579GGGUCGUGAAACCCUCCGAC7661
54790_2_17656−chr4: 105229565-105229585ACAUCAGGGUCGUGAAACCC7662
54790_2_17657−chr4: 105229568-105229588CGGACAUCAGGGUCGUGAAA7663
54790_2_17659−chr4: 105229569-105229589GCGGACAUCAGGGUCGUGAA7664
54790_2_17662−chr4: 105229596-105229616UUUAUUUACCGGUCCGUGCC7665
54790_2_17663−chr4: 105229599-105229619UAUUUUAUUUACCGGUCCGU7666
54790_2_17666−chr4: 105229604-105229624UUAUUUAUUUUAUUUACCGG7667
54790_2_17667−chr4: 105229609-105229629AUGAAUUAUUUAUUUUAUUU7668
54790_2_17687−chr4: 105229687-105229707ACCUCUUUUCGUGACCCUCC7669
54790_2_17688−chr4: 105229688-105229708GACCUCUUUUCGUGACCCUC7670
54790_2_17690−chr4: 105229689-105229709CGACCUCUUUUCGUGACCCU7671
54790_2_17693−chr4: 105229690-105229710UCGACCUCUUUUCGUGACCC7672
54790_2_17695−chr4: 105229693-105229713CCGUCGACCUCUUUUCGUGA7673
54790_2_17697−chr4: 105229694-105229714CCCGUCGACCUCUUUUCGUG7674
54790_2_17702−chr4: 105229707-105229727UCCUUUUCCUUACCCCGUCG7675
54790_2_17706−chr4: 105229714-105229734ACGGAGGUCCUUUUCCUUAC7676
54790_2_17707−chr4: 105229715-105229735AACGGAGGUCCUUUUCCUUA7677
54790_2_17708−chr4: 105229716-105229736AAACGGAGGUCCUUUUCCUU7678
54790_2_17712−chr4: 105229721-105229741UUAUUAAACGGAGGUCCUUU7679
54790_2_17714−chr4: 105229727-105229747CCGGUAUUAUUAAACGGAGG7680
54790_2_17717−chr4: 105229748-105229768GACCUCUUAUAUAUUACUUG7681
54790_2_17722−chr4: 105229767-105229787AAAUAAAAAAAAAUCUAGAG7682
54790_2_17729−chr4: 105229838-105229858GGUCAUUAAUUUACCUUAUU7683
54790_2_17732−chr4: 105229846-105229866UCAUAGAGGGUCAUUAAUUU7684
54790_2_17739−chr4: 105229870-105229890UCAUAGAGAUAUAAAAGUCU7685
54790_2_17747−chr4: 105229932-105229952CCCAAUACAAUUUAUUAAAU7686
54790_2_17749−chr4: 105229952-105229972CUUUGUUGGAUGUAGUUAUU7687
54790_2_17750−chr4: 105229953-105229973UCUUUGUUGGAUGUAGUUAU7688
54790_2_17756−chr4: 105229978-105229998GUUAGAAAACGUCAUUAUUU7689
54790_2_17758−chr4: 105230003-105230023UAUAUAUGUAAUUUACUACA7690
54790_2_17762−chr4: 105230084-105230104CACUACGACGUGAGGUCGGA7691
54790_2_17763−chr4: 105230085-105230105ACACUACGACGUGAGGUCGG7692
54790_2_17766−chr4: 105230114-105230134UCCUCCACCUGUGACGUCAC7693
54790_2_17768−chr4: 105230128-105230148UUAGUGGACUUGGGUCCUCC7694
54790_2_17770−chr4: 105230131-105230151UUCUUAGUGGACUUGGGUCC7695
54790_2_17771−chr4: 105230134-105230154UUCUUCUUAGUGGACUUGGG7696
54790_2_17780−chr4: 105230157-105230177GGGUCAAUGAACCCUCCGAC7697
54790_2_17784−chr4: 105230163-105230183ACAUUAGGGUCAAUGAACCC7698
54790_2_17785−chr4: 105230166-105230186UGGACAUUAGGGUCAAUGAA7699
54790_2_17788−chr4: 105230167-105230187GUGGACAUUAGGGUCAAUGA7700
54790_2_17791−chr4: 105230190-105230210UUAAUCGUCCCGUACCACCA7701
54790_2_17792−chr4: 105230194-105230214GUUUUUAAUCGUCCCGUACC7702
54790_2_17793−chr4: 105230197-105230217UAUGUUUUUAAUCGUCCCGU7703
54790_2_17794−chr4: 105230202-105230222UUUUCUAUGUUUUUAAUCGU7704
54790_2_17795−chr4: 105230203-105230223UUUUUCUAUGUUUUUAAUCG7705
54790_2_17799−chr4: 105230244-105230264GAUCUGGUUGGACCGGUUGU7706
54790_2_17800−chr4: 105230253-105230273GGUCCUCAAGAUCUGGUUGG7707
54790_2_17801−chr4: 105230271-105230291GGUCACCUAGUGGACUCCGG7708
54790_2_17804−chr4: 105230276-105230296AUUCCGGUCACCUAGUGGAC7709
54790_2_17808−chr4: 105230287-105230307GAAACCCUUCGAUUCCGGUC7710
54790_2_17810−chr4: 105230294-105230314GGGUCGUGAAACCCUUCGAU7711
54790_2_17811−chr4: 105230303-105230323CGGAUAUUAGGGUCGUGAAA7712
54790_2_17813−chr4: 105230304-105230324GCGGAUAUUAGGGUCGUGAA7713
54790_2_17818−chr4: 105230334-105230354AAAUAGACUGUCCGACCCAC7714
54790_2_17822−chr4: 105230339-105230359UUCUUAAAUAGACUGUCCGA7715
54790_2_17823−chr4: 105230340-105230360AUUCUUAAAUAGACUGUCCG7716
54790_2_17825−chr4: 105230344-105230364GAAAAUUCUUAAAUAGACUG7717
54790_2_17835−chr4: 105230404-105230424AUAGUACAUCCUACUGUUAA7718
54790_2_17836−chr4: 105230416-105230436UUGACGGUGUUUAUAGUACA7719
54790_2_17843−chr4: 105230453-105230473UUUUGUCUAUGAGAGAGUAC7720
54790_2_17847−chr4: 105230476-105230496UGAUACAAACCGUUCGUACA7721
54790_2_17849−chr4: 105230477-105230497AUGAUACAAACCGUUCGUAC7722
54790_2_17852−chr4: 105230488-105230508CGAACUAUGAUAUGAUACAA7723
54790_2_17863−chr4: 105230551-105230571ACGUUUAAUUUUGACGUUGU7724
54790_2_17872−chr4: 105230620-105230640GUAUCUUUUACUUUACACUU7725
54790_2_17876−chr4: 105230649-105230669AUUUUUUACCUGUUCCCUGU7726
54790_2_17878−chr4: 105230655-105230675UGUAUGAUUUUUUACCUGUU7727
54790_2_17880−chr4: 105230656-105230676GUGUAUGAUUUUUUACCUGU7728
54790_2_17882−chr4: 105230662-105230682UUAUUGGUGUAUGAUUUUUU7729
54790_2_17890−chr4: 105230702-105230722UAAAACAAAAGAAUUGUAUA7730
54790_2_17899−chr4: 105230784-105230804AUCUAGAAGUCAUAAAAGAU7731
54790_2_17900−chr4: 105230785-105230805AAUCUAGAAGUCAUAAAAGA7732
54790_2_17913−chr4: 105230832-105230852ACUUAAAAAAAUCUAAUGAC7733
54790_2_17921−chr4: 105230894-105230914ACUUAAAUUAUAAACUUAUG7734
54790_2_17931−chr4: 105230950-105230970AGGACUUUUUUACUAUUUCA7735
54790_2_17933−chr4: 105230951-105230971GAGGACUUUUUUACUAUUUC7736
54790_2_17938−chr4: 105230978-105230998AUGAACUAUAAUCUUGUUGA7737
54790_2_17939−chr4: 105230979-105230999UAUGAACUAUAAUCUUGUUG7738
54790_2_17945−chr4: 105231013-105231033UAUACGAUGUUCUAUUCCUA7739
54790_2_17947−chr4: 105231014-105231034UUAUACGAUGUUCUAUUCCU7740
54790_2_17949−chr4: 105231018-105231038GUCUUUAUACGAUGUUCUAU7741
54790_2_17956−chr4: 105231076-105231096AUAUUAUAAUUAUACUAGUU7742
54790_2_17968−chr4: 105231170-105231190AAGACUUUUUCUUAACAUAC7743
54790_2_17969−chr4: 105231171-105231191UAAGACUUUUUCUUAACAUA7744
54790_2_17971−chr4: 105231172-105231192AUAAGACUUUUUCUUAACAU7745
54790_2_17977−chr4: 105231197-105231217UUAUUUGUUUAACCCAUCGG7746
54790_2_17982−chr4: 105231205-105231225AAACCUUUUUAUUUGUUUAA7747
54790_2_17983−chr4: 105231206-105231226UAAACCUUUUUAUUUGUUUA7748
54790_2_17987−chr4: 105231223-105231243UCAACUGAGGUUUCAAGUAA7749
54790_2_17994−chr4: 105231247-105231267GUCUUAUAAAACUCCUUAAU7750
54790_2_17997−chr4: 105231255-105231275UCAUGAACGUCUUAUAAAAC7751
54790_2_18009−chr4: 105231339-105231359AUUCAUGUUUUUGUUUUGUU7752
54790_2_18012−chr4: 105231340-105231360UAUUCAUGUUUUUGUUUUGU7753
54790_2_18024−chr4: 105231402-105231422UCCUUAUUCAAAAAUUUUAC7754
54790_2_18028−chr4: 105231422-105231442UAUCUUCUUUAAUUAUGUGA7755
54790_2_18037−chr4: 105231465-105231485GUUGGUCAGUCUUCAAAAUG7756
54790_2_18056−chr4: 105231554-105231574GAUCUCUUAGUUCAUUUUUU7757
54790_2_18062−chr4: 105231582-105231602GUCUAUUUUUCUAAUAUAUG7758
54790_2_18083−chr4: 105231705-105231725AGAAAGACUAUUUUCUUUUU7759
54790_2_18084−chr4: 105231706-105231726AAGAAAGACUAUUUUCUUUU7760
54790_2_18103−chr4: 105231790-105231810AAAAAUUAAUCCAUUGUAUA7761
54790_2_18104−chr4: 105231819-105231839AUAGAGAAAGCCAGAAGAAA7762
54790_2_18128−chr4: 105231945-105231965CAGACAUGUGGUUUGGGGGU7763
54790_2_18132−chr4: 105231978-105231998UUCAUGAUGCGAAUAAUGGA7764
54790_2_18133−chr4: 105231979-105231999AUUCAUGAUGCGAAUAAUGG7765
54790_2_18137−chr4: 105232019-105232039AACUCCUACCCUCUUCCCUC7766
54790_2_18141−chr4: 105232024-105232044UAUGAAACUCCUACCCUCUU7767
54790_2_18143−chr4: 105232025-105232045CUAUGAAACUCCUACCCUCU7768
54790_2_18148−chr4: 105232031-105232051UCGUCCCUAUGAAACUCCUA7769
54790_2_18149−chr4: 105232032-105232052GUCGUCCCUAUGAAACUCCU7770
54790_2_18152−chr4: 105232036-105232056GUCUGUCGUCCCUAUGAAAC7771
54790_2_18155−chr4: 105232047-105232067UCCCCCUUGUUGUCUGUCGU7772
54790_2_18157−chr4: 105232048-105232068CUCCCCCUUGUUGUCUGUCG7773
54790_2_18159−chr4: 105232064-105232084UUGUGUACCUGUGUUUCUCC7774
54790_2_18161−chr4: 105232065-105232085CUUGUGUACCUGUGUUUCUC7775
54790_2_18163−chr4: 105232066-105232086UCUUGUGUACCUGUGUUUCU7776
54790_2_18165−chr4: 105232067-105232087UUCUUGUGUACCUGUGUUUC7777
54790_2_18169−chr4: 105232078-105232098UCGAUUUGUCGUUCUUGUGU7778
54790_2_18175−chr4: 105232102-105232122UAUGGUGUACAAGAGAAUUC7779
54790_2_18179−chr4: 105232134-105232154AUAGGAUUUGUUUGAUUGUU7780
54790_2_18181−chr4: 105232161-105232181UCGUUGUACCUACCUCGACC7781
54790_2_18184−chr4: 105232164-105232184ACGUCGUUGUACCUACCUCG7782
54790_2_18187−chr4: 105232170-105232190CAAGACACGUCGUUGUACCU7783
54790_2_18189−chr4: 105232174-105232194AGCACAAGACACGUCGUUGU7784
54790_2_18194−chr4: 105232227-105232247UUUCACAAUGUAUAUGUGGU7785
54790_2_18197−chr4: 105232256-105232276UUACAGGCAUUCAUCAUCUG7786
54790_2_18200−chr4: 105232289-105232309AUAAUUACUAUCGCUUCUGU7787
54790_2_18207−chr4: 105232342-105232362AUAUUUAGUAAGAUGGUAUU7788
54790_2_18211−chr4: 105232366-105232386AUAAGCCGUAUAAUGGGUUU7789
54790_2_18212−chr4: 105232367-105232387AAUAAGCCGUAUAAUGGGUU7790
54790_2_18215−chr4: 105232382-105232402CUGGCUCGUUAGGGUAAUAA7791
54790_2_18222−chr4: 105232422-105232442UUCGUCACGCCAUUAAAGUC7792
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54790_3_1142−chr4: 105238774-105238794UUGUAAGUAUUAAGUACCCU8037
54790_3_1145−chr4: 105238775-105238795CUUGUAAGUAUUAAGUACCC8038
54790_3_1148−chr4: 105238778-105238798AUUCUUGUAAGUAUUAAGUA8039
54790_3_1151−chr4: 105238779-105238799AAUUCUUGUAAGUAUUAAGU8040
54790_3_1161−chr4: 105238821-105238841UGUAACUUUCGGAAGACCUU8041
54790_3_1162−chr4: 105238826-105238846UUUCAUGUAACUUUCGGAAG8042
54790_3_1167−chr4: 105238850-105238870CUAUCAGAAGACUACCUAGG8043
54790_3_1168−chr4: 105238851-105238871UCUAUCAGAAGACUACCUAG8044
54790_3_1170−chr4: 105238857-105238877GACGGUUCUAUCAGAAGACU8045
54790_3_1186−chr4: 105238934-105238954UAAGACGUCGGAUACCUAAU8046
54790_3_1189−chr4: 105238941-105238961UUGUAACUAAGACGUCGGAU8047
54790_3_1197−chr4: 105239004-105239024AUCAGUGGGUUCUCGAGGCU8048
54790_3_1203−chr4: 105239031-105239051AAAGUUUUAUAAUGACGAGU8049
54790_3_1217−chr4: 105239163-105239183UCAUUACCUUGUUGUUUCAG8050
54790_3_1221−chr4: 105239178-105239198UGGGACGAACACAUCUCAUU8051
54790_3_1231−chr4: 105239224-105239244AAUGGUAAGACUUUUAAGGU8052
54790_3_1241−chr4: 105239287-105239307GUCCGACUGAGAGAACAAUG8053
54790_3_1244−chr4: 105239306-105239326UUACGGAACGAAGUUUCCUG8054
54790_3_1245−chr4: 105239311-105239331UUCAGUUACGGAACGAAGUU8055
54790_3_1252−chr4: 105239359-105239379UUGUCGGAUGAUAACUUUGU8056
54790_3_1254−chr4: 105239390-105239410CGAUUCUAGUGACUACUUCC8057
54790_3_1255−chr4: 105239393-105239413GAUCGAUUCUAGUGACUACU8058
54790_3_1262−chr4: 105239460-105239480AUUGUAUUUUCCUGUUCCAC8059
54790_3_1264−chr4: 105239465-105239485GAGAUAUUGUAUUUUCCUGU8060
54790_3_1265−chr4: 105239471-105239491UCGACAGAGAUAUUGUAUUU8061
54790_3_1275−chr4: 105239515-105239535UCAACCUUCGAUCGUCUUCA8062
54790_3_1279−chr4: 105239532-105239552CCUUCGACGUCUUCUCUUCA8063
54790_3_1289−chr4: 105239553-105239573AGUCAAGAUACUUCUCUUAC8064
54790_3_1298−chr4: 105239588-105239608GGUUUCGAAUUAGGUCUCGU8065
54790_3_1305−chr4: 105239645-105239665ACCUCUCGCGAAAUCACCAG8066
54790_3_1308−chr4: 105239650-105239670ACUAUACCUCUCGCGAAAUC8067
54790_3_1312−chr4: 105239665-105239685UUUGCCGGAAUAACGACUAU8068
54790_3_1314−chr4: 105239682-105239702ACUUUCCAUUCUUUCGUUUU8069
54790_3_1317−chr4: 105239698-105239718AUGAGGUCACUUGUGUACUU8070
54790_3_1322−chr4: 105239725-105239745ACAUUUCCUUUUUAAGAACU8071
54790_3_1329−chr4: 105239740-105239760AUCGGUUCAACACUUACAUU8072
54790_3_1333−chr4: 105239777-105239797CGGUUCUGUCCGACUUUCGA8073
54790_3_1335−chr4: 105239789-105239809CCGUACAGUUUUCGGUUCUG8074
54790_3_1336−chr4: 105239810-105239830AUACUGCUCGAUUCACUCCU8075
54790_3_1337−chr4: 105239814-105239834AUCUAUACUGCUCGAUUCAC8076
54790_3_1348−chr4: 105239871-105239891GGAGAUUCACAAGUUCACUU8077
54790_3_1353−chr4: 105239894-105239914CGGUUAAUUAUUGGGAUGUC8078
54790_3_1355−chr4: 105239916-105239936UUGUGUUGUUAUAACUUUAA8079
54790_3_1360−chr4: 105239955-105239975ACCCGAGAGAGGGAGAGGGA8080
54790_3_1361−chr4: 105239956-105239976AACCCGAGAGAGGGAGAGGG8081
54790_3_1363−chr4: 105239974-105239994CGAGAUAGUUGGUCGGCAAA8082
54790_3_1364−chr4: 105239975-105239995ACGAGAUAGUUGGUCGGCAA8083
54790_3_1368−chr4: 105240036-105240056GCAUGGGUAUUAGACCAUUU8084
54790_3_1369−chr4: 105240043-105240063GUGUUUGGCAUGGGUAUUAG8085
54790_3_1376−chr4: 105240069-105240089AAUGAUAAGAUUAAAAACCC8086
54790_3_1379−chr4: 105240070-105240090CAAUGAUAAGAUUAAAAACC8087
54790_3_1381−chr4: 105240071-105240091ACAAUGAUAAGAUUAAAAAC8088
54790_3_1382−chr4: 105240072-105240092UACAAUGAUAAGAUUAAAAA8089
54790_3_1384−chr4: 105240073-105240093CUACAAUGAUAAGAUUAAAA8090
54790_3_1396−chr4: 105240118-105240138CAAAUAAUAAUAAAUACAAU8091
54790_3_1403−chr4: 105240162-105240182GUACAGAGACAUAGUGUAAA8092
54790_3_1416−chr4: 105240245-105240265AAAAUGUUUGACUUCCAAAC8093
54790_3_1418−chr4: 105240252-105240272GACACUGAAAAUGUUUGACU8094
54790_3_1437−chr4: 105240320-105240340AAAGCUUUUUUUAAAAAUAG8095
54790_3_1458−chr4: 105240511-105240531AGGGAAAACAUGGCACGGGU8096
54790_3_1460−chr4: 105240515-105240535CAAGAGGGAAAACAUGGCAC8097
54790_3_1461−chr4: 105240516-105240536GCAAGAGGGAAAACAUGGCA8098
54790_3_1463−chr4: 105240521-105240541UCAUUGCAAGAGGGAAAACA8099
54790_3_1465−chr4: 105240530-105240550UGGGGUAUCUCAUUGCAAGA8100
54790_3_1467−chr4: 105240531-105240551GUGGGGUAUCUCAUUGCAAG8101
54790_3_1471−chr4: 105240548-105240568CCAUCCUUCUACACAGUGUG8102
54790_3_1472−chr4: 105240549-105240569UCCAUCCUUCUACACAGUGU8103
54790_3_1473−chr4: 105240550-105240570CUCCAUCCUUCUACACAGUG8104
54790_3_1476−chr4: 105240581-105240601CACACGCAAAGAGGGACAGU8105
54790_3_1480−chr4: 105240589-105240609UUAAUAACCACACGCAAAGA8106
54790_3_1481−chr4: 105240590-105240610CUUAAUAACCACACGCAAAG8107
54790_3_1488−chr4: 105240616-105240636UGUGGUGUUUUAGCCCAGUG8108
54790_3_1491−chr4: 105240634-105240654AAUAUUAUCUAUGAGAUGUG8109
54790_3_1500−chr4: 105240693-105240713AAAAGUGGGAAGAUAGGGGU8110
54790_3_1501−chr4: 105240694-105240714GAAAAGUGGGAAGAUAGGGG8111
54790_3_1503−chr4: 105240697-105240717AUGGAAAAGUGGGAAGAUAG8112
54790_3_1504−chr4: 105240698-105240718GAUGGAAAAGUGGGAAGAUA8113
54790_3_1505−chr4: 105240699-105240719AGAUGGAAAAGUGGGAAGAU8114
54790_3_1509−chr4: 105240707-105240727ACCAACAAAGAUGGAAAAGU8115
54790_3_1512−chr4: 105240708-105240728AACCAACAAAGAUGGAAAAG8116
54790_3_1514−chr4: 105240716-105240736CUGUUGCAAACCAACAAAGA8117
54790_3_1517−chr4: 105240739-105240759GAGAGUCAGGCAAAAAGAAG8118
54790_3_1518−chr4: 105240740-105240760GGAGAGUCAGGCAAAAAGAA8119
54790_3_1519−chr4: 105240741-105240761UGGAGAGUCAGGCAAAAAGA8120
54790_3_1524−chr4: 105240752-105240772AGAGAAAAUCCUGGAGAGUC8121
54790_3_1529−chr4: 105240761-105240781UUUAUGAUGAGAGAAAAUCC8122
54790_3_1557−chr4: 105240882-105240902UAUUGCUUGGUUUAUUGUCA8123
54790_3_1559−chr4: 105240895-105240915CCCACCCCCAGAAUAUUGCU8124
54790_3_1569−chr4: 105240954-105240974CUGGAAGCCUACCUAUUACU8125
54790_3_1574−chr4: 105240973-105240993AAAAAACAUUUAAAGCUAAC8126
54790_3_1581−chr4: 105241000-105241020UACAAUCCAAUUUUUUGAGC8127
54790_3_1588−chr4: 105241052-105241072CUAAACAAAGAAUACAGUGA8128
54790_3_1591−chr4: 105241053-105241073ACUAAACAAAGAAUACAGUG8129
54790_3_1603−chr4: 105241107-105241127AUAUAUUACAUUUCAGAUAU8130
54790_3_1605−chr4: 105241108-105241128AAUAUAUUACAUUUCAGAUA8131
54790_3_1610−chr4: 105241136-105241156UAUAUGUACAUGCUGGUUGU8132
54790_3_1612−chr4: 105241143-105241163AAUUAAGUAUAUGUACAUGC8133
54790_3_1623−chr4: 105241193-105241213CUUUAAAAUGAGUAGAUUGA8134
54790_3_1633−chr4: 105241245-105241265AACCCCCAACUACACAUUAA8135
54790_3_1634−chr4: 105241246-105241266UAACCCCCAACUACACAUUA8136
54790_3_1637−chr4: 105241285-105241305CUCAAUUAUACUAAAUAUAA8137
54790_4_1+chr4: 105241422-105241442AAGAAAGGUAAUUAACGCAA8138
54790_4_3+chr4: 105241428-105241448GGUAAUUAACGCAAAGGCAC8139
54790_4_4+chr4: 105241429-105241449GUAAUUAACGCAAAGGCACA8140
54790_4_21+chr4: 105241523-105241543UAAAUUGAGUAAUUAUUAGU8141
54790_4_25+chr4: 105241538-105241558UUAGUAGGCUUAGCUAUUCU8142
54790_4_26+chr4: 105241539-105241559UAGUAGGCUUAGCUAUUCUA8143
54790_4_35+chr4: 105241592-105241612AGAGAGUCACAAUAUUUGAC8144
54790_4_38+chr4: 105241612-105241632AGGACUAAUAGUCUGCUAGC8145
54790_4_39+chr4: 105241618-105241638AAUAGUCUGCUAGCUGGCAC8146
54790_4_41+chr4: 105241636-105241656ACAGGCUGCCCACUUUGCGA8147
54790_4_45+chr4: 105241653-105241673CGAUGGAUGCCAGAAAACCC8148
54790_4_50+chr4: 105241663-105241683CAGAAAACCCAGGCAUGAAC8149
54790_4_51+chr4: 105241669-105241689ACCCAGGCAUGAACAGGAAU8150
54790_4_52+chr4: 105241678-105241698UGAACAGGAAUCGGCCAGCC8151
54790_4_53+chr4: 105241693-105241713CAGCCAGGCUGCCAGCCACA8152
54790_4_54+chr4: 105241699-105241719GGCUGCCAGCCACAAGGUAC8153
54790_4_55+chr4: 105241705-105241725CAGCCACAAGGUACUGGCAC8154
54790_4_58+chr4: 105241718-105241738CUGGCACAGGCUCCAACGAG8155
54790_4_59+chr4: 105241729-105241749UCCAACGAGAGGUCCCACUC8156
54790_4_64+chr4: 105241770-105241790AAGUGUCAAAGCAGAAAGAC8157
54790_4_65+chr4: 105241780-105241800GCAGAAAGACUGGUAAAGUG8158
54790_4_98+chr4: 105241946-105241966UUUUUUUCGCUAUCAAUCAC8159
54790_4_115+chr4: 105242012-105242032UGAGCGAGAUAAUGCAGAGA8160
54790_4_123+chr4: 105242057-105242077CUCUGAGCUGUUCUUCUUCU8161
54790_4_124+chr4: 105242058-105242078UCUGAGCUGUUCUUCUUCUA8162
54790_4_129+chr4: 105242076-105242096UAGGGUGCCUUUUCAUUAAG8163
54790_4_130+chr4: 105242080-105242100GUGCCUUUUCAUUAAGAGGU8164
54790_4_136+chr4: 105242105-105242125GUAUUAUUAUUAAAGUACUU8165
54790_4_141+chr4: 105242114-105242134UUAAAGUACUUAGGAUACAU8166
54790_4_142+chr4: 105242115-105242135UAAAGUACUUAGGAUACAUU8167
54790_4_143+chr4: 105242116-105242136AAAGUACUUAGGAUACAUUG8168
54790_4_146+chr4: 105242124-105242144UAGGAUACAUUGGGGCAGCU8169
54790_4_160+chr4: 105242210-105242230UUCACUAAAUAAUCAUCUAG8170
54790_4_162+chr4: 105242215-105242235UAAAUAAUCAUCUAGUGGCC8171
54790_4_182+chr4: 105242287-105242307UUGUUUUUUAAACAAGCAGU8172
54790_4_186+chr4: 105242290-105242310UUUUUUAAACAAGCAGUAGG8173
54790_4_192+chr4: 105242298-105242318ACAAGCAGUAGGUGGUGCUU8174
54790_4_194+chr4: 105242306-105242326UAGGUGGUGCUUUGGUCAUA8175
54790_4_197+chr4: 105242307-105242327AGGUGGUGCUUUGGUCAUAA8176
54790_4_201+chr4: 105242328-105242348GGAAGAUAUAGUCUAUUUCU8177
54790_4_204+chr4: 105242351-105242371ACUAUUCCAUAUUUUCCAUG8178
54790_4_206+chr4: 105242355-105242375UUCCAUAUUUUCCAUGUGGC8179
54790_4_215+chr4: 105242404-105242424UCUAAAUUGUGAGACAUUCU8180
54790_4_221+chr4: 105242407-105242427AAAUUGUGAGACAUUCUUGG8181
54790_4_229+chr4: 105242469-105242489UAAAAUAGCUAAAUUUAGUA8182
54790_4_233+chr4: 105242470-105242490AAAAUAGCUAAAUUUAGUAA8183
54790_4_270+chr4: 105242625-105242645AUCUGUACAUUUUGAUAUUG8184
54790_4_272+chr4: 105242635-105242655UUUGAUAUUGAGGAAAAACA8185
54790_4_278+chr4: 105242663-105242683AAACCAUUAUCCAGUUUGCU8186
54790_4_286+chr4: 105242705-105242725UAAUAAACCGUUCAUUUCUC8187
54790_4_287+chr4: 105242711-105242731ACCGUUCAUUUCUCAGGAUG8188
54790_4_308−chr4: 105241470-105241490AAAAUUCUGACAUAUACAAA8189
54790_4_315−chr4: 105241494-105241514ACUGCUUUGUGUGUGAAGGC8190
54790_4_318−chr4: 105241498-105241518GUUUACUGCUUUGUGUGUGA8191
54790_4_325−chr4: 105241568-105241588AAUAGCACAGUGUGUAGUGU8192
54790_4_328−chr4: 105241593-105241613UGUCAAAUAUUGUGACUCUC8193
54790_4_333−chr4: 105241647-105241667UCUGGCAUCCAUCGCAAAGU8194
54790_4_334−chr4: 105241648-105241668UUCUGGCAUCCAUCGCAAAG8195
54790_4_338−chr4: 105241665-105241685CUGUUCAUGCCUGGGUUUUC8196
54790_4_339−chr4: 105241673-105241693GCCGAUUCCUGUUCAUGCCU8197
54790_4_340−chr4: 105241674-105241694GGCCGAUUCCUGUUCAUGCC8198
54790_4_343−chr4: 105241695-105241715CUUGUGGCUGGCAGCCUGGC8199
54790_4_344−chr4: 105241699-105241719GUACCUUGUGGCUGGCAGCC8200
54790_4_345−chr4: 105241707-105241727CUGUGCCAGUACCUUGUGGC8201
54790_4_347−chr4: 105241711-105241731GAGCCUGUGCCAGUACCUUG8202
54790_4_348−chr4: 105241733-105241753GCCAGAGUGGGACCUCUCGU8203
54790_4_352−chr4: 105241745-105241765UCAGGUGGGAAAGCCAGAGU8204
54790_4_355−chr4: 105241746-105241766AUCAGGUGGGAAAGCCAGAG8205
54790_4_361−chr4: 105241759-105241779UUGACACUUUAUUAUCAGGU8206
54790_4_363−chr4: 105241760-105241780UUUGACACUUUAUUAUCAGG8207
54790_4_368−chr4: 105241763-105241783UGCUUUGACACUUUAUUAUC8208
54790_4_379−chr4: 105241819-105241839ACUAGGUGAAUUUAAUUCAG8209
54790_4_383−chr4: 105241836-105241856AAGUACUCAUUUGCAACACU8210
54790_4_392−chr4: 105241878-105241898UCACACUUGCUCUCUUUUUA8211
54790_4_399−chr4: 105241939-105241959AUAGCGAAAAAAAAAAAAAA8212
54790_4_403−chr4: 105241986-105242006UCUUCUACAUGCAGGAGUAA8213
54790_4_405−chr4: 105241994-105242014CAUAAGAGUCUUCUACAUGC8214
54790_4_412−chr4: 105242038-105242058GCUGUAUAAAUUUAUAUGAA8215
54790_4_422−chr4: 105242086-105242106CUGCCUACCUCUUAAUGAAA8216
54790_4_433−chr4: 105242173-105242193AGAAAUGAAUAAUUUGGAAA8217
54790_4_436−chr4: 105242179-105242199UAAUUUAGAAAUGAAUAAUU8218
54790_4_449−chr4: 105242236-105242256GGAAAUUCACUAUUUCUGCC8219
54790_4_450−chr4: 105242257-105242277GUUGUUUUUUUUGGCACUUA8220
54790_4_452−chr4: 105242258-105242278UGUUGUUUUUUUUGGCACUU8221
54790_4_455−chr4: 105242266-105242286UGUUUUUUUGUUGUUUUUUU8222
54790_4_464−chr4: 105242360-105242380AUCCAGCCACAUGGAAAAUA8223
54790_4_466−chr4: 105242369-105242389AUAGUUAGUAUCCAGCCACA8224
54790_4_471−chr4: 105242395-105242415CACAAUUUAGAAAAGGAGGC8225
54790_4_472−chr4: 105242399-105242419GUCUCACAAUUUAGAAAAGG8226
54790_4_474−chr4: 105242402-105242422AAUGUCUCACAAUUUAGAAA8227
54790_4_491−chr4: 105242462-105242482UUUAGCUAUUUUAAAACUUG8228
54790_4_493−chr4: 105242463-105242483AUUUAGCUAUUUUAAAACUU8229
54790_4_496−chr4: 105242464-105242484AAUUUAGCUAUUUUAAAACU8230
54790_4_512−chr4: 105242539-105242559UUUCACAAAGCACAAAAUUC8231
54790_4_518−chr4: 105242583-105242603AAUUACAUGUGGGUGAAAAU8232
54790_4_520−chr4: 105242584-105242604AAAUUACAUGUGGGUGAAAA8233
54790_4_525−chr4: 105242593-105242613CUAUUUUGUAAAUUACAUGU8234
54790_4_526−chr4: 105242594-105242614ACUAUUUUGUAAAUUACAUG8235
54790_4_539−chr4: 105242669-105242689ACGCCAAGCAAACUGGAUAA8236
54790_4_541−chr4: 105242676-105242696CAGGUCUACGCCAAGCAAAC8237
54790_4_550−chr4: 105242695-105242715CGGUUUAUUAUUUUUUAAAC8238
54790_4_551−chr4: 105242715-105242735ACCACAUCCUGAGAAAUGAA8239
54790_4_566−chr4: 105242780-105242800AAUUAGCAAAUGAAUUCAAG8240
54790_5_2+chr4: 105242931-105242951GUGUGACUUGAUAAAGCCUU8241
54790_5_5+chr4: 105242944-105242964AAGCCUUUGGUCUUAAAUCU8242
54790_5_6+chr4: 105242945-105242965AGCCUUUGGUCUUAAAUCUU8243
54790_5_18+chr4: 105242979-105242999GUAAAUCUGACCCUGAGAAU8244
54790_5_20+chr4: 105242980-105243000UAAAUCUGACCCUGAGAAUU8245
54790_5_34+chr4: 105243059-105243079AUGUGUUAUCUCUUAAGAAG8246
54790_5_45+chr4: 105243115-105243135AUUGAAAUAAUUUAGUGAUG8247
54790_5_49+chr4: 105243121-105243141AUAAUUUAGUGAUGAGGAAG8248
54790_5_73+chr4: 105243263-105243283AUGUAUCUUUCAUCUAGCUC8249
54790_5_77+chr4: 105243275-105243295UCUAGCUCUGGUUUUAAUGC8250
54790_5_82+chr4: 105243303-105243323UUUAAUUGUCCCCACUGUAC8251
54790_5_83+chr4: 105243304-105243324UUAAUUGUCCCCACUGUACU8252
54790_5_89+chr4: 105243326-105243346GUAUAGUCUGCUAAACAUUA8253
54790_5_95+chr4: 105243361-105243381UCUCUCCUUGUUCUGAUACU8254
54790_5_96+chr4: 105243362-105243382CUCUCCUUGUUCUGAUACUA8255
54790_5_100+chr4: 105243386-105243406CAAAGCCCACUUUUUAUAGA8256
54790_5_101+chr4: 105243387-105243407AAAGCCCACUUUUUAUAGAU8257
54790_5_102+chr4: 105243397-105243417UUUUAUAGAUGGGCAGCAAA8258
54790_5_108+chr4: 105243405-105243425AUGGGCAGCAAAAGGCACAU8259
54790_5_113+chr4: 105243504-105243524AAGUGACCCUUGUUUUGUUU8260
54790_5_116+chr4: 105243508-105243528GACCCUUGUUUUGUUUUGGU8261
54790_5_117+chr4: 105243509-105243529ACCCUUGUUUUGUUUUGGUU8262
54790_5_118+chr4: 105243510-105243530CCCUUGUUUUGUUUUGGUUG8263
54790_5_121+chr4: 105243513-105243533UUGUUUUGUUUUGGUUGGGG8264
54790_5_122+chr4: 105243514-105243534UGUUUUGUUUUGGUUGGGGU8265
54790_5_124+chr4: 105243515-105243535GUUUUGUUUUGGUUGGGGUG8266
54790_5_126+chr4: 105243516-105243536UUUUGUUUUGGUUGGGGUGG8267
54790_5_128+chr4: 105243517-105243537UUUGUUUUGGUUGGGGUGGG8268
54790_5_133+chr4: 105243524-105243544UGGUUGGGGUGGGGGGUGUU8269
54790_5_136+chr4: 105243525-105243545GGUUGGGGUGGGGGGUGUUU8270
54790_5_141+chr4: 105243529-105243549GGGGUGGGGGGUGUUUGGGA8271
54790_5_143−chr4: 105242915-105242935ACACUUACCCACUUAGCAAU8272
54790_5_148−chr4: 105242950-105242970UGCCCAAGAUUUAAGACCAA8273
54790_5_154−chr4: 105242992-105243012UCUGGGUAACCCAAUUCUCA8274
54790_5_155−chr4: 105242993-105243013AUCUGGGUAACCCAAUUCUC8275
54790_5_159−chr4: 105243009-105243029CUGGCAUGAGUCUUUGAUCU8276
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54790_5_166−chr4: 105243028-105243048CAGGUAAUGUUCUUUUUAAC8278
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54790_6_3479+chr4: 105258830-105258850CAUUAGAAUGUAUCAAACUA8772
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54790_6_3505+chr4: 105258983-105259003ACUACAUGCAGUGAUUUGGA8778
54790_6_3509+chr4: 105259001-105259021GAUGGAUAUCCCAAACAUAA8779
54790_6_3514+chr4: 105259073-105259093UAUAUAUCAAGUAUAAAAGU8780
54790_6_3515+chr4: 105259092-105259112UAGGCAAAACAAGCUACUGA8781
54790_6_3516+chr4: 105259095-105259115GCAAAACAAGCUACUGAUGG8782
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54790_6_3522+chr4: 105259126-105259146UAUAGUUCCAGCUAUUUGGG8785
54790_6_3524+chr4: 105259132-105259152UCCAGCUAUUUGGGAGGCUG8786
54790_6_3527+chr4: 105259135-105259155AGCUAUUUGGGAGGCUGAGG8787
54790_6_3530+chr4: 105259136-105259156GCUAUUUGGGAGGCUGAGGC8788
54790_6_3535+chr4: 105259163-105259183UCACUUGAGCCCAGAAGUUC8789
54790_6_3542+chr4: 105259229-105259249AGCAUUAUUAACAUAAAAAU8790
54790_6_3550+chr4: 105259265-105259285UUCUUAGAGAAGUUACUGUU8791
54790_6_3552+chr4: 105259266-105259286UCUUAGAGAAGUUACUGUUA8792
54790_6_3559+chr4: 105259291-105259311ACAGACAGUGAGUGACUGAA8793
54790_6_3562+chr4: 105259301-105259321AGUGACUGAAAGGCAAAAUG8794
54790_6_3564+chr4: 105259302-105259322GUGACUGAAAGGCAAAAUGA8795
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54790_6_3572+chr4: 105259314-105259334CAAAAUGAGGGGAAAUUCCA8798
54790_6_3573+chr4: 105259315-105259335AAAAUGAGGGGAAAUUCCAG8799
54790_6_3576+chr4: 105259343-105259363AAAUAUUUUGUUUCUUAGUG8800
54790_6_3577+chr4: 105259344-105259364AAUAUUUUGUUUCUUAGUGU8801
54790_6_3584+chr4: 105259358-105259378UAGUGUGGGUUCUACUUAAC8802
54790_6_3585+chr4: 105259359-105259379AGUGUGGGUUCUACUUAACU8803
54790_6_3604+chr4: 105259461-105259481AAUUGAAAUAGUUCUGUGUG8804
54790_6_3620+chr4: 105259579-105259599GCUAUCCAUAGCAAUGAAUU8805
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54790_6_3625−chr4: 105243798-105243818AGUGGCCGCAAAGAGGGGAG8809
54790_6_3630−chr4: 105243803-105243823CUAUCAGUGGCCGCAAAGAG8810
54790_6_3632−chr4: 105243804-105243824CCUAUCAGUGGCCGCAAAGA8811
54790_6_3633−chr4: 105243805-105243825UCCUAUCAGUGGCCGCAAAG8812
54790_6_3638−chr4: 105243816-105243836AGAUUGGGCUUUCCUAUCAG8813
54790_6_3642−chr4: 105243831-105243851CUUCCUUUCAACCAAAGAUU8814
54790_6_3643−chr4: 105243832-105243852UCUUCCUUUCAACCAAAGAU8815
54790_6_3654−chr4: 105243900-105243920UUAUCGCAUGACUGCCAAAC8816
54790_6_3661−chr4: 105243986-105244006CUCUGACUGCUCCUAAUUAA8817
54790_6_3665−chr4: 105244018-105244038AUGGUAUAACUGAGGCCAUG8818
54790_6_3668−chr4: 105244026-105244046UCAAGUUUAUGGUAUAACUG8819
54790_6_3670−chr4: 105244037-105244057CAUAAACAAUUUCAAGUUUA8820
54790_6_3674−chr4: 105244085-105244105AAUAUAGUGGCCAGGCACAC8821
54790_6_3676−chr4: 105244093-105244113UACAUACUAAUAUAGUGGCC8822
54790_6_3677−chr4: 105244098-105244118GUCAAUACAUACUAAUAUAG8823
54790_6_3681−chr4: 105244122-105244142CAGAUACUGCAACAUGGAAG8824
54790_6_3685−chr4: 105244128-105244148CUGUUUCAGAUACUGCAACA8825
54790_6_3694−chr4: 105244181-105244201AUAUGGAAGGUAUUUGACCU8826
54790_6_3697−chr4: 105244182-105244202CAUAUGGAAGGUAUUUGACC8827
54790_6_3706−chr4: 105244194-105244214UUUUGCUACAUACAUAUGGA8828
54790_6_3707−chr4: 105244198-105244218UUGUUUUUGCUACAUACAUA8829
54790_6_3716−chr4: 105244230-105244250UCUAUUUCUACAGAACUUCU8830
54790_6_3729−chr4: 105244289-105244309AGCAGUUUUGAUUACUAUUG8831
54790_6_3743−chr4: 105244371-105244391AUUCUAAAUUCUUAUAUUCC8832
54790_6_3752−chr4: 105244433-105244453UAAAACAAAACAUUAGCAAC8833
54790_6_3757−chr4: 105244460-105244480UAGACUUCAUGCAAAGUGGA8834
54790_6_3758−chr4: 105244464-105244484GGUUUAGACUUCAUGCAAAG8835
54790_6_3764−chr4: 105244485-105244505AUGAGGCUUUUUCCAACUGA8836
54790_6_3767−chr4: 105244502-105244522GUAGAGGAAUAUUAAAAAUG8837
54790_6_3772−chr4: 105244518-105244538CAGGAUUAUCAGCACAGUAG8838
54790_6_3780−chr4: 105244537-105244557CUAUUCUUUUAGUGUUAUAC8839
54790_6_3788−chr4: 105244638-105244658CGCGGUAACGUGAGGUCGGA8840
54790_6_3789−chr4: 105244639-105244659GCGCGGUAACGUGAGGUCGG8841
54790_6_3793−chr4: 105244673-105244693UUGGACCCUCCACCUCCAGC8842
54790_6_3794−chr4: 105244679-105244699GAGAACUUGGACCCUCCACC8843
54790_6_3795−chr4: 105244682-105244702UUAGAGAACUUGGACCCUCC8844
54790_6_3798−chr4: 105244685-105244705CUCUUAGAGAACUUGGACCC8845
54790_6_3799−chr4: 105244688-105244708GUCCUCUUAGAGAACUUGGA8846
54790_6_3801−chr4: 105244689-105244709CGUCCUCUUAGAGAACUUGG8847
54790_6_3807−chr4: 105244707-105244727CGAUGAUCCCUCCGACUCCG8848
54790_6_3809−chr4: 105244711-105244731GGGUCGAUGAUCCCUCCGAC8849
54790_6_3811−chr4: 105244717-105244737ACAUUAGGGUCGAUGAUCCC8850
54790_6_3813−chr4: 105244720-105244740CGGACAUUAGGGUCGAUGAU8851
54790_6_3814−chr4: 105244721-105244741ACGGACAUUAGGGUCGAUGA8852
54790_6_3818−chr4: 105244748-105244768UGUUUUAAUCGGCCCACACC8853
54790_6_3819−chr4: 105244751-105244771UUAUGUUUUAAUCGGCCCAC8854
54790_6_3820−chr4: 105244756-105244776GAUUUUUAUGUUUUAAUCGG8855
54790_6_3821−chr4: 105244757-105244777UGAUUUUUAUGUUUUAAUCG8856
54790_6_3826−chr4: 105244795-105244815GCUCUGGUCGGACUGGUUGU8857
54790_6_3829−chr4: 105244822-105244842CACCCGUUAGUGGACUCCAG8858
54790_6_3831−chr4: 105244823-105244843CCACCCGUUAGUGGACUCCA8859
54790_6_3834−chr4: 105244827-105244847GGCUCCACCCGUUAGUGGAC8860
54790_6_3838−chr4: 105244840-105244860CGUGAAACCCUCCGGCUCCA8861
54790_6_3839−chr4: 105244841-105244861CCGUGAAACCCUCCGGCUCC8862
54790_6_3841−chr4: 105244844-105244864AUUCCGUGAAACCCUCCGGC8863
54790_6_3843−chr4: 105244850-105244870ACGGACAUUCCGUGAAACCC8864
54790_6_3844−chr4: 105244853-105244873AGUACGGACAUUCCGUGAAA8865
54790_6_3846−chr4: 105244854-105244874GAGUACGGACAUUCCGUGAA8866
54790_6_3849−chr4: 105244862-105244882GCGCCGCCGAGUACGGACAU8867
54790_6_3853−chr4: 105244877-105244897AGAUUUCUCCGGUCCGCGCC8868
54790_6_3854−chr4: 105244880-105244900GUAAGAUUUCUCCGGUCCGC8869
54790_6_3855−chr4: 105244885-105244905AACUUGUAAGAUUUCUCCGG8870
54790_6_3856−chr4: 105244890-105244910AAAAUAACUUGUAAGAUUUC8871
54790_6_3862−chr4: 105244914-105244934AUUAUUUUAAAACCAAUCGU8872
54790_6_3863−chr4: 105244915-105244935AAUUAUUUUAAAACCAAUCG8873
54790_6_3865−chr4: 105244955-105244975UGCAGAGAAAAAGACACUAA8874
54790_6_3873−chr4: 105244979-105244999CAAAUGAUUCUAUAGUUUGG8875
54790_6_3875−chr4: 105244982-105245002CAGCAAAUGAUUCUAUAGUU8876
54790_6_3887−chr4: 105245046-105245066UAAACAGCAAAGGACAAAUU8877
54790_6_3889−chr4: 105245056-105245076GUUAGAGUUUUAAACAGCAA8878
54790_6_3919−chr4: 105245219-105245239GGUACACACCAUAAAAUUUU8879
54790_6_3924−chr4: 105245240-105245260AAUCAUUUGUAAAAGUGGUC8880
54790_6_3926−chr4: 105245245-105245265CAAUUAAUCAUUUGUAAAAG8881
54790_6_3941−chr4: 105245373-105245393CGUGGUAACGUGAGGUCGGA8882
54790_6_3942−chr4: 105245374-105245394GCGUGGUAACGUGAGGUCGG8883
54790_6_3949−chr4: 105245414-105245434ACGAACUUGGGUCCUCUACC8884
54790_6_3950−chr4: 105245417-105245437UUAACGAACUUGGGUCCUCU8885
54790_6_3954−chr4: 105245423-105245443GUCCUCUUAACGAACUUGGG8886
54790_6_3959−chr4: 105245442-105245462CGAUAAGCCCUCCGACUCCG8887
54790_6_3962−chr4: 105245446-105245466GGGUCGAUAAGCCCUCCGAC8888
54790_6_3964−chr4: 105245452-105245472ACAUUAGGGUCGAUAAGCCC8889
54790_6_3966−chr4: 105245455-105245475CGGACAUUAGGGUCGAUAAG8890
54790_6_3967−chr4: 105245456-105245476ACGGACAUUAGGGUCGAUAA8891
54790_6_3971−chr4: 105245486-105245506UUAUGUUUUAAUCGACCCAC8892
54790_6_3972−chr4: 105245491-105245511GAUUUUUAUGUUUUAAUCGA8893
54790_6_3973−chr4: 105245492-105245512UGAUUUUUAUGUUUUAAUCG8894
54790_6_3978−chr4: 105245530-105245550GGUCUGGUCGGACUAGUUGU8895
54790_6_3980−chr4: 105245557-105245577GCCCGCCUAGUGGGCUCCAG8896
54790_6_3983−chr4: 105245562-105245582GCUCCGCCCGCCUAGUGGGC8897
54790_6_3985−chr4: 105245573-105245593GAGACCCUCCGGCUCCGCCC8898
54790_6_3987−chr4: 105245576-105245596CGUGAGACCCUCCGGCUCCG8899
54790_6_3988−chr4: 105245577-105245597UCGUGAGACCCUCCGGCUCC8900
54790_6_3990−chr4: 105245580-105245600GGGUCGUGAGACCCUCCGGC8901
54790_6_3992−chr4: 105245586-105245606ACAUUAGGGUCGUGAGACCC8902
54790_6_3993−chr4: 105245589-105245609CGGACAUUAGGGUCGUGAGA8903
54790_6_3995−chr4: 105245590-105245610ACGGACAUUAGGGUCGUGAG8904
54790_6_4000−chr4: 105245617-105245637AUAUUUCACCGACCCGUGUC8905
54790_6_4002−chr4: 105245625-105245645UUAAAAAAAUAUUUCACCGA8906
54790_6_4003−chr4: 105245626-105245646AUUAAAAAAAUAUUUCACCG8907
54790_6_4005−chr4: 105245630-105245650GUAGAUUAAAAAAAUAUUUC8908
54790_6_4008−chr4: 105245652-105245672AGAAAGAGCAAGAGGAGUCA8909
54790_6_4010−chr4: 105245653-105245673CAGAAAGAGCAAGAGGAGUC8910
54790_6_4015−chr4: 105245660-105245680UUUUCUUCAGAAAGAGCAAG8911
54790_6_4036−chr4: 105245706-105245726UUAAUUUUUUUUCUAAUUAA8912
54790_6_4062−chr4: 105245854-105245874AAAACUAUCAUUUUCACAAG8913
54790_6_4074−chr4: 105245899-105245919AAAAUCAAACAUUUUGCAAU8914
54790_6_4081−chr4: 105245932-105245952AUGAAUGAAAUAUAGUUUCC8915
54790_6_4096−chr4: 105246008-105246028UUGGGCCCUCCACCUCCAAC8916
54790_6_4097−chr4: 105246014-105246034GUGAACUUGGGCCCUCCACC8917
54790_6_4099−chr4: 105246017-105246037UUAGUGAACUUGGGCCCUCC8918
54790_6_4101−chr4: 105246020-105246040CUCUUAGUGAACUUGGGCCC8919
54790_6_4103−chr4: 105246023-105246043GUACUCUUAGUGAACUUGGG8920
54790_6_4104−chr4: 105246024-105246044CGUACUCUUAGUGAACUUGG8921
54790_6_4111−chr4: 105246046-105246066AGAUCGAUGAGCCCUCCGAC8922
54790_6_4112−chr4: 105246052-105246072ACAUUAAGAUCGAUGAGCCC8923
54790_6_4114−chr4: 105246055-105246075CGGACAUUAAGAUCGAUGAG8924
54790_6_4115−chr4: 105246056-105246076ACGGACAUUAAGAUCGAUGA8925
54790_6_4118−chr4: 105246079-105246099UUAUGUUUUUACUCGGCCCA8926
54790_6_4119−chr4: 105246080-105246100UUUAUGUUUUUACUCGGCCC8927
54790_6_4121−chr4: 105246083-105246103AUUUUUAUGUUUUUACUCGG8928
54790_6_4122−chr4: 105246084-105246104GAUUUUUAUGUUUUUACUCG8929
54790_6_4127−chr4: 105246123-105246143GCUCUAGUUAGACCGGUUGU8930
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54790_6_4131−chr4: 105246150-105246170ACCCACCCAAUGGACUUCGG8932
54790_6_4137−chr4: 105246165-105246185AAACCCUCCGGUCCCACCCA8933
54790_6_4138−chr4: 105246166-105246186GAAACCCUCCGGUCCCACCC8934
54790_6_4140−chr4: 105246169-105246189CGUGAAACCCUCCGGUCCCA8935
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54790_6_4143−chr4: 105246173-105246193GGGUCGUGAAACCCUCCGGU8937
54790_6_4144−chr4: 105246174-105246194AGGGUCGUGAAACCCUCCGG8938
54790_6_4146−chr4: 105246179-105246199ACAUUAGGGUCGUGAAACCC8939
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54790_6_4150−chr4: 105246183-105246203GUGGACAUUAGGGUCGUGAA8941
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54790_6_4154−chr4: 105246213-105246233AUGGAAAAGCUCCGACCCGU8943
54790_6_4155−chr4: 105246218-105246238GAAUUAUGGAAAAGCUCCGA8944
54790_6_4158−chr4: 105246219-105246239AGAAUUAUGGAAAAGCUCCG8945
54790_6_4160−chr4: 105246223-105246243UAUAAGAAUUAUGGAAAAGC8946
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54790_6_4169−chr4: 105246250-105246270UCAGAUUCCAUUUCAGGCAU8948
54790_6_4175−chr4: 105246256-105246276UAUAUGUCAGAUUCCAUUUC8949
54790_6_4185−chr4: 105246320-105246340UCUGGUCCAACUAUUUUUCA8950
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54790_6_4230−chr4: 105246543-105246563AGUAUUAAAAUUUUUUAUUU8952
54790_6_4239−chr4: 105246594-105246614AGUAAAGUCUGUAUUGACAU8953
54790_6_4248−chr4: 105246644-105246664UAAAAUAAAAUCUAUUUAUG8954
54790_6_4249−chr4: 105246645-105246665AUAAAAUAAAAUCUAUUUAU8955
54790_6_4251−chr4: 105246646-105246666CAUAAAAUAAAAUCUAUUUA8956
54790_6_4266−chr4: 105246699-105246719AUUAUUCUAUUCUCUGUUCU8957
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54790_6_4281−chr4: 105246793-105246813GUUUGGAGCAUGUGGACACA8959
54790_6_4282−chr4: 105246794-105246814GGUUUGGAGCAUGUGGACAC8960
54790_6_4285−chr4: 105246801-105246821AGUGGGUGGUUUGGAGCAUG8961
54790_6_4291−chr4: 105246810-105246830UGAACUCACAGUGGGUGGUU8962
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54790_6_4295−chr4: 105246818-105246838UUCUUUUCUGAACUCACAGU8964
54790_6_4296−chr4: 105246819-105246839GUUCUUUUCUGAACUCACAG8965
54790_6_4309−chr4: 105246889-105246909AAACAGCUGGUUUGGCUCAA8966
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54790_6_4315−chr4: 105246902-105246922AUCUUUAAAGAAGAAACAGC8968
54790_6_4321−chr4: 105246927-105246947CAUAAAAUGGAAAUCUCAAA8969
54790_6_4322−chr4: 105246928-105246948UCAUAAAAUGGAAAUCUCAA8970
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54790_6_4331−chr4: 105246961-105246981CUUACUUGCCAAAAAAAUAC8972
54790_6_4339−chr4: 105247023-105247043ACCAUGGCAGAAGGCAUUUC8973
54790_6_4342−chr4: 105247032-105247052ACAUCACCCACCAUGGCAGA8974
54790_6_4346−chr4: 105247039-105247059AUGUUUAACAUCACCCACCA8975
54790_6_4365−chr4: 105247125-105247145CUACGACACACUACCCAGGU8976
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54790_6_4370−chr4: 105247133-105247153AUUUAUAACUACGACACACU8978
54790_6_4376−chr4: 105247190-105247210UGUGAUCACCCUCACCUACA8979
54790_6_4379−chr4: 105247191-105247211UUGUGAUCACCCUCACCUAC8980
54790_6_4382−chr4: 105247197-105247217GAAAGUUUGUGAUCACCCUC8981
54790_6_4385−chr4: 105247202-105247222AAGACGAAAGUUUGUGAUCA8982
54790_6_4386−chr4: 105247203-105247223GAAGACGAAAGUUUGUGAUC8983
54790_6_4391−chr4: 105247238-105247258ACUUUACAAUUGUCCAUUCU8984
54790_6_4392−chr4: 105247246-105247266UAUGUAGGACUUUACAAUUG8985
54790_6_4420−chr4: 105247387-105247407CUUCACAGUUAGUACACCUU8986
54790_6_4421−chr4: 105247388-105247408UCUUCACAGUUAGUACACCU8987
54790_6_4424−chr4: 105247392-105247412UGAGUCUUCACAGUUAGUAC8988
54790_6_4428−chr4: 105247423-105247443GGUCUGUUACCUGUACUUGA8989
54790_6_4430−chr4: 105247424-105247444GGGUCUGUUACCUGUACUUG8990
54790_6_4438−chr4: 105247435-105247455AAUUAUCGAUAGGGUCUGUU8991
54790_6_4444−chr4: 105247467-105247487UUACCUCUCUUAAAAUACUC8992
54790_6_4454−chr4: 105247485-105247505GUGUCUUAAAUAGAAGAUUU8993
54790_6_4460−chr4: 105247517-105247537CCCGAUAAUAUUUAUUUUUC8994
54790_6_4464−chr4: 105247537-105247557UUAAGUAUUUCUUUCCCCUU8995
54790_6_4465−chr4: 105247538-105247558UUUAAGUAUUUCUUUCCCCU8996
54790_6_4468−chr4: 105247542-105247562UAAGUUUAAGUAUUUCUUUC8997
54790_6_4470−chr4: 105247543-105247563UUAAGUUUAAGUAUUUCUUU8998
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54790_6_4853−chr4: 105249281-105249301ACAUUAGGGUCGUGAAAUCC9099
54790_6_4855−chr4: 105249284-105249304CGAACAUUAGGGUCGUGAAA9100
54790_6_4857−chr4: 105249312-105249332CUUUUACACCGACCCGUGUC9101
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54790_6_4859−chr4: 105249321-105249341UACCUUUUUCUUUUACACCG9103
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54790_6_4877−chr4: 105249463-105249483AAUGAUUGUUACAGUGAGGA9107
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54790_6_4887−chr4: 105249533-105249553CAUUUUCGUAUUUCGAUGAA9109
54790_6_4894−chr4: 105249563-105249583GACCUUGGAAGUAUGUAACA9110
54790_6_4899−chr4: 105249582-105249602AACUCCUACACCUCUAUGUG9111
54790_6_4903−chr4: 105249593-105249613UAUUGUAAAAGAACUCCUAC9112
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54790_6_4918−chr4: 105249681-105249701CUACGGGUUAUAGUCGGUAA9116
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54790_6_4933−chr4: 105249843-105249863CUUCGCUGUUGGACACCCUA9119
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54790_6_4949−chr4: 105249879-105249899AAAUUUUGAAAACAUGAAAU9122
54790_6_4963−chr4: 105249975-105249995UUAGAAAGUCUAGAACUUAC9123
54790_6_4967−chr4: 105250002-105250022UAUGAGACUCUUCUUUCGUA9124
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54790_6_4989−chr4: 105250122-105250142UGUUUACCACGACUCUUUUG9127
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54790_6_5006−chr4: 105250242-105250262GAUGUCCUUAGUCGUGUCAC9131
54790_6_5012−chr4: 105250258-105250278UUUUAAAUGAUGUUUUGAUG9132
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54790_6_5020−chr4: 105250320-105250340CCUUUGGGUUCUUUGUACCA9134
54790_6_5021−chr4: 105250324-105250344UAUACCUUUGGGUUCUUUGU9135
54790_6_5024−chr4: 105250341-105250361UCGACUAGAAUUUUACGUAU9136
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54790_6_5050−chr4: 105250478-105250498UCGAGAGACCCUUCGGAUCC9144
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54790_6_5101−chr4: 105250692-105250712AAUUUUUUUUAUUUUUCACG9157
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54790_6_5110−chr4: 105250757-105250777CUCCAACGUCACUCGACUCU9161
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54790_6_5432−chr4: 105252445-105252465AUAAGUAUUAACAGUUUUGA9239
54790_6_5444−chr4: 105252518-105252538CGAGACACAAUAAAUGAGUU9240
54790_6_5460−chr4: 105252619-105252639GAAAGACAAACAAGACGUUU9241
54790_6_5474−chr4: 105252718-105252738UGUCUUGUAUAUCUACUGGA9242
54790_6_5479−chr4: 105252749-105252769UACGUCUUGAUAUUUUAAAG9243
54790_6_5488−chr4: 105252791-105252811AACGUUUUAAUUACGUUUUA9244
54790_6_5489−chr4: 105252792-105252812AAACGUUUUAAUUACGUUUU9245
54790_6_5496−chr4: 105252862-105252882UCUUUACCAUGCCCUUGUUG9246
54790_6_5498−chr4: 105252871-105252891AUCAGAAAUUCUUUACCAUG9247
54790_6_5501−chr4: 105252872-105252892UAUCAGAAAUUCUUUACCAU9248
54790_6_5503−chr4: 105252877-105252897GUUUCUAUCAGAAAUUCUUU9249
54790_6_5507−chr4: 105252913-105252933CUAGAAACUGUUUCAUCGUU9250
54790_6_5513−chr4: 105252982-105253002UCAGAUCUGUUUAUAUAGUU9251
54790_6_5519−chr4: 105253009-105253029AAUUGUUCUAUCACACCAUA9252
54790_6_5520−chr4: 105253015-105253035GGAUUCAAUUGUUCUAUCAC9253
54790_6_5523−chr4: 105253073-105253093UUCCUCUUUUUGUUACAGUC9254
54790_6_5528−chr4: 105253092-105253112UUAUCGGUUGAGUUAUGACU9255
54790_6_5539−chr4: 105253121-105253141ACGAAAAAAAUGAAUCAUUA9256
54790_6_5548−chr4: 105253185-105253205UAAAAUUUCAAAUAUAGUUC9257
54790_6_5554−chr4: 105253222-105253242UUUUAAGGACGUUCUAAAAC9258
54790_6_5561−chr4: 105253286-105253306CUUCUACACAUAACAGUUCU9259
54790_6_5564−chr4: 105253308-105253328CUACAAGGUACAAGUACCUA9260
54790_6_5567−chr4: 105253313-105253333UUUCUCUACAAGGUACAAGU9261
54790_6_5572−chr4: 105253345-105253365UUUUACGUUUUAAGAUUACU9262
54790_6_5576−chr4: 105253368-105253388UAUACAUGUACCAGAUAUAC9263
54790_6_5578−chr4: 105253369-105253389UUAUACAUGUACCAGAUAUA9264
54790_6_5579−chr4: 105253370-105253390AUUAUACAUGUACCAGAUAU9265
54790_6_5584−chr4: 105253379-105253399CAUAUUUAGAUUAUACAUGU9266
54790_6_5599−chr4: 105253514-105253534ACUAAUAUAUUGUACCAACG9267
54790_6_5601−chr4: 105253521-105253541AGAUUUCACUAAUAUAUUGU9268
54790_6_5602−chr4: 105253545-105253565UACUGGUUUUUUUUUUUUUG9269
54790_6_5615−chr4: 105253630-105253650GUAAUUCUGUUCUUUUAUUU9270
54790_6_5619−chr4: 105253668-105253688UUACGGAAAGUUGUAGUAUG9271
54790_6_5625−chr4: 105253711-105253731AGGACGACUCUAGUCCUUGU9272
54790_6_5628−chr4: 105253718-105253738CUUCUAAAGGACGACUCUAG9273
54790_6_5638−chr4: 105253841-105253861AGUCAUUUGAUCCUUUUCUC9274
54790_6_5640−chr4: 105253842-105253862GAGUCAUUUGAUCCUUUUCU9275
54790_6_5643−chr4: 105253843-105253863AGAGUCAUUUGAUCCUUUUC9276
54790_6_5650−chr4: 105253851-105253871GUUUUCGGAGAGUCAUUUGA9277
54790_6_5655−chr4: 105253915-105253935GUAUACCAUUAUAGUUAUCC9278
54790_6_5658−chr4: 105253918-105253938UUAGUAUACCAUUAUAGUUA9279
54790_6_5660−chr4: 105253931-105253951AUUCGAUUUCUUUUUAGUAU9280
54790_6_5671−chr4: 105254008-105254028UUGGUACACCCUAAACGAGG9281
54790_6_5672−chr4: 105254020-105254040UAUUACAUAGUGUUGGUACA9282
54790_6_5673−chr4: 105254021-105254041UUAUUACAUAGUGUUGGUAC9283
54790_6_5685−chr4: 105254131-105254151GAAGUAUUGAAUAAGAUACU9284
54790_6_5686−chr4: 105254132-105254152UGAAGUAUUGAAUAAGAUAC9285
54790_6_5705−chr4: 105254208-105254228ACUAAAGAUGGUUUCAAAAU9286
54790_6_5709−chr4: 105254238-105254258UUGUUUCAUGGUCUGUGUCU9287
54790_6_5718−chr4: 105254303-105254323ACGUUUUAUUAUUAGAUUUA9288
54790_6_5721−chr4: 105254345-105254365CUUUACCUGGUUAAGGAACU9289
54790_6_5726−chr4: 105254361-105254381UAAAUUAUUAGUUCCACUUU9290
54790_6_5729−chr4: 105254369-105254389CGGGUGUGUAAAUUAUUAGU9291
54790_6_5733−chr4: 105254420-105254440UCUGGGACAGAGUUUUUGUU9292
54790_6_5737−chr4: 105254454-105254474UAUGAUGACGUGAGGUCGGA9293
54790_6_5738−chr4: 105254455-105254475GUAUGAUGACGUGAGGUCGG9294
54790_6_5743−chr4: 105254495-105254515GUGAACUCGGGUCCUUCAGU9295
54790_6_5745−chr4: 105254504-105254524ACCCAUUUAGUGAACUCGGG9296
54790_6_5749−chr4: 105254523-105254543CGAUGAACCCUCCGACUCCA9297
54790_6_5750−chr4: 105254524-105254544UCGAUGAACCCUCCGACUCC9298
54790_6_5752−chr4: 105254527-105254547GGCUCGAUGAACCCUCCGAC9299
54790_6_5754−chr4: 105254533-105254553ACAUCAGGCUCGAUGAACCC9300
54790_6_5756−chr4: 105254536-105254556CGGACAUCAGGCUCGAUGAA9301
54790_6_5757−chr4: 105254537-105254557ACGGACAUCAGGCUCGAUGA9302
54790_6_5762−chr4: 105254564-105254584UUUUUUAAUCGGUCCGUACC9303
54790_6_5763−chr4: 105254567-105254587UAUUUUUUUAAUCGGUCCGU9304
54790_6_5764−chr4: 105254572-105254592AUUAUUAUUUUUUUAAUCGG9305
54790_6_5766−chr4: 105254611-105254631UUCUGGUGUGACCCGUUGUA9306
54790_6_5769−chr4: 105254620-105254640GUCCUCAAGUUCUGGUGUGA9307
54790_6_5771−chr4: 105254621-105254641GGUCCUCAAGUUCUGGUGUG9308
54790_6_5775−chr4: 105254639-105254659GUCCGUCUAACGAACUCAGG9309
54790_6_5780−chr4: 105254658-105254678GUGAGAAACCUCCGACUCCG9310
54790_6_5781−chr4: 105254662-105254682GGUAGUGAGAAACCUCCGAC9311
54790_6_5783−chr4: 105254668-105254688CGUUAGGGUAGUGAGAAACC9312
54790_6_5784−chr4: 105254671-105254691GGACGUUAGGGUAGUGAGAA9313
54790_6_5788−chr4: 105254700-105254720ACGGUAGUCCGAUCCACACU9314
54790_6_5790−chr4: 105254708-105254728UUUUCAAGACGGUAGUCCGA9315
54790_6_5792−chr4: 105254713-105254733AGGAUUUUUCAAGACGGUAG9316
54790_6_5801−chr4: 105254774-105254794AGUACGAAGGUAUCCUCCUC9317
54790_6_5804−chr4: 105254775-105254795AAGUACGAAGGUAUCCUCCU9318
54790_6_5805−chr4: 105254776-105254796GAAGUACGAAGGUAUCCUCC9319
54790_6_5809−chr4: 105254779-105254799AGGGAAGUACGAAGGUAUCC9320
54790_6_5811−chr4: 105254782-105254802UUUAGGGAAGUACGAAGGUA9321
54790_6_5822−chr4: 105254828-105254848GAUGUAAGUCCUCGGUCUAC9322
54790_6_5828−chr4: 105254840-105254860AAACACUCAAAAGAUGUAAG9323
54790_6_5832−chr4: 105254874-105254894GUUUCCGUAGGUCAGUAUUA9324
54790_6_5834−chr4: 105254891-105254911AAGUCACACUUGUUGAGGUU9325
54790_6_5838−chr4: 105254914-105254934AUAUUAACUACUUAACGACC9326
54790_6_5840−chr4: 105254917-105254937UUUAUAUUAACUACUUAACG9327
54790_6_5845−chr4: 105254948-105254968CAUCCUUGGUCACAACCCUA9328
54790_6_5848−chr4: 105254953-105254973GGAGACAUCCUUGGUCACAA9329
54790_6_5849−chr4: 105254954-105254974UGGAGACAUCCUUGGUCACA9330
54790_6_5854−chr4: 105254966-105254986UGACCUCGUCUUUGGAGACA9331
54790_6_5858−chr4: 105254984-105255004AUUUUUCUUAAUGUCGAAUG9332
54790_6_5862−chr4: 105255008-105255028GAGUGUUGGUUCCUUCGUCU9333
54790_6_5864−chr4: 105255018-105255038UUAGUGACGGGAGUGUUGGU9334
54790_6_5867−chr4: 105255043-105255063CAGUCUCUUUACUCCAGUGU9335
54790_6_5869−chr4: 105255044-105255064ACAGUCUCUUUACUCCAGUG9336
54790_6_5873−chr4: 105255051-105255071AAUCUAGACAGUCUCUUUAC9337
54790_6_5878−chr4: 105255097-105255117UUAGACUUAUAUGGAUGUUG9338
54790_6_5897−chr4: 105255193-105255213GUAUGAGUAUAAAAUAACCU9339
54790_6_5899−chr4: 105255197-105255217AGCUGUAUGAGUAUAAAAUA9340
54790_6_5908−chr4: 105255271-105255291UUUAUAUGAGGAUAUGUCAG9341
54790_6_5912−chr4: 105255297-105255317UUGUUCGUUUAAACCCAUUA9342
54790_6_5914−chr4: 105255304-105255324GUACUUAUUGUUCGUUUAAA9343
54790_6_5915−chr4: 105255305-105255325UGUACUUAUUGUUCGUUUAA9344
54790_6_5924−chr4: 105255410-105255430UGCACUUUGUAAGAGGUCCU9345
54790_6_5926−chr4: 105255414-105255434CGUGUGCACUUUGUAAGAGG9346
54790_6_5933−chr4: 105255498-105255518UUUUUGUGAUAUUUGGUUGA9347
54790_6_5944−chr4: 105255562-105255582AUGAUUAGGUGAAAGUUAUU9348
54790_6_5947−chr4: 105255600-105255620CGUUUUUUACCGUCUUAAUU9349
54790_6_5950−chr4: 105255612-105255632UUUUAUGUACUUCGUUUUUU9350
54790_6_5966−chr4: 105255773-105255793UAUAUUUAACUUUUUAAUUU9351
54790_6_5971−chr4: 105255834-105255854UUCUGUUCUAUGUCUGUUUU9352
54790_6_5978−chr4: 105255899-105255919UUUUUAAAUCAUUUUCUGUU9353
54790_6_5980−chr4: 105255900-105255920UUUUUUAAAUCAUUUUCUGU9354
54790_6_5990−chr4: 105255940-105255960AUUCAAUCAACAUUAGGGGU9355
54790_6_5991−chr4: 105255941-105255961UAUUCAAUCAACAUUAGGGG9356
54790_6_6001−chr4: 105255985-105256005AGGAAUAUAACAUUACUUUA9357
54790_6_6003−chr4: 105256017-105256037UUCUCCCUUACAUCGAUAUA9358
54790_6_6005−chr4: 105256018-105256038UUUCUCCCUUACAUCGAUAU9359
54790_6_6009−chr4: 105256033-105256053UUAUCGUGUCUCAUUUUUCU9360
54790_6_6012−chr4: 105256034-105256054AUUAUCGUGUCUCAUUUUUC9361
54790_6_6018−chr4: 105256080-105256100UUUUGUAUUAGACACAAUUA9362
54790_6_6019−chr4: 105256081-105256101UUUUUGUAUUAGACACAAUU9363
54790_6_6040−chr4: 105256188-105256208UGGUCAUUUCUAUUAAUGUA9364
54790_6_6046−chr4: 105256253-105256273UAUGAAGUCCGACUUUCCUU9365
54790_6_6049−chr4: 105256258-105256278UUACAUAUGAAGUCCGACUU9366
54790_6_6052−chr4: 105256266-105256286UUUAUGAUUUACAUAUGAAG9367
54790_6_6059−chr4: 105256302-105256322UUAUUCUCAAAUAACAAAAG9368
54790_6_6064−chr4: 105256338-105256358UUACAUAAUAUAUUAUUUAA9369
54790_6_6078−chr4: 105256436-105256456GUCUUUGUUACUUCUGGUCU9370
54790_6_6086−chr4: 105256491-105256511ACAUACUAAUAGUACAUACG9371
54790_6_6100−chr4: 105256661-105256681CUUCUUAUAAACUUUUUAUU9372
54790_6_6104−chr4: 105256683-105256703CUCCUACUUCUUAUUUCUUA9373
54790_6_6109−chr4: 105256702-105256722UUACGUCCAGGGGUUUCAUC9374
54790_6_6112−chr4: 105256717-105256737AUGGUUGUAUCUGUAUUACG9375
54790_6_6113−chr4: 105256754-105256774UUGUCUUGGAGUCUCUAGAC9376
54790_6_6128−chr4: 105256827-105256847CAACUUUUCCUCCCCUUUUU9377
54790_6_6129−chr4: 105256828-105256848UCAACUUUUCCUCCCCUUUU9378
54790_6_6134−chr4: 105256835-105256855UAUCGUCUCAACUUUUCCUC9379
54790_6_6136−chr4: 105256836-105256856UUAUCGUCUCAACUUUUCCU9380
54790_6_6138−chr4: 105256837-105256857GUUAUCGUCUCAACUUUUCC9381
54790_6_6141−chr4: 105256840-105256860CAAGUUAUCGUCUCAACUUU9382
54790_6_6146−chr4: 105256862-105256882UUGACGUCAUUUUUAAUCUC9383
54790_6_6147−chr4: 105256863-105256883AUUGACGUCAUUUUUAAUCU9384
54790_6_6149−chr4: 105256864-105256884UAUUGACGUCAUUUUUAAUC9385
54790_6_6172−chr4: 105257041-105257061UUCAGGUCUACAAUCCGGUG9386
54790_6_6175−chr4: 105257048-105257068GGACUUUUUCAGGUCUACAA9387
54790_6_6177−chr4: 105257076-105257096GGGAUAUUUCAUCAGUUAUC9388
54790_6_6180−chr4: 105257100-105257120UCUCUUUGUCUUUGUUUCAU9389
54790_6_6190−chr4: 105257175-105257195AGAGUUGCACGACCCUAAUG9390
54790_6_6193−chr4: 105257183-105257203GAAACCGGAGAGUUGCACGA9391
54790_6_6194−chr4: 105257184-105257204CGAAACCGGAGAGUUGCACG9392
54790_6_6198−chr4: 105257200-105257220GAAUUCACUACGAGGACGAA9393
54790_6_6200−chr4: 105257223-105257243GUCCGAUCAGAACUUGAGGA9394
54790_6_6201−chr4: 105257224-105257244GGUCCGAUCAGAACUUGAGG9395
54790_6_6204−chr4: 105257242-105257262UCCCAGAGUGAUACGACGGG9396
54790_6_6215−chr4: 105257261-105257281AAAAAUAAAAACAUCUCUGU9397
54790_6_6217−chr4: 105257262-105257282UAAAAAUAAAAACAUCUCUG9398
54790_6_6231−chr4: 105257328-105257348UCAUUGUAUAAGACCCGUCC9399
54790_6_6232−chr4: 105257329-105257349GUCAUUGUAUAAGACCCGUC9400
54790_6_6233−chr4: 105257330-105257350UGUCAUUGUAUAAGACCCGU9401
54790_6_6236−chr4: 105257331-105257351UUGUCAUUGUAUAAGACCCG9402
54790_6_6238−chr4: 105257335-105257355GUCUUUGUCAUUGUAUAAGA9403
54790_6_6239−chr4: 105257336-105257356GGUCUUUGUCAUUGUAUAAG9404
54790_6_6246−chr4: 105257388-105257408UCUUUGUUAUGUUUGAAAUA9405
54790_6_6253−chr4: 105257420-105257440AUUGGUUCGUUUCUGAAGCU9406
54790_6_6259−chr4: 105257475-105257495AAUAACUAGAGUCCGUGGAU9407
54790_6_6262−chr4: 105257484-105257504UUCUGACUGAAUAACUAGAG9408
54790_6_6267−chr4: 105257554-105257574UAGGUCUCGACGUUUAUCGG9409
54790_6_6269−chr4: 105257580-105257600AGACGUGUUCGUCCCUUAUU9410
54790_6_6272−chr4: 105257588-105257608GAACUCUGAGACGUGUUCGU9411
54790_6_6273−chr4: 105257589-105257609GGAACUCUGAGACGUGUUCG9412
54790_6_6280−chr4: 105257657-105257677CUUUCGGUGUACGUUGACAU9413
54790_6_6281−chr4: 105257658-105257678UCUUUCGGUGUACGUUGACA9414
54790_6_6287−chr4: 105257686-105257706CCGAAACUUUUAUAUAAGGA9415
54790_6_6289−chr4: 105257687-105257707UCCGAAACUUUUAUAUAAGG9416
54790_6_6293−chr4: 105257707-105257727CUUUACUCUACUAGGUGUCC9417
54790_6_6296−chr4: 105257710-105257730ACCCUUUACUCUACUAGGUG9418
54790_6_6300−chr4: 105257729-105257749UCGAAUUUUCAUUUAAUGGA9419
54790_6_6303−chr4: 105257730-105257750UUCGAAUUUUCAUUUAAUGG9420
54790_6_6306−chr4: 105257776-105257796UGAGUCCACAUCGAUUAUUG9421
54790_6_6310−chr4: 105257792-105257812AACUUAUAACAGUGACUGAG9422
54790_6_6314−chr4: 105257821-105257841CCGUAAACAGUUUAUUAGUA9423
54790_6_6318−chr4: 105257842-105257862CACUUGGUGGAAAAGGUGUC9424
54790_6_6328−chr4: 105257877-105257897AUAGAAAUGAAAUAGAUUGA9425
54790_6_6333−chr4: 105257901-105257921GGACCUUCUAGGGUGAUCAU9426
54790_6_6339−chr4: 105257919-105257939ACUGGACAAACCAUCAAAGG9427
54790_6_6343−chr4: 105257930-105257950GAAUGUAAUAAACUGGACAA9428
54790_6_6349−chr4: 105257982-105258002ACCUAUAUGAGAUCUGACCA9429
54790_6_6351−chr4: 105257986-105258006ACCAACCUAUAUGAGAUCUG9430
54790_6_6352−chr4: 105258002-105258022GAUCUCCUCCGGUCUAACCA9431
54790_6_6354−chr4: 105258006-105258026CGGUGAUCUCCUCCGGUCUA9432
54790_6_6355−chr4: 105258015-105258035UCGGUCCGACGGUGAUCUCC9433
54790_6_6357−chr4: 105258018-105258038UCGUCGGUCCGACGGUGAUC9434
54790_6_6363−chr4: 105258031-105258051AUAAUACUUUUCGUCGUCGG9435
54790_6_6371−chr4: 105258082-105258102AUUGAAAGGGGUGUCGAGAU9436
54790_6_6374−chr4: 105258110-105258130UCACUCUUCUCACUCGAGAC9437
54790_6_6383−chr4: 105258138-105258158ACAAGUUCCCUUUUUUUCUG9438
54790_6_6386−chr4: 105258151-105258171AUAUCCCUCUUAAACAAGUU9439
54790_6_6387−chr4: 105258152-105258172UAUAUCCCUCUUAAACAAGU9440
54790_6_6394−chr4: 105258167-105258187UUUUUCGAACGUCGUUAUAU9441
54790_6_6395−chr4: 105258168-105258188GUUUUUCGAACGUCGUUAUA9442
54790_6_6404−chr4: 105258198-105258218UCUUAGUCGAAAAAGUCUAG9443
54790_6_6411−chr4: 105258276-105258296AGUCGUUUUUACCGUCUUAU9444
54790_6_6416−chr4: 105258286-105258306AAAUGUCUACAGUCGUUUUU9445
54790_6_6424−chr4: 105258333-105258353AAGGUCGAUUAUUUACGUUU9446
54790_6_6428−chr4: 105258373-105258393UACCAUUGAUUGCCAACUAC9447
54790_6_6432−chr4: 105258382-105258402GAUAUAAUUUACCAUUGAUU9448
54790_6_6435−chr4: 105258392-105258412AAGAAUGUUUGAUAUAAUUU9449
54790_6_6451−chr4: 105258514-105258534CAUUACUGUGGAGGUAUCGU9450
54790_6_6452−chr4: 105258515-105258535UCAUUACUGUGGAGGUAUCG9451
54790_6_6472−chr4: 105258631-105258651UAUGAGACAGUUGAUACUUA9452
54790_6_6494−chr4: 105258769-105258789UGAAUGUUCUUUUUUAUAAG9453
54790_6_6508−chr4: 105258883-105258903CUCACGAUCCAGGAUCAAAG9454
54790_6_6510−chr4: 105258896-105258916AACUACCCGUAAACUCACGA9455
54790_6_6514−chr4: 105258911-105258931ACUUAAUAAGAUGGUAACUA9456
54790_6_6515−chr4: 105258912-105258932UACUUAAUAAGAUGGUAACU9457
54790_6_6536−chr4: 105259013-105259033CACGAAAAAGGUAAUACAAA9458
54790_6_6540−chr4: 105259014-105259034ACACGAAAAAGGUAAUACAA9459
54790_6_6545−chr4: 105259063-105259083UUGAUAUAUACAUAGGUAUU9460
54790_6_6551−chr4: 105259070-105259090AAAAUACUUGAUAUAUACAU9461
54790_6_6556−chr4: 105259127-105259147AGGGUUUAUCGACCUUGAUA9462
54790_6_6558−chr4: 105259136-105259156CGGAGUCGGAGGGUUUAUCG9463
54790_6_6564−chr4: 105259175-105259195GUCCAACUUGGACUUGAAGA9464
54790_6_6565−chr4: 105259176-105259196AGUCCAACUUGGACUUGAAG9465
54790_6_6570−chr4: 105259194-105259214CCCCAGAACGAUACAACGAG9466
54790_6_6578−chr4: 105259213-105259233UGCAAAGAAAAAAUGUCUAC9467
54790_6_6580−chr4: 105259214-105259234AUGCAAAGAAAAAAUGUCUA9468
54790_6_6581−chr4: 105259215-105259235AAUGCAAAGAAAAAAUGUCU9469
54790_6_6601−chr4: 105259334-105259354UGUUUUAUAAAUGAUAGGGG9470
54790_6_6612−chr4: 105259391-105259411UAUUAAAAUGUCAAAUGUUU9471
54790_6_6629−chr4: 105259492-105259512AGAUUGAGACAUAAUUCGAC9472
54790_6_6637−chr4: 105259551-105259571GGCUGUGCAGCUGAUAUUAU9473
54790_6_6641−chr4: 105259572-105259592UGCUAUGGAUAGCAUUAUAU9474
54790_7_20+chr4: 105259833-105259853GUGAACAAUAUGACAUAUCU9475
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54790_9_400+chr4: 105271572-105271592ACUUCUGUGCAGAAAGUGAC10204
54790_9_431+chr4: 105271812-105271832UUUAAUUAUCAAAGCAACAG10205
54790_9_439+chr4: 105271863-105271883UUUCAGAGUACCCACUUAUA10206
54790_9_456+chr4: 105271903-105271923AAUGAAGAAAAGAGAAAGUU10207
54790_9_459+chr4: 105271921-105271941UUAGGUUUGACAGAGUACAA10208
54790_9_464+chr4: 105271924-105271944GGUUUGACAGAGUACAAAGG10209
54790_9_486+chr4: 105272024-105272044UUUUUACUUCAGUUAUCUUA10210
54790_9_497+chr4: 105272050-105272070UUUCUUAAACAGAGAGAGUU10211
54790_9_500+chr4: 105272057-105272077AACAGAGAGAGUUAGGUGUC10212
54790_9_508+chr4: 105272102-105272122GUGUUCAGAAGUAUGAGAUG10213
54790_9_515+chr4: 105272129-105272149UGUGAUACUACCAAAAACAG10214
54790_9_522+chr4: 105272172-105272192CUUUUAGCCUGUUUUUGAAG10215
54790_9_541+chr4: 105272231-105272251AGCAAGAGAGUGCUUCAUUU10216
54790_9_543+chr4: 105272232-105272252GCAAGAGAGUGCUUCAUUUU10217
54790_9_544+chr4: 105272233-105272253CAAGAGAGUGCUUCAUUUUG10218
54790_9_546+chr4: 105272234-105272254AAGAGAGUGCUUCAUUUUGG10219
54790_9_560+chr4: 105272279-105272299AGAAACAUAUGUGAAGAACA10220
54790_9_561+chr4: 105272280-105272300GAAACAUAUGUGAAGAACAA10221
54790_9_566+chr4: 105272319-105272339UUCCUGAUAGACUCAGAGAA10222
54790_9_567+chr4: 105272320-105272340UCCUGAUAGACUCAGAGAAA10223
54790_9_570+chr4: 105272323-105272343UGAUAGACUCAGAGAAAGGG10224
54790_9_571+chr4: 105272324-105272344GAUAGACUCAGAGAAAGGGU10225
54790_9_573+chr4: 105272327-105272347AGACUCAGAGAAAGGGUGGG10226
54790_9_574+chr4: 105272328-105272348GACUCAGAGAAAGGGUGGGU10227
54790_9_580+chr4: 105272387-105272407UUGCUAUUUUCAUUAAUAAC10228
54790_9_584+chr4: 105272391-105272411UAUUUUCAUUAAUAACAGGU10229
54790_9_585+chr4: 105272395-105272415UUCAUUAAUAACAGGUAGGA10230
54790_9_590+chr4: 105272403-105272423UAACAGGUAGGAUGGUUUUA10231
54790_9_595+chr4: 105272426-105272446UAAUAUAUAUGUCACUGAUC10232
54790_9_596+chr4: 105272436-105272456GUCACUGAUCUGGAUCAACU10233
54790_9_601+chr4: 105272465-105272485ACACAAAUCUGAAUACUGAG10234
54790_9_606+chr4: 105272500-105272520ACACACACACACGUUUUCUU10235
54790_9_608+chr4: 105272501-105272521CACACACACACGUUUUCUUU10236
54790_9_610+chr4: 105272515-105272535UUCUUUGGGACCUGUAGUUG10237
54790_9_631−chr4: 105269865-105269885CACUCCGGAGGUGUCGGUAC10238
54790_9_637−chr4: 105269882-105269902ACGGAAGUCGAUACUAACAC10239
54790_9_647−chr4: 105269965-105269985CUAGACUACUAAAAUAUUUC10240
54790_9_650−chr4: 105269966-105269986UCUAGACUACUAAAAUAUUU10241
54790_9_651−chr4: 105269967-105269987CUCUAGACUACUAAAAUAUU10242
54790_9_660−chr4: 105270004-105270024UAGAAAGGGUACGACAAGAG10243
54790_9_663−chr4: 105270030-105270050CCCUCCAUUAACUUAGUACC10244
54790_9_664−chr4: 105270031-105270051ACCCUCCAUUAACUUAGUAC10245
54790_9_665−chr4: 105270032-105270052CACCCUCCAUUAACUUAGUA10246
54790_9_668−chr4: 105270033-105270053UCACCCUCCAUUAACUUAGU10247
54790_9_674−chr4: 105270047-105270067AAACCCUUCCUGGGUCACCC10248
54790_9_676−chr4: 105270050-105270070ACAAAACCCUUCCUGGGUCA10249
54790_9_677−chr4: 105270051-105270071CACAAAACCCUUCCUGGGUC10250
54790_9_681−chr4: 105270060-105270080UUAAGGGUACACAAAACCCU10251
54790_9_683−chr4: 105270064-105270084GGUUUUAAGGGUACACAAAA10252
54790_9_685−chr4: 105270065-105270085GGGUUUUAAGGGUACACAAA10253
54790_9_691−chr4: 105270125-105270145GAGAUGCUGCACUAUACCAG10254
54790_9_692−chr4: 105270130-105270150AACAUGAGAUGCUGCACUAU10255
54790_9_706−chr4: 105270245-105270265AAAGCAGGUCACUUUGCAAC10256
54790_9_709−chr4: 105270260-105270280AGUGCUAGUUAUGCCAAAGC10257
54790_9_714−chr4: 105270309-105270329UGCUUGUCAACACAAUUGAC10258
54790_9_723−chr4: 105270350-105270370ACUGGUUUAGAUUAACACCA10259
54790_9_725−chr4: 105270368-105270388AACUGGCAAUGCAUAGUCAC10260
54790_9_730−chr4: 105270385-105270405UCCUGGAAGUUAACUGUAAC10261
54790_9_735−chr4: 105270402-105270422ACUGAAUUUUGAGAUUUUCC10262
54790_9_740−chr4: 105270426-105270446AUUACAAUCUACCAGGUAAC10263
54790_9_744−chr4: 105270433-105270453UUAACUGAUUACAAUCUACC10264
54790_9_750−chr4: 105270464-105270484UAAGGUGAAUGGCUUGUAUU10265
54790_9_752−chr4: 105270475-105270495UUCUCUCUCUGUAAGGUGAA10266
54790_9_754−chr4: 105270482-105270502AAUAUGCUUCUCUCUCUGUA10267
54790_9_759−chr4: 105270507-105270527UUUAUGCUUCUCUCUCUGUA10268
54790_9_770−chr4: 105270568-105270588CACUGUGAAUCUUUUACAAU10269
54790_9_775−chr4: 105270599-105270619ACCCACUGUAAUAUGUAGUC10270
54790_9_786−chr4: 105270710-105270730UUAUACCCUGAACCCUUUGU10271
54790_9_796−chr4: 105270753-105270773UUGUUCUUUAUCUCUACUCU10272
54790_9_797−chr4: 105270754-105270774UUUGUUCUUUAUCUCUACUC10273
54790_9_811−chr4: 105270809-105270829AUCCAUGUUGAUAAUUCAUU10274
54790_9_848−chr4: 105271073-105271093UUACACUGUCUUUAGGAUAC10275
54790_9_861−chr4: 105271137-105271157CUUACCAAAAAUGUAAAAGU10276
54790_9_866−chr4: 105271154-105271174AUACCGGUCAUUUGAUUCUU10277
54790_9_869−chr4: 105271172-105271192GGAGUGUCGAACACAAACAU10278
54790_9_871−chr4: 105271203-105271223UCAAUCCUUUGGUCUUGGAU10279
54790_9_879−chr4: 105271219-105271239GUUCUUCUGGAUGUCUUCAA10280
54790_9_885−chr4: 105271232-105271252AGGCCUUGUGUUUGUUCUUC10281
54790_9_891−chr4: 105271252-105271272UAGAUGUUGGGGUGGUUGGU10282
54790_9_892−chr4: 105271256-105271276AUUUUAGAUGUUGGGGUGGU10283
54790_9_894−chr4: 105271260-105271280GAUGAUUUUAGAUGUUGGGG10284
54790_9_895−chr4: 105271263-105271283AGUGAUGAUUUUAGAUGUUG10285
54790_9_896−chr4: 105271264-105271284UAGUGAUGAUUUUAGAUGUU10286
54790_9_898−chr4: 105271265-105271285UUAGUGAUGAUUUUAGAUGU10287
54790_9_901−chr4: 105271302-105271322AUAGCCUCCUAAUAAUGAGC10288
54790_9_913−chr4: 105271377-105271397GAAUGAAACAUGGUUAUAUU10289
54790_9_916−chr4: 105271387-105271407CACCUUCCUGGAAUGAAACA10290
54790_9_919−chr4: 105271399-105271419CUUACUCUCUGUCACCUUCC10291
54790_9_928−chr4: 105271458-105271478CAGAACCCAUGCUCUAUCAG10292
54790_9_959−chr4: 105271608-105271628GAAAUAACUUCAACAUGAGA10293
54790_9_964−chr4: 105271641-105271661UGAGAGAAAUGUGAUCACAA10294
54790_9_981−chr4: 105271711-105271731UAUUUAGUGUUUUUGAUCAA10295
54790_9_994−chr4: 105271756-105271776CUUUGGUAAAAGAUUAUUUG10296
54790_9_998−chr4: 105271773-105271793UACUACAAUUACACUAGCUU10297
54790_9_1008−chr4: 105271812-105271832CUGUUGCUUUGAUAAUUAAA10298
54790_9_1009−chr4: 105271845-105271865AAAGGGUAAGGGGUGGAGGG10299
(TI-7) (6900)
54790_9_1012−chr4: 105271848-105271868UGAAAAGGGUAAGGGGUGGA10300
54790_9_1015−chr4: 105271849-105271869CUGAAAAGGGUAAGGGGUGG10301
(TI-8) (7600)
54790_9_1017−chr4: 105271852-105271872ACUCUGAAAAGGGUAAGGGG10302
54790_9_1020−chr4: 105271855-105271875GGUACUCUGAAAAGGGUAAG10303
54790_9_1021−chr4: 105271856-105271876GGGUACUCUGAAAAGGGUAA10304
54790_9_1023−chr4: 105271857-105271877UGGGUACUCUGAAAAGGGUA10305
54790_9_1025−chr4: 105271862-105271882AUAAGUGGGUACUCUGAAAA10306
54790_9_1026−chr4: 105271863-105271883UAUAAGUGGGUACUCUGAAA10307
54790_9_1032−chr4: 105271876-105271896UGAAAUAUGACCAUAUAAGU10308
54790_9_1033−chr4: 105271877-105271897CUGAAAUAUGACCAUAUAAG10309
54790_9_1053−chr4: 105271989-105272009GGUAAAGAUUUGGCUGAUAC10310
54790_9_1054−chr4: 105271999-105272019AAAAUGAAAAGGUAAAGAUU10311
54790_9_1055−chr4: 105272010-105272030UAAAAAUAUAAAAAAUGAAA10312
54790_9_1078−chr4: 105272142-105272162GAAAUGACUUCCUCUGUUUU10313
54790_9_1085−chr4: 105272182-105272202UGUGAAGCCUCUUCAAAAAC10314
54790_9_1100−chr4: 105272273-105272293UCACAUAUGUUUCUGUCUAU10315
54790_9_1102−chr4: 105272274-105272294UUCACAUAUGUUUCUGUCUA10316
54790_9_1106−chr4: 105272309-105272329CUAUCAGGAACAGUUAGCUG10317
54790_9_1109−chr4: 105272324-105272344ACCCUUUCUCUGAGUCUAUC10318
54790_9_1116−chr4: 105272375-105272395AAUAGCAACAAAAUGGUACA10319
54790_9_1117−chr4: 105272376-105272396AAAUAGCAACAAAAUGGUAC10320
54790_9_1122−chr4: 105272382-105272402UAAUGAAAAUAGCAACAAAA10321
54790_9_1130−chr4: 105272462-105272482AGUAUUCAGAUUUGUGUUGG10322
54790_9_1131−chr4: 105272465-105272485CUCAGUAUUCAGAUUUGUGU10323
54790_9_1136−chr4: 105272528-105272548GACAUUACAGCCUCAACUAC10324
54790_10_4+chr4: 105272938-105272958UUGUAGAUAAAUGUGUUGUG10325
54790_10_9+chr4: 105272964-105272984AUUAAAAAUGAAAAUUAUUU10326
54790_10_20+chr4: 105272993-105273013CCCCAUCAACUUGUAAGUUC10327
54790_10_21+chr4: 105272994-105273014CCCAUCAACUUGUAAGUUCU10328
54790_10_22+chr4: 105272995-105273015CCAUCAACUUGUAAGUUCUG10329
54790_10_25+chr4: 105273007-105273027AAGUUCUGGGGUACACAUGC10330
54790_10_27+chr4: 105273016-105273036GGUACACAUGCAGGAUGUGC10331
54790_10_28+chr4: 105273029-105273049GAUGUGCAGGUUUGUUAUAC10332
54790_10_31+chr4: 105273045-105273065AUACAGGUAAACAUGUGCCA10333
54790_10_35+chr4: 105273078-105273098CACAGAUCAACCCAUUACCU10334
54790_10_38+chr4: 105273119-105273139CCUGAUGCACCCCUACCAAU10335
54790_10_46+chr4: 105273196-105273216AAAAUGAACAUUGUUAAUUU10336
54790_10_49+chr4: 105273215-105273235UUGGAAAGUUAUAUCAAUCA10337
54790_10_58+chr4: 105273254-105273274GAGUCUUCUCUAAAGUAGCA10338
54790_10_59+chr4: 105273255-105273275AGUCUUCUCUAAAGUAGCAA10339
54790_10_60+chr4: 105273260-105273280UCUCUAAAGUAGCAAGGGCC10340
54790_10_63+chr4: 105273278-105273298CCAGGCUUUGUUCUCAGAGA10341
54790_10_70+chr4: 105273305-105273325GAGAUAUUGCACCAUCAACA10342
54790_10_73+chr4: 105273314-105273334CACCAUCAACAUGGAAAACA10343
54790_10_76+chr4: 105273324-105273344AUGGAAAACAUGGAAAAGUC10344
54790_10_81+chr4: 105273362-105273382AAACAGCAACUUUUUUUAAC10345
54790_10_89+chr4: 105273394-105273414CGAUGAAAUUCAUUGUAAUU10346
54790_10_90+chr4: 105273401-105273421AUUCAUUGUAAUUUGGCAGU10347
54790_10_96+chr4: 105273416-105273436GCAGUAGGCCAAAUUAGUAG10348
54790_10_101+chr4: 105273430-105273450UAGUAGAGGAGCUAAUAGUU10349
54790_10_107+chr4: 105273458-105273478AACACAGUAAACCAGAACUG10350
54790_10_109+chr4: 105273482-105273502AACAAGACCUUGAAUUUUGU10351
54790_10_118+chr4: 105273532-105273552GCAAAUGAGCUCUUCCAAAA10352
54790_10_120+chr4: 105273533-105273553CAAAUGAGCUCUUCCAAAAU10353
54790_10_125+chr4: 105273551-105273571AUGGGAAAAAGAAAAUACAU10354
54790_10_128+chr4: 105273565-105273585AUACAUUGGUGACAAAACAC10355
54790_10_140+chr4: 105273634-105273654UAAACUUAACCUACUGUUUU10356
54790_10_162+chr4: 105273698-105273718AAUAUGAUUGAGAGAGAGAG10357
54790_10_163+chr4: 105273699-105273719AUAUGAUUGAGAGAGAGAGA10358
54790_10_165+chr4: 105273700-105273720UAUGAUUGAGAGAGAGAGAG10359
54790_10_175+chr4: 105273739-105273759CCUUAGACAUGUUGAGUCUG10360
54790_10_179+chr4: 105273745-105273765ACAUGUUGAGUCUGUGGUUU10361
54790_10_182+chr4: 105273748-105273768UGUUGAGUCUGUGGUUUAGG10362
54790_10_184+chr4: 105273749-105273769GUUGAGUCUGUGGUUUAGGA10363
54790_10_185+chr4: 105273750-105273770UUGAGUCUGUGGUUUAGGAG10364
54790_10_210+chr4: 105273911-105273931AAGAAAAAAAAUCCAAAAUU10365
54790_10_212+chr4: 105273912-105273932AGAAAAAAAAUCCAAAAUUU10366
54790_10_213+chr4: 105273916-105273936AAAAAAUCCAAAAUUUGGGA10367
54790_10_214+chr4: 105273922-105273942UCCAAAAUUUGGGAUGGUAU10368
54790_10_215+chr4: 105273927-105273947AAUUUGGGAUGGUAUUGGCC10369
54790_10_231+chr4: 105274022-105274042UGAUUCAUUUCCAAGCUCAG10370
54790_10_241+chr4: 105274080-105274100CUUGAUAAGUGUUUAUUGAC10371
54790_10_248+chr4: 105274115-105274135UAAGUAAAUACUGUUCACUU10372
54790_10_255+chr4: 105274168-105274188UGUCUCUGCUCCCUUUUAAC10373
54790_10_257+chr4: 105274178-105274198CCCUUUUAACUGGCUUCUGC10374
54790_10_273+chr4: 105274258-105274278UCAUAUGACUUUUUAAAGUG10375
54790_10_293+chr4: 105274350-105274370AACUGUGUUAACUUCCUUUC10376
54790_10_325+chr4: 105274496-105274516AGCAAAUUCCAUUGCAUGCC10377
54790_10_334+chr4: 105274541-105274561AAACAUUUUCCUUCCCAUUU10378
54790_10_340+chr4: 105274558-105274578UUUAGGAAUUUACUUACCAG10379
54790_10_342+chr4: 105274559-105274579UUAGGAAUUUACUUACCAGU10380
54790_10_344+chr4: 105274560-105274580UAGGAAUUUACUUACCAGUG10381
54790_10_346+chr4: 105274561-105274581AGGAAUUUACUUACCAGUGG10382
54790_10_354+chr4: 105274571-105274591UUACCAGUGGGGGUGAAGAG10383
54790_10_355+chr4: 105274572-105274592UACCAGUGGGGGUGAAGAGA10384
54790_10_368+chr4: 105274660-105274680UACAAAAGCACUAGAAGAUG10385
54790_10_370+chr4: 105274669-105274689ACUAGAAGAUGAGGUCAAAG10386
54790_10_374+chr4: 105274679-105274699GAGGUCAAAGCGGUCCCUUG10387
54790_10_376+chr4: 105274683-105274703UCAAAGCGGUCCCUUGAGGA10388
54790_10_378+chr4: 105274684-105274704CAAAGCGGUCCCUUGAGGAA10389
54790_10_382+chr4: 105274699-105274719AGGAAGGGAUGACUACACCA10390
54790_10_384+chr4: 105274703-105274723AGGGAUGACUACACCAAGGA10391
54790_10_386+chr4: 105274708-105274728UGACUACACCAAGGAAGGAU10392
54790_10_388+chr4: 105274709-105274729GACUACACCAAGGAAGGAUA10393
54790_10_393+chr4: 105274716-105274736CCAAGGAAGGAUAGGGAGAG10394
54790_10_396+chr4: 105274717-105274737CAAGGAAGGAUAGGGAGAGA10395
54790_10_398+chr4: 105274720-105274740GGAAGGAUAGGGAGAGAGGG10396
54790_10_401+chr4: 105274726-105274746AUAGGGAGAGAGGGAGGAAA10397
54790_10_404+chr4: 105274727-105274747UAGGGAGAGAGGGAGGAAAA10398
54790_10_405+chr4: 105274730-105274750GGAGAGAGGGAGGAAAAGGG10399
54790_10_407+chr4: 105274745-105274765AAGGGAGGCACUUCAAGCAG10400
54790_10_415+chr4: 105274784-105274804AAAGAACAUUUUGCUCUCAA10401
54790_10_416+chr4: 105274789-105274809ACAUUUUGCUCUCAAUGGAA10402
54790_10_418+chr4: 105274795-105274815UGCUCUCAAUGGAAUGGCUU10403
54790_10_442+chr4: 105274863-105274883CCUUAGACAAAAAAUUGUGC10404
54790_10_447+chr4: 105274907-105274927UUGCUCUUAUCUUUGCUUAA10405
54790_10_448+chr4: 105274908-105274928UGCUCUUAUCUUUGCUUAAU10406
54790_10_457+chr4: 105274927-105274947UGGGUGUCGUAUAUCACUAG10407
54790_10_477−chr4: 105272995-105273015GUCUUGAAUGUUGUUGAUGG10408
54790_10_478−chr4: 105272996-105273016GGUCUUGAAUGUUGUUGAUG10409
54790_10_479−chr4: 105272997-105273017GGGUCUUGAAUGUUGUUGAU10410
54790_10_482−chr4: 105272998-105273018GGGGUCUUGAAUGUUGUUGA10411
54790_10_489−chr4: 105273065-105273085UAGACACGUCGUUUAGUGGU10412
54790_10_491−chr4: 105273091-105273111CCCGAAUUAUGGAUCCAUUA10413
54790_10_492−chr4: 105273092-105273112ACCCGAAUUAUGGAUCCAUU10414
54790_10_494−chr4: 105273098-105273118UCUACGACCCGAAUUAUGGA10415
54790_10_495−chr4: 105273111-105273131CCCACGUAGUCCUUCUACGA10416
54790_10_496−chr4: 105273112-105273132CCCCACGUAGUCCUUCUACG10417
54790_10_499−chr4: 105273122-105273142GGAUAACCAUCCCCACGUAG10418
54790_10_502−chr4: 105273131-105273151UGUGACCGCGGAUAACCAUC10419
54790_10_503−chr4: 105273132-105273152GUGUGACCGCGGAUAACCAU10420
54790_10_505−chr4: 105273133-105273153UGUGUGACCGCGGAUAACCA10421
54790_10_507−chr4: 105273137-105273157GUUGUGUGUGACCGCGGAUA10422
54790_10_508−chr4: 105273147-105273167CCUCACCCCUGUUGUGUGUG10423
54790_10_509−chr4: 105273161-105273181CCUGUGUACCACCCCCUCAC10424
54790_10_511−chr4: 105273162-105273182ACCUGUGUACCACCCCCUCA10425
54790_10_513−chr4: 105273163-105273183UACCUGUGUACCACCCCCUC10426
54790_10_515−chr4: 105273168-105273188UCGUGUACCUGUGUACCACC10427
54790_10_518−chr4: 105273169-105273189CUCGUGUACCUGUGUACCAC10428
54790_10_520−chr4: 105273170-105273190UCUCGUGUACCUGUGUACCA10429
54790_10_521−chr4: 105273171-105273191UUCUCGUGUACCUGUGUACC10430
54790_10_526−chr4: 105273174-105273194AUAUUCUCGUGUACCUGUGU10431
54790_10_529−chr4: 105273182-105273202CAUUUUACAUAUUCUCGUGU10432
54790_10_541−chr4: 105273254-105273274UGCUACUUUAGAGAAGACUC10433
54790_10_546−chr4: 105273281-105273301CCAUCUCUGAGAACAAAGCC10434
54790_10_557−chr4: 105273319-105273339UUCCAUGUUUUCCAUGUUGA10435
54790_10_572−chr4: 105273427-105273447UAUUAGCUCCUCUACUAAUU10436
54790_10_581−chr4: 105273472-105273492AGGUCUUGUUACCUCAGUUC10437
54790_10_584−chr4: 105273492-105273512CUACUAACCAACAAAAUUCA10438
54790_10_601−chr4: 105273549-105273569GUAUUUUCUUUUUCCCAUUU10439
54790_10_623−chr4: 105273620-105273640ACAAAUCCAAAUUUUGAAAC10440
54790_10_624−chr4: 105273621-105273641AACAAAUCCAAAUUUUGAAA10441
54790_10_625−chr4: 105273622-105273642UAACAAAUCCAAAUUUUGAA10442
54790_10_628−chr4: 105273635-105273655UAAAACAGUAGGUUAACAAA10443
54790_10_632−chr4: 105273646-105273666UUUUAGAAACCUAAAACAGU10444
54790_10_644−chr4: 105273742-105273762CCACAGACUCAACAUGUCUA10445
54790_10_655−chr4: 105273808-105273828CAGCUGUAAUCUAUUUUGAU10446
54790_10_657−chr4: 105273809-105273829ACAGCUGUAAUCUAUUUUGA10447
54790_10_665−chr4: 105273879-105273899AGACAUAAAGCAGGAGGCUA10448
54790_10_670−chr4: 105273885-105273905AACUGCAGACAUAAAGCAGG10449
54790_10_674−chr4: 105273888-105273908ACAAACUGCAGACAUAAAGC10450
54790_10_686−chr4: 105273926-105273946GCCAAUACCAUCCCAAAUUU10451
54790_10_694−chr4: 105273948-105273968GUUUGCUUUUGUUAAUGGCC10452
54790_10_695−chr4: 105273953-105273973AACUGGUUUGCUUUUGUUAA10453
54790_10_699−chr4: 105273970-105273990AUGGCUAGUUUUAAGCAAAC10454
54790_10_703−chr4: 105273989-105274009ACUUCAUGAAGCAGCAAAGA10455
54790_10_715−chr4: 105274035-105274055UAACUUAGUUCCUCUGAGCU10456
54790_10_732−chr4: 105274168-105274188GUUAAAAGGGAGCAGAGACA10457
54790_10_737−chr4: 105274181-105274201CCUGCAGAAGCCAGUUAAAA10458
54790_10_738−chr4: 105274182-105274202ACCUGCAGAAGCCAGUUAAA10459
54790_10_744−chr4: 105274211-105274231UGGCAGUUCUGAGAACAGAA10460
54790_10_746−chr4: 105274212-105274232AUGGCAGUUCUGAGAACAGA10461
54790_10_753−chr4: 105274231-105274251ACAAAUAGAUGAAACUGCAA10462
54790_10_783−chr4: 105274367-105274387UAUAAGCAGGCUUUCCAGAA10463
54790_10_786−chr4: 105274380-105274400ACAAGUGCUACUUUAUAAGC10464
54790_10_798−chr4: 105274462-105274482AGAUUUAUUAUGUAAGAUUC10465
54790_10_800−chr4: 105274463-105274483AAGAUUUAUUAUGUAAGAUU10466
54790_10_808−chr4: 105274507-105274527GAAGUAACGGACCGUACGUU10467
54790_10_816−chr4: 105274517-105274537AAUGAAUGAAGAAGUAACGG10468
54790_10_820−chr4: 105274553-105274573UUCAUUUAAGGAUUUACCCU10469
54790_10_824−chr4: 105274557-105274577ACCAUUCAUUUAAGGAUUUA10470
54790_10_825−chr4: 105274558-105274578GACCAUUCAUUUAAGGAUUU10471
54790_10_833−chr4: 105274577-105274597UCGGGAGAGAAGUGGGGGUG10472
54790_10_844−chr4: 105274696-105274716ACAUCAGUAGGGAAGGAGUU10473
54790_10_846−chr4: 105274697-105274717CACAUCAGUAGGGAAGGAGU10474
54790_10_849−chr4: 105274719-105274739GGAGAGAGGGAUAGGAAGGA10475
54790_10_863−chr4: 105274785-105274805AUUGAGAGCAAAAUGUUGAA10476
54790_10_877−chr4: 105274866-105274886CCAGCACAAUUUUUUGUCUA10477
54790_10_880−chr4: 105274902-105274922CAAAGAUAAGAGCAAAGUCA10478
54790_10_881−chr4: 105274903-105274923GCAAAGAUAAGAGCAAAGUC10479
54790_10_886−chr4: 105274962-105274982UAGUGAGGAUACUUAAAUGU10480
54790_10_891−chr4: 105274977-105274997UUAUUUUAUGAAGGCUAGUG10481
54790_10_897−chr4: 105274986-105275006UGUUGAUGAUUAUUUUAUGA10482
CR007677chr4: 105271204-105271223AGUUAGGAAACCAGAACCUA10515
TABLE 2 — Exemplary gRNA Targeting Domains for the TET2 intron between exon 9 and exon 10 (mm0, mm1, mm2 and mm3 refer to the predicted number of target sequences within the genome with 0, 1 2, or 3 mismatch bases, respectively). Throughout this application, gRNAs comprising the targeting domains listed in this Table 2 may be referred to as “gX” where “X” indicates the second number of the “ID” shown in this table (thus, for example, a gRNA comprising the targeting domain of HTET2_1 may be referred to herein as “g1.”
gRNA Targeting DomainSEQ ID
IDStrandSequence (20 nt)NO:mm0mm1mm2mm3
HTET2_1+UGGAUCGGUCUUGUAAUUGG101481001
(g1)
HTET2_2+CUGUGAGGCACAUUAGCCGU101841001
HTET2_3−CUUUGUCGGCAAGUCUUGAC104831001
HTET2_4+GGCACAUUAGCCGUAGGUUC101851002
(g4)
HTET2_5+GUCUCUGACGUGGAUGAGUU104841002
HTET2_6+CUAGCACUCUCAUGAUAGGU101371003
HTET2_7+GCCAGUUACAGUUAACUUCC101401003
HTET2_8+AGAGCACCAGAGUGCCGUCU104851004
HTET2_9+CACAUUGGUAAGUUGGGCUG101041004
HTET2_10+GUCACUGAUCUGGAUCAACU102331004
(g10)
HTET2_11+UCUCUGACGUGGAUGAGUUU104861004
HTET2_12+CAGUCAAGACUUGCCGACAA104871004
HTET2_13−GUGAGAGUGCAUACCUGGUA104881004
HTET2_14−CUCUAGUGAGAGUGCAUACC104891004
HTET2_15−AUUUGAGCUGUUCUCCAGGG104901004
HTET2_16+CAGAGCACCAGAGUGCCGUC104911005
HTET2_17+AGCACCUGCUCAUUAUUAGG101881005
(g17)
HTET2_18+CGCAAGCCAGGCUAAACAGU104921005
HTET2_19+CAUGUUGAGGAGCAGAACAC101311006
HTET2_20+GGUUUGACAGAGUACAAAGG102091006
(g20)
HTET2_21+AACAGAGAGAGUUAGGUGUC102121006
(g21)
HTET2_22−CUAUCAGGAACAGUUAGCUG103171006
(g22)
HTET2_23−ACCCUUUCUCUGAGUCUAUC103181006
(g23)
HTET2_24+AUGUUGUCUGCAGGUUUCAC101341007
HTET2_25+CUCAGCACCUGCUCAUUAUU101871007
(g25)
HTET2_26−AGUGCUAGUUAUGCCAAAGC102571012
HTET2_27+AGAGUGCCGUCUGGGUCUGA105161008
HTET2_28+AAGGAAGGCCGUCCAUUCUC104931013
HTET2_29+AUCAGCAGCAUCUCAUGUUG101301014
HTET2_30+UUCUUUGGGACCUGUAGUUG102371009
HTET2_31−AACUGGCAAUGCAUAGUCAC102601009
HTET2_32−AGUGAGAGUGCAUACCUGGU1049410010
HTET2_33+AGGAAGGCCGUCCAUUCUCA1049510011
HTET2_34+UGAUAGACUCAGAGAAAGGG1022410011
(g34)
HTET2_35−UUCAGACCCAGACGGCACUC1049610011
HTET2_36−ACGUGAAGCUGCUCAUCCUC104971016
HTET2_37+GGAAGGCCGUCCAUUCUCAG104981017
HTET2_38+AUGGCAGCACAUUGGUAAGU101021017
HTET2_39−GCAUGUUGUGCAAGUCUCUG104991017
HTET2_40+GACUUGCACAACAUGCAGAA105001018
HTET2_41+GUUUGGGAGUGUGGAAGCUC105011018
HTET2_42−CAGAACCCAUGCUCUAUCAG1029210013
(g42)
HTET2_43−GACAUUACAGCCUCAACUAC103241018
HTET2_44+CAUGCAGAAUGGCAGCACAU105021019
HTET2_45+GGUCUUGUAAUUGGAGGCAG1014910112
(g45)
HTET2_46+CGUGGAUGAGUUUGGGAGUG105031107
HTET2_47+UGUUGCAAAGUGACCUGCUU1013510113
HTET2_48+UUAGGGACUGCAGGCCACAU101771028
(g48)
HTET2_49−CAUGUUGUGCAAGUCUCUGU1050410114
HTET2_50+UGGCAGCACAUUGGUAAGUU101031035
HTET2_51+UGGGAGUGUGGAAGCUCAGG1050510211
HTET2_52+UGCCGUCUGGGUCUGAAGGA1050611013
HTET2_53−AAAGCAGGUCACUUUGCAAC1025610024
HTET2_54+GUAAUUGGAGGCAGUGGUGA1015110120
(g54)
HTET2_55+GAUAGACUCAGAGAAAGGGU1022511015
(g55)
HTET2_56−GGCCUUCCUUCAGACCCAGA1050710310
HTET2_57−GAGAUGCUGCUGAUAUGGUC1050810120
HTET2_58−CCUCACAGCUUGUGUUUGUA1050910215
(g58)
HTET2_59−CACCUUCCUGGAAUGAAACA1029010216
(g59)
HTET2_60−AGGCCUUGUGUUUGUUCUUC1028110029
(g60)
HTET2_61−CUUACUCUCUGUCACCUUCC1029110220
HTET2_62+GACUCAGAGAAAGGGUGGGU1022710223
HTET2_63+CCAUACAAACACAAGCUGUG1018311427
HTET2_64+UAAUUGGAGGCAGUGGUGAG1015210343
HTET2_65+ACUUCUGUGCAGAAAGUGAC1020410629
HTET2_66+UGUAAUUGGAGGCAGUGGUG10150101354
HTET2_67−AUCUUUCCCAUGCUGUUCUC105102111760
HTET2_68+AGACUCAGAGAAAGGGUGGG1022621119146
HTET2_69+UUACUCUCCUGAGAACAGCA10119213228616
HTET2_70−UUUGGGAAGGACCCAGUGGG105112111531725
HTET2_71+UACUCUCCUGAGAACAGCAU10120292582845
HTET2_72+AGGCAAGAGAACAUGUGCAG10118294219801176
HTET2_73+GUCACAUCUUACAUGGCGGC10115554437181851
HTET2_74+GCAGGCAAGAGAACAUGUGC101163445510211158
HTET2_75+CAGGCAAGAGAACAUGUGCA101173446411061320
HTET2_76−UGCCUUCAGCUAUGAUUGUG10512613921573694
HTET2_77+GGCCUCACAAUCAUAGCUGA10111821429835040
HTET2_78−GUGAGGCCUCCACAGCCAUG1051361308064065844
HTET2_79+ACAGUUCCACAUGGCUGUGG10110105456957146456
HTET2_80−GGGAGGUAAUUGAAUCAUGG105142987546280298107
HTET2_81+CUCACAGUUCCACAUGGCUG101093142616274915859
(SEQ ID NO: 122)
atggataaaa agtacagcat cgggctggac atcggtacaa actcagtggg gtgggccgtg60
attacggacg agtacaaggt accctccaaa aaatttaaag tgctgggtaa cacggacaga120
cactctataa agaaaaatct tattggagcc ttgctgttcg actcaggcga gacagccgaa180
gccacaaggt tgaagcggac cgccaggagg cggtatacca ggagaaagaa ccgcatatgc240
tacctgcaag aaatcttcag taacgagatg gcaaaggttg acgatagctt tttccatcgc300
ctggaagaat cctttcttgt tgaggaagac aagaagcacg aacggcaccc catctttggc360
aatattgtcg acgaagtggc atatcacgaa aagtacccga ctatctacca cctcaggaag420
aagctggtgg actctaccga taaggcggac ctcagactta tttatttggc actcgcccac480
atgattaaat ttagaggaca tttcttgatc gagggcgacc tgaacccgga caacagtgac540
gtcgataagc tgttcatcca acttgtgcag acctacaatc aactgttcga agaaaaccct600
ataaatgctt caggagtcga cgctaaagca atcctgtccg cgcgcctctc aaaatctaga660
agacttgaga atctgattgc tcagttgccc ggggaaaaga aaaatggatt gtttggcaac720
ctgatcgccc tcagtctcgg actgacccca aatttcaaaa gtaacttcga cctggccgaa780
gacgctaagc tccagctgtc caaggacaca tacgatgacg acctcgacaa tctgctggcc840
cagattgggg atcagtacgc cgatctcttt ttggcagcaa agaacctgtc cgacgccatc900
ctgttgagcg atatcttgag agtgaacacc gaaattacta aagcacccct tagcgcatct960
atgatcaagc ggtacgacga gcatcatcag gatctgaccc tgctgaaggc tcttgtgagg1020
caacagctcc ccgaaaaata caaggaaatc ttctttgacc agagcaaaaa cggctacgct1080
ggctatatag atggtggggc cagtcaggag gaattctata aattcatcaa gcccattctc1140
gagaaaatgg acggcacaga ggagttgctg gtcaaactta acagggagga cctgctgcgg1200
aagcagcgga cctttgacaa cgggtctatc ccccaccaga ttcatctggg cgaactgcac1260
gcaatcctga ggaggcagga ggatttttat ccttttctta aagataaccg cgagaaaata1320
gaaaagattc ttacattcag gatcccgtac tacgtgggac ctctcgcccg gggcaattca1380
cggtttgcct ggatgacaag gaagtcagag gagactatta caccttggaa cttcgaagaa1440
gtggtggaca agggtgcatc tgcccagtct ttcatcgagc ggatgacaaa ttttgacaag1500
aacctcccta atgagaaggt gctgcccaaa cattctctgc tctacgagta ctttaccgtc1560
tacaatgaac tgactaaagt caagtacgtc accgagggaa tgaggaagcc ggcattcctt1620
agtggagaac agaagaaggc gattgtagac ctgttgttca agaccaacag gaaggtgact1680
gtgaagcaac ttaaagaaga ctactttaag aagatcgaat gttttgacag tgtggaaatt1740
tcaggggttg aagaccgctt caatgcgtca ttggggactt accatgatct tctcaagatc1800
ataaaggaca aagacttcct ggacaacgaa gaaaatgagg atattctcga agacatcgtc1860
ctcaccctga ccctgttcga agacagggaa atgatagaag agcgcttgaa aacctatgcc1920
cacctcttcg acgataaagt tatgaagcag ctgaagcgca ggagatacac aggatgggga1980
agattgtcaa ggaagctgat caatggaatt agggataaac agagtggcaa gaccatactg2040
gatttcctca aatctgatgg cttcgccaat aggaacttca tgcaactgat tcacgatgac2100
tctcttacct tcaaggagga cattcaaaag gctcaggtga gcgggcaggg agactccctt2160
catgaacaca tcgcgaattt ggcaggttcc cccgctatta aaaagggcat ccttcaaact2220
gtcaaggtgg tggatgaatt ggtcaaggta atgggcagac ataagccaga aaatattgtg2280
atcgagatgg cccgcgaaaa ccagaccaca cagaagggcc agaaaaatag tagagagcgg2340
atgaagagga tcgaggaggg catcaaagag ctgggatctc agattctcaa agaacacccc2400
gtagaaaaca cacagctgca gaacgaaaaa ttgtacttgt actatctgca gaacggcaga2460
gacatgtacg tcgaccaaga acttgatatt aatagactgt ccgactatga cgtagaccat2520
atcgtgcccc agtccttcct gaaggacgac tccattgata acaaagtctt gacaagaagc2580
gacaagaaca ggggtaaaag tgataatgtg cctagcgagg aggtggtgaa aaaaatgaag2640
aactactggc gacagctgct taatgcaaag ctcattacac aacggaagtt cgataatctg2700
acgaaagcag agagaggtgg cttgtctgag ttggacaagg cagggtttat taagcggcag2760
ctggtggaaa ctaggcagat cacaaagcac gtggcgcaga ttttggacag ccggatgaac2820
acaaaatacg acgaaaatga taaactgata cgagaggtca aagttatcac gctgaaaagc2880
aagctggtgt ccgattttcg gaaagacttc cagttctaca aagttcgcga gattaataac2940
taccatcatg ctcacgatgc gtacctgaac gctgttgtcg ggaccgcctt gataaagaag3000
tacccaaagc tggaatccga gttcgtatac ggggattaca aagtgtacga tgtgaggaaa3060
atgatagcca agtccgagca ggagattgga aaggccacag ctaagtactt cttttattct3120
aacatcatga atttttttaa gacggaaatt accctggcca acggagagat cagaaagcgg3180
ccccttatag agacaaatgg tgaaacaggt gaaatcgtct gggataaggg cagggatttc3240
gctactgtga ggaaggtgct gagtatgcca caggtaaata tcgtgaaaaa aaccgaagta3300
cagaccggag gattttccaa ggaaagcatt ttgcctaaaa gaaactcaga caagctcatc3360
gcccgcaaga aagattggga ccctaagaaa tacgggggat ttgactcacc caccgtagcc3420
tattctgtgc tggtggtagc taaggtggaa aaaggaaagt ctaagaagct gaagtccgtg3480
aaggaactct tgggaatcac tatcatggaa agatcatcct ttgaaaagaa ccctatcgat3540
ttcctggagg ctaagggtta caaggaggtc aagaaagacc tcatcattaa actgccaaaa3600
tactctctct tcgagctgga aaatggcagg aagagaatgt tggccagcgc cggagagctg3660
caaaagggaa acgagcttgc tctgccctcc aaatatgtta attttctcta tctcgcttcc3720
cactatgaaa agctgaaagg gtctcccgaa gataacgagc agaagcagct gttcgtcgaa3780
cagcacaagc actatctgga tgaaataatc gaacaaataa gcgagttcag caaaagggtt3840
atcctggcgg atgctaattt ggacaaagta ctgtctgctt ataacaagca ccgggataag3900
cctattaggg aacaagccga gaatataatt cacctcttta cactcacgaa tctcggagcc3960
cccgccgcct tcaaatactt tgatacgact atcgaccgga aacggtatac cagtaccaaa4020
gaggtcctcg atgccaccct catccaccag tcaattactg gcctgtacga aacacggatc4080
gacctctctc aactgggcgg cgactag4107
TABLE 4 — Antigen Binding domains that bind CD19 SEQ ID
AntigenNameAmino Acid SequenceNO:
CD19muCTL019DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI160
YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPY
TFGGGTKLEITGGGGSGGGGSGGGGSEVKLQESGPGLVAPSQSLSVTC
TVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTII
KDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTV
SS
CD19huscFv1EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLI161
YHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPY
TFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTC
TVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTIS
KDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTV
SS
CD19huscFv2EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLI162
YHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPY
TFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTC
TVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYQSSLKSRVTIS
KDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTV
SS
CD19huscFv3QVQLQESGPGLVKPSETLSLICTVSGVSLPDYGVSWIRQPPGKGLEWI163
GVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCA
KHYYYGGSYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVMTQSPA
TLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSG
IPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLE
IK
CD19huscFv4QVQLQESGPGLVKPSETLSLICTVSGVSLPDYGVSWIRQPPGKGLEWI164
GVIWGSETTYYQSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCA
KHYYYGGSYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVMTQSPA
TLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSG
IPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLE
IK
CD19huscFv5EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLI165
YHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPY
TFGQGTKLEIKGGGGSGGGGSGGGGSGGGGSQVQLQESGPGLVKPSET
LSLICTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKS
RVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQG
TLVTVSS
CD19huscFv6EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLI166
YHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPY
TFGQGTKLEIKGGGGSGGGGSGGGGSGGGGSQVQLQESGPGLVKPSET
LSLICTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYQSSLKS
RVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQG
TLVTVSS
CD19huscFv7QVQLQESGPGLVKPSETLSLICTVSGVSLPDYGVSWIRQPPGKGLEWI167
GVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCA
KHYYYGGSYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVM
TQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLTYHTS
RLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQ
GTKLEIK
CD19huscFv8QVQLQESGPGLVKPSETLSLICTVSGVSLPDYGVSWIRQPPGKGLEWI168
GVIWGSETTYYQSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCA
KHYYYGGSYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVM
TQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLTYHTS
RLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQ
GTKLEIK
CD19huscFv9EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLI169
YHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPY
TFGQGTKLEIKGGGGSGGGGSGGGGSGGGGSQVQLQESGPGLVKPSET
LSLICTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYNSSLKS
RVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQG
TLVTVSS
CD19HuscFv10QVQLQESGPGLVKPSETLSLICTVSGVSLPDYGVSWIRQPPGKGLEWI170
GVIWGSETTYYNSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCA
KHYYYGGSYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVM
TQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTS
RLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQ
GTKLEIK
CD19HuscFv11EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLI171
YHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPY
TFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTC
TVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYNSSLKSRVTIS
KDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTV
SS
CD19HuscFv12QVQLQESGPGLVKPSETLSLICTVSGVSLPDYGVSWIRQPPGKGLEWI172
GVIWGSETTYYNSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCA
KHYYYGGSYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVMTQSPA
TLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSG
IPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLE
IK
TABLE 5 — Heavy Chain Variable Domain CDRs
DescriptionFWHCDR1IDHCDR2IDHCDR3ID
murine_CART19GVSLPDYGVS176VIWGSETTYYNSALKS177HYYYGGSYAMDY181
humanized_CART19 aVH4GVSLPDYGVS176VIWGSETTYY S LKS178HYYYGGSYAMDY181
humanized_CART19 bVH4GVSLPDYGVS176VIWGSETTYY S LKS179HYYYGGSYAMDY181
humanized_CART19 cVH4GVSLPDYGVS176VIWGSETTYYNS LKS180HYYYGGSYAMDY181
TABLE 6 — Light Chain Variable Domain CDRs
DescriptionFWLCDR1IDLCDR2IDLCDR3ID
murine_CART19RASQDISKYLN182HTSRLHS183QQGNTLPYT184
humanized_CART19 aVK3RASQDISKYLN182HTSRLHS183QQGNTLPYT184
humanized_CART19 bVK3RASQDISKYLN182HTSRLHS183QQGNTLPYT184
humanized_CART19 cVK3RASQDISKYLN182HTSRLHS183QQGNTLPYT184
TABLE 7 — Additional Anti-CD19 antibody binding domains Ab
NameVH SequenceVL Sequence
SJ25-C1QVQLLESGAELVRPGSSVKISCKASGELVLTQSPKFMSTSVGDRVSVTCKASQNV
YAFSSYWMNWVKQRPGQGLEWIGQIYGTNVAWYQQKPGQSPKPLIYSATYRNSGV
PGDGDTNYNGKFKGQATLTADKSSSTPDRFTGSGSGTDFTLTITNVQSKDLADYF
AYMQLSGLTSEDSAVYSCARKTISSVYFCQYNRYPYTSGGGTKLEIKRRS (SEQ
VDFYFDYWGQGTTVT (SEQ IDID NO: 174)
NO: 173)
ScFv Sequence
SJ25-C1QVQLLESGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIYPGDGD
scFvTNYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVYSCARKTISSVVDFYFDYWGQ
GTTVTGSTSGSGKPGSGEGSTKGELVLTQSPKFMSTSVGDRVSVTCKASQNVGTNVA
WYQQKPGQSPKPLIYSATYRNSGVPDRFTGSGSGTDFTLTITNVQSKDLADYFYFCQ
YNRYPYTSGGGTKLEIKRRS (SEQ ID NO: 175)
TABLE 8 — Antigen Binding domains that bind BCMA The amino acid sequences of variable heavy chain and variable light chain sequences for each scFy are also provided. SEQ
Name/ID
DescriptionNO:Sequence
139109
139109-aa249EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSG
ScFv domainIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGG
ESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDR
VTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
TDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIK
139109-nt264GAAGTGCAATTGGTGGAATCAGGGGGAGGACTTGTGCAGCCTGGAGGATC
ScFv domainGCTGAGACTGTCATGTGCCGTGTCCGGCTTTGCCCTGTCCAACCACGGGA
TGTCCTGGGTCCGCCGCGCGCCTGGAAAGGGCCTCGAATGGGTGTCGGGT
ATTGTGTACAGCGGTAGCACCTACTATGCCGCATCCGTGAAGGGGAGATT
CACCATCAGCCGGGACAACTCCAGGAACACTCTGTACCTCCAAATGAATT
CGCTGAGGCCAGAGGACACTGCCATCTACTACTGCTCCGCGCATGGCGGA
GAGTCCGACGTCTGGGGACAGGGGACCACCGTGACCGTGTCTAGCGCGTC
CGGCGGAGGCGGCAGCGGGGGTCGGGCATCAGGGGGCGGCGGATCGGACA
TCCAGCTCACCCAGTCCCCGAGCTCGCTGTCCGCCTCCGTGGGAGATCGG
GTCACCATCACGTGCCGCGCCAGCCAGTCGATTTCCTCCTACCTGAACTG
GTACCAACAGAAGCCCGGAAAAGCCCCGAAGCTTCTCATCTACGCCGCCT
CGAGCCTGCAGTCAGGAGTGCCCTCACGGTTCTCCGGCTCCGGTTCCGGT
ACTGATTTCACCCTGACCATTTCCTCCCTGCAACCGGAGGACTTCGCTAC
TTACTACTGCCAGCAGTCGTACTCCACCCCCTACACTTTCGGACAAGGCA
CCAAGGTCGAAATCAAG
139109-aa279EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSG
VHIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGG
ESDVWGQGTTVTVSS
139109-aa294DIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYA
VLASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQ
GTKVEIK
139103
139103-aa239QVQLVESGGGLVQPGRSLRLSCAASGFTFSNYAMSWVRQAPGKGLGWVSG
ScFv domainISRSGENTYYADSVKGRFTISRDNSKNTLYLQMNSLRDEDTAVYYCARSP
AHYYGGMDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIVLTQSPGTLSL
SPGERATLSCRASQSISSSFLAWYQQKPGQAPRLLIYGASRRATGIPDRF
SGSGSGTDFTLTISRLEPEDSAVYYCQQYHSSPSWTFGQGTKLEIK
139103-nt254CAAGTGCAACTCGTGGAATCTGGTGGAGGACTCGTGCAACCCGGAAGATC
ScFv domainGCTTAGACTGTCGTGTGCCGCCAGCGGGTTCACTTTCTCGAACTACGCGA
TGTCCTGGGTCCGCCAGGCACCCGGAAAGGGACTCGGTTGGGTGTCCGGC
ATTTCCCGGTCCGGCGAAAATACCTACTACGCCGACTCCGTGAAGGGCCG
CTTCACCATCTCAAGGGACAACAGCAAAAACACCCTGTACTTGCAAATGA
ACTCCCTGCGGGATGAAGATACAGCCGTGTACTATTGCGCCCGGTCGCCT
GCCCATTACTACGGCGGAATGGACGTCTGGGGACAGGGAACCACTGTGAC
TGTCAGCAGCGCGTCGGGTGGCGGCGGCTCAGGGGGTCGGGCCTCCGGGG
GGGGAGGGTCCGACATCGTGCTGACCCAGTCCCCGGGAACCCTGAGCCTG
AGCCCGGGAGAGCGCGCGACCCTGTCATGCCGGGCATCCCAGAGCATTAG
CTCCTCCTTTCTCGCCTGGTATCAGCAGAAGCCCGGACAGGCCCCGAGGC
TGCTGATCTACGGCGCTAGCAGAAGGGCTACCGGAATCCCAGACCGGTTC
TCCGGCTCCGGTTCCGGGACCGATTTCACCCTTACTATCTCGCGCCTGGA
ACCTGAGGACTCCGCCGTCTACTACTGCCAGCAGTACCACTCATCCCCGT
CGTGGACGTTCGGACAGGGCACCAAGCTGGAGATTAAG
139103-aa269QVQLVESGGGLVQPGRSLRLSCAASGFTFSNYAMSWVRQAPGKGLGWVSG
VHISRSGENTYYADSVKGRFTISRDNSKNTLYLQMNSLRDEDTAVYYCARSP
AHYYGGMDVWGQGTTVTVSS
139103-aa284DIVLTQSPGTLSLSPGERATLSCRASQSISSSFLAWYQQKPGQAPRLLIY
VLGASRRATGIPDRFSGSGSGTDFTLTISRLEPEDSAVYYCQQYHSSPSWTF
GQGTKLEIK
139105
139105-aa240QVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSG
ScFv domainISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCSVHS
FLAYWGQGTLVTVSSASGGGGSGGRASGGGGSDIVMTQTPLSLPVTPGEP
ASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFS
GSGSGTDFTLKISRVEAEDVGVYYCMQALQTPYTFGQGTKVEIK
139105-nt255CAAGTGCAACTCGTCGAATCCGGTGGAGGTCTGGTCCAACCTGGTAGAAG
ScFv domainCCTGAGACTGTCGTGTGCGGCCAGCGGATTCACCTTTGATGACTATGCTA
TGCACTGGGTGCGGCAGGCCCCAGGAAAGGGCCTGGAATGGGTGTCGGGA
ATTAGCTGGAACTCCGGGTCCATTGGCTACGCCGACTCCGTGAAGGGCCG
CTTCACCATCTCCCGCGACAACGCAAAGAACTCCCTGTACTTGCAAATGA
ACTCGCTCAGGGCTGAGGATACCGCGCTGTACTACTGCTCCGTGCATTCC
TTCCTGGCCTACTGGGGACAGGGAACTCTGGTCACCGTGTCGAGCGCCTC
CGGCGGCGGGGGCTCGGGTGGACGGGCCTCGGGCGGAGGGGGGTCCGACA
TCGTGATGACCCAGACCCCGCTGAGCTTGCCCGTGACTCCCGGAGAGCCT
GCATCCATCTCCTGCCGGTCATCCCAGTCCCTTCTCCACTCCAACGGATA
CAACTACCTCGACTGGTACCTCCAGAAGCCGGGACAGAGCCCTCAGCTTC
TGATCTACCTGGGGTCAAATAGAGCCTCAGGAGTGCCGGATCGGTTCAGC
GGATCTGGTTCGGGAACTGATTTCACTCTGAAGATTTCCCGCGTGGAAGC
CGAGGACGTGGGCGTCTACTACTGTATGCAGGCGCTGCAGACCCCCTATA
CCTTCGGCCAAGGGACGAAAGTGGAGATCAAG
139105-aa270QVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSG
VHISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCSVHS
FLAYWGQGTLVTVSS
139105-aa285DIVMTQTPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQ
VLLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTP
YTFGQGTKVEIK
139111
139111-aa241EVQLLESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSG
ScFv domainIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGG
ESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIVMTQTPLSLSVTPGQP
ASISCKSSQSLLRNDGKTPLYWYLQKAGQPPQLLIYEVSNRFSGVPDRFS
GSGSGTDFTLKISRVEAEDVGAYYCMQNIQFPSFGGGTKLEIK
139111-nt256GAAGTGCAATTGTTGGAATCTGGAGGAGGACTTGTGCAGCCTGGAGGATC
ScFv domainACTGAGACTTTCGTGTGCGGTGTCAGGCTTCGCCCTGAGCAACCACGGCA
TGAGCTGGGTGCGGAGAGCCCCGGGGAAGGGTCTGGAATGGGTGTCCGGG
ATCGTCTACTCCGGTTCAACTTACTACGCCGCAAGCGTGAAGGGTCGCTT
CACCATTTCCCGCGATAACTCCCGGAACACCCTGTACCTCCAAATGAACT
CCCTGCGGCCCGAGGACACCGCCATCTACTACTGTTCCGCGCATGGAGGA
GAGTCCGATGTCTGGGGACAGGGCACTACCGTGACCGTGTCGAGCGCCTC
GGGGGGAGGAGGCTCCGGCGGTCGCGCCTCCGGGGGGGGTGGCAGCGACA
TTGTGATGACGCAGACTCCACTCTCGCTGTCCGTGACCCCGGGACAGCCC
GCGTCCATCTCGTGCAAGAGCTCCCAGAGCCTGCTGAGGAACGACGGAAA
GACTCCTCTGTATTGGTACCTCCAGAAGGCTGGACAGCCCCCGCAACTGC
TCATCTACGAAGTGTCAAATCGCTTCTCCGGGGTGCCGGATCGGTTTTCC
GGCTCGGGATCGGGCACCGACTTCACCCTGAAAATCTCCAGGGTCGAGGC
CGAGGACGTGGGAGCCTACTACTGCATGCAAAACATCCAGTTCCCTTCCT
TCGGCGGCGGCACAAAGCTGGAGATTAAG
139111-aa271EVQLLESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSG
VHIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGG
ESDVWGQGTTVTVSS
139111-aa286DIVMTQTPLSLSVTPGQPASISCKSSQSLLRNDGKTPLYWYLQKAGQPPQ
VLLLIYEVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGAYYCMQNIQFP
SFGGGTKLEIK
139100
139100-aa242QVQLVQSGAEVRKTGASVKVSCKASGYIFDNFGINWVRQAPGQGLEWMGW
ScFv domainINPKNNNTNYAQKFQGRVTITADESTNTAYMEVSSLRSEDTAVYYCARGP
YYYQSYMDVWGQGTMVTVSSASGGGGSGGRASGGGGSDIVMTQTPLSLPV
TPGEPASISCRSSQSLLHSNGYNYLNWYLQKPGQSPQLLIYLGSKRASGV
PDRFSGSGSGTDFTLHITRVGAEDVGVYYCMQALQTPYTFGQGTKLEIK
139100-nt257CAAGTCCAACTCGTCCAGTCCGGCGCAGAAGTCAGAAAAACCGGTGCTAG
ScFv domainCGTGAAAGTGTCCTGCAAGGCCTCCGGCTACATTTTCGATAACTTCGGAA
TCAACTGGGTCAGACAGGCCCCGGGCCAGGGGCTGGAATGGATGGGATGG
ATCAACCCCAAGAACAACAACACCAACTACGCACAGAAGTTCCAGGGCCG
CGTGACTATCACCGCCGATGAATCGACCAATACCGCCTACATGGAGGTGT
CCTCCCTGCGGTCGGAGGACACTGCCGTGTATTACTGCGCGAGGGGCCCA
TACTACTACCAAAGCTACATGGACGTCTGGGGACAGGGAACCATGGTGAC
CGTGTCATCCGCCTCCGGTGGTGGAGGCTCCGGGGGGCGGGCTTCAGGAG
GCGGAGGAAGCGATATTGTGATGACCCAGACTCCGCTTAGCCTGCCCGTG
ACTCCTGGAGAACCGGCCTCCATTTCCTGCCGGTCCTCGCAATCACTCCT
GCATTCCAACGGTTACAACTACCTGAATTGGTACCTCCAGAAGCCTGGCC
AGTCGCCCCAGTTGCTGATCTATCTGGGCTCGAAGCGCGCCTCCGGGGTG
CCTGACCGGTTTAGCGGATCTGGGAGCGGCACGGACTTCACTCTCCACAT
CACCCGCGTGGGAGCGGAGGACGTGGGAGTGTACTACTGTATGCAGGCGC
TGCAGACTCCGTACACATTCGGACAGGGCACCAAGCTGGAGATCAAG
139100-aa272QVQLVQSGAEVRKTGASVKVSCKASGYIFDNFGINWVRQAPGQGLEWMGW
VHINPKNNNTNYAQKFQGRVTITADESTNTAYMEVSSLRSEDTAVYYCARGP
YYYQSYMDVWGQGTMVTVSS
139100-aa287DIVMTQTPLSLPVTPGEPASISCRSSQSLLHSNGYNYLNWYLQKPGQSPQ
VLLLIYLGSKRASGVPDRFSGSGSGTDFTLHITRVGAEDVGVYYCMQALQTP
YTFGQGTKLEIK
139101
139101-aa243QVQLQESGGGLVQPGGSLRLSCAASGFTFSSDAMTWVRQAPGKGLEWVSV
ScFv domainISGSGGTTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLD
SSGYYYARGPRYWGQGTLVTVSSASGGGGSGGRASGGGGSDIQLTQSPSS
LSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYGASTLASGVPA
RFSGSGSGTHFTLTINSLQSEDSATYYCQQSYKRASFGQGTKVEIK
139101-nt258CAAGTGCAACTTCAAGAATCAGGCGGAGGACTCGTGCAGCCCGGAGGATC
ScFv domainATTGCGGCTCTCGTGCGCCGCCTCGGGCTTCACCTTCTCGAGCGACGCCA
TGACCTGGGTCCGCCAGGCCCCGGGGAAGGGGCTGGAATGGGTGTCTGTG
ATTTCCGGCTCCGGGGGAACTACGTACTACGCCGATTCCGTGAAAGGTCG
CTTCACTATCTCCCGGGACAACAGCAAGAACACCCTTTATCTGCAAATGA
ATTCCCTCCGCGCCGAGGACACCGCCGTGTACTACTGCGCCAAGCTGGAC
TCCTCGGGCTACTACTATGCCCGGGGTCCGAGATACTGGGGACAGGGAAC
CCTCGTGACCGTGTCCTCCGCGTCCGGCGGAGGAGGGTCGGGAGGGCGGG
CCTCCGGCGGCGGCGGTTCGGACATCCAGCTGACCCAGTCCCCATCCTCA
CTGAGCGCAAGCGTGGGCGACAGAGTCACCATTACATGCAGGGCGTCCCA
GAGCATCAGCTCCTACCTGAACTGGTACCAACAGAAGCCTGGAAAGGCTC
CTAAGCTGTTGATCTACGGGGCTTCGACCCTGGCATCCGGGGTGCCCGCG
AGGTTTAGCGGAAGCGGTAGCGGCACTCACTTCACTCTGACCATTAACAG
CCTCCAGTCCGAGGATTCAGCCACTTACTACTGTCAGCAGTCCTACAAGC
GGGCCAGCTTCGGACAGGGCACTAAGGTCGAGATCAAG
139101-aa273QVQLQESGGGLVQPGGSLRLSCAASGFTFSSDAMTWVRQAPGKGLEWVSV
VHISGSGGTTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLD
SSGYYYARGPRYWGQGTLVTVSS
139101-aa288DIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYG
VLASTLASGVPARFSGSGSGTHFTLTINSLQSEDSATYYCQQSYKRASFGQG
TKVEIK
139102
139102-aa244QVQLVQSGAEVKKPGASVKVSCKASGYTFSNYGITWVRQAPGQGLEWMGW
ScFv domainISAYNGNTNYAQKFQGRVTMTRNTSISTAYMELSSLRSEDTAVYYCARGP
YYYYMDVWGKGTMVTVSSASGGGGSGGRASGGGGSEIVMTQSPLSLPVTP
GEPASISCRSSQSLLYSNGYNYVDWYLQKPGQSPQLLIYLGSNRASGVPD
RFSGSGSGTDFKLQISRVEAEDVGIYYCMQGRQFPYSFGQGTKVEIK
139102-nt259CAAGTCCAACTGGTCCAGAGCGGTGCAGAAGTGAAGAAGCCCGGAGCGAG
ScFv domainCGTGAAAGTGTCCTGCAAGGCTTCCGGGTACACCTTCTCCAACTACGGCA
TCACTTGGGTGCGCCAGGCCCCGGGACAGGGCCTGGAATGGATGGGGTGG
ATTTCCGCGTACAACGGCAATACGAACTACGCTCAGAAGTTCCAGGGTAG
AGTGACCATGACTAGGAACACCTCCATTTCCACCGCCTACATGGAACTGT
CCTCCCTGCGGAGCGAGGACACCGCCGTGTACTATTGCGCCCGGGGACCA
TACTACTACTACATGGATGTCTGGGGGAAGGGGACTATGGTCACCGTGTC
ATCCGCCTCGGGAGGCGGCGGATCAGGAGGACGCGCCTCTGGTGGTGGAG
GATCGGAGATCGTGATGACCCAGAGCCCTCTCTCCTTGCCCGTGACTCCT
GGGGAGCCCGCATCCATTTCATGCCGGAGCTCCCAGTCACTTCTCTACTC
CAACGGCTATAACTACGTGGATTGGTACCTCCAAAAGCCGGGCCAGAGCC
CGCAGCTGCTGATCTACCTGGGCTCGAACAGGGCCAGCGGAGTGCCTGAC
CGGTTCTCCGGGTCGGGAAGCGGGACCGACTTCAAGCTGCAAATCTCGAG
AGTGGAGGCCGAGGACGTGGGAATCTACTACTGTATGCAGGGCCGCCAGT
TTCCGTACTCGTTCGGACAGGGCACCAAAGTGGAAATCAAG
139102-aa274QVQLVQSGAEVKKPGASVKVSCKASGYTFSNYGITWVRQAPGQGLEWMGW
VHISAYNGNTNYAQKFQGRVTMTRNTSISTAYMELSSLRSEDTAVYYCARGP
YYYYMDVWGKGTMVTVSS
139102-aa289EIVMTQSPLSLPVTPGEPASISCRSSQSLLYSNGYNYVDWYLQKPGQSPQ
VLLLIYLGSNRASGVPDRFSGSGSGTDFKLQISRVEAEDVGIYYCMQGRQFP
YSFGQGTKVEIK
139104
139104-aa245EVQLLETGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSG
ScFv domainIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGG
ESDVWGQGTTVTVSSASGGGGSGGRASGGGGSEIVLTQSPATLSVSPGES
ATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASTRASGIPDRFSGSGSG
TDFTLTISSLQAEDVAVYYCQQYGSSLTFGGGTKVEIK
139104-nt260GAAGTGCAATTGCTCGAAACTGGAGGAGGTCTGGTGCAACCTGGAGGATC
ScFv domainACTTCGCCTGTCCTGCGCCGTGTCGGGCTTTGCCCTGTCCAACCATGGAA
TGAGCTGGGTCCGCCGCGCGCCGGGGAAGGGCCTCGAATGGGTGTCCGGC
ATCGTCTACTCCGGCTCCACCTACTACGCCGCGTCCGTGAAGGGCCGGTT
CACGATTTCACGGGACAACTCGCGGAACACCCTGTACCTCCAAATGAATT
CCCTTCGGCCGGAGGATACTGCCATCTACTACTGCTCCGCCCACGGTGGC
GAATCCGACGTCTGGGGCCAGGGAACCACCGTGACCGTGTCCAGCGCGTC
CGGGGGAGGAGGAAGCGGGGGTAGAGCATCGGGTGGAGGCGGATCAGAGA
TCGTGCTGACCCAGTCCCCCGCCACCTTGAGCGTGTCACCAGGAGAGTCC
GCCACCCTGTCATGCCGCGCCAGCCAGTCCGTGTCCTCCAACCTGGCTTG
GTACCAGCAGAAGCCGGGGCAGGCCCCTAGACTCCTGATCTATGGGGCGT
CGACCCGGGCATCTGGAATTCCCGATAGGTTCAGCGGATCGGGCTCGGGC
ACTGACTTCACTCTGACCATCTCCTCGCTGCAAGCCGAGGACGTGGCTGT
GTACTACTGTCAGCAGTACGGAAGCTCCCTGACTTTCGGTGGCGGGACCA
AAGTCGAGATTAAG
139104-aa275EVQLLETGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSG
VHIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGG
ESDVWGQGTTVTVSS
139104-aa290EIVLTQSPATLSVSPGESATLSCRASQSVSSNLAWYQQKPGQAPRLLIYG
VLASTRASGIPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYGSSLTFGGG
TKVEIK
139106
139106-aa246EVQLVETGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSG
ScFv domainIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGG
ESDVWGQGTTVTVSSASGGGGSGGRASGGGGSEIVMTQSPAILSVSPGER
ATLSCRASQSVSSKLAWYQQKPGQAPRLLMYGASIRATGIPDRFSGSGSG
TEFTLTISSLEPEDFAVYYCQQYGSSSWTFGQGTKVEIK
139106-nt261GAAGTGCAATTGGTGGAAACTGGAGGAGGACTTGTGCAACCTGGAGGATC
ScFv domainATTGAGACTGAGCTGCGCAGTGTCGGGATTCGCCCTGAGCAACCATGGAA
TGTCCTGGGTCAGAAGGGCCCCTGGAAAAGGCCTCGAATGGGTGTCAGGG
ATCGTGTACTCCGGTTCCACTTACTACGCCGCCTCCGTGAAGGGGCGCTT
CACTATCTCACGGGATAACTCCCGCAATACCCTGTACCTCCAAATGAACA
GCCTGCGGCCGGAGGATACCGCCATCTACTACTGTTCCGCCCACGGTGGA
GAGTCTGACGTCTGGGGCCAGGGAACTACCGTGACCGTGTCCTCCGCGTC
CGGCGGTGGAGGGAGCGGCGGCCGCGCCAGCGGCGGCGGAGGCTCCGAGA
TCGTGATGACCCAGAGCCCCGCTACTCTGTCGGTGTCGCCCGGAGAAAGG
GCGACCCTGTCCTGCCGGGCGTCGCAGTCCGTGAGCAGCAAGCTGGCTTG
GTACCAGCAGAAGCCGGGCCAGGCACCACGCCTGCTTATGTACGGTGCCT
CCATTCGGGCCACCGGAATCCCGGACCGGTTCTCGGGGTCGGGGTCCGGT
ACCGAGTTCACACTGACCATTTCCTCGCTCGAGCCCGAGGACTTTGCCGT
CTATTACTGCCAGCAGTACGGCTCCTCCTCATGGACGTTCGGCCAGGGGA
CCAAGGTCGAAATCAAG
139106-aa276EVQLVETGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSG
VHIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGG
ESDVWGQGTTVTVSS
139106-aa291EIVMTQSPATLSVSPGERATLSCRASQSVSSKLAWYQQKPGQAPRLLMYG
VLASIRATGIPDRFSGSGSGTEFTLTISSLEPEDFAVYYCQQYGSSSWTFGQ
GTKVEIK
139107
139107-aa247EVQLVETGGGVVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSG
ScFv domainIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGG
ESDVWGQGTTVTVSSASGGGGSGGRASGGGGSEIVLTQSPGTLSLSPGER
ATLSCRASQSVGSTNLAWYQQKPGQAPRLLIYDASNRATGIPDRFSGGGS
GTDFTLTISRLEPEDFAVYYCQQYGSSPPWTFGQGTKVEIK
139107-nt262GAAGTGCAATTGGTGGAGACTGGAGGAGGAGTGGTGCAACCTGGAGGAAG
ScFv domainCCTGAGACTGTCATGCGCGGTGTCGGGCTTCGCCCTCTCCAACCACGGAA
TGTCCTGGGTCCGCCGGGCCCCTGGGAAAGGACTTGAATGGGTGTCCGGC
ATCGTGTACTCGGGTTCCACCTACTACGCGGCCTCAGTGAAGGGCCGGTT
TACTATTAGCCGCGACAACTCCAGAAACACACTGTACCTCCAAATGAACT
CGCTGCGGCCGGAAGATACCGCTATCTACTACTGCTCCGCCCATGGGGGA
GAGTCGGACGTCTGGGGACAGGGCACCACTGTCACTGTGTCCAGCGCTTC
CGGCGGTGGTGGAAGCGGGGGACGGGCCTCAGGAGGCGGTGGCAGCGAGA
TTGTGCTGACCCAGTCCCCCGGGACCCTGAGCCTGTCCCCGGGAGAAAGG
GCCACCCTCTCCTGTCGGGCATCCCAGTCCGTGGGGTCTACTAACCTTGC
ATGGTACCAGCAGAAGCCCGGCCAGGCCCCTCGCCTGCTGATCTACGACG
CGTCCAATAGAGCCACCGGCATCCCGGATCGCTTCAGCGGAGGCGGATCG
GGCACCGACTTCACCCTCACCATTTCAAGGCTGGAACCGGAGGACTTCGC
CGTGTACTACTGCCAGCAGTATGGTTCGTCCCCACCCTGGACGTTCGGCC
AGGGGACTAAGGTCGAGATCAAG
139107-aa277EVQLVETGGGVVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSG
VHIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGG
ESDVWGQGTTVTVSS
139107-aa292EIVLTQSPGTLSLSPGERATLSCRASQSVGSTNLAWYQQKPGQAPRLLIY
VLDASNRATGIPDRFSGGGSGTDFTLTISRLEPEDFAVYYCQQYGSSPPWTF
GQGTKVEIK
139108
139108-aa248QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSY
ScFv domainISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARES
GDGMDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQMTQSPSSLSASVG
DRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSG
SGTDFTLTISSLQPEDFATYYCQQSYTLAFGQGTKVDIK
139108-nt263CAAGTGCAACTCGTGGAATCTGGTGGAGGACTCGTGAAACCTGGAGGATC
ScFv domainATTGAGACTGTCATGCGCGGCCTCGGGATTCACGTTCTCCGATTACTACA
TGAGCTGGATTCGCCAGGCTCCGGGGAAGGGACTGGAATGGGTGTCCTAC
ATTTCCTCATCCGGCTCCACCATCTACTACGCGGACTCCGTGAAGGGGAG
ATTCACCATTAGCCGCGATAACGCCAAGAACAGCCTGTACCTTCAGATGA
ACTCCCTGCGGGCTGAAGATACTGCCGTCTACTACTGCGCAAGGGAGAGC
GGAGATGGGATGGACGTCTGGGGACAGGGTACCACTGTGACCGTGTCGTC
GGCCTCCGGCGGAGGGGGTTCGGGTGGAAGGGCCAGCGGCGGCGGAGGCA
GCGACATCCAGATGACCCAGTCCCCCTCATCGCTGTCCGCCTCCGTGGGC
GACCGCGTCACCATCACATGCCGGGCCTCACAGTCGATCTCCTCCTACCT
CAATTGGTATCAGCAGAAGCCCGGAAAGGCCCCTAAGCTTCTGATCTACG
CAGCGTCCTCCCTGCAATCCGGGGTCCCATCTCGGTTCTCCGGCTCGGGC
AGCGGTACCGACTTCACTCTGACCATCTCGAGCCTGCAGCCGGAGGACTT
CGCCACTTACTACTGTCAGCAAAGCTACACCCTCGCGTTTGGCCAGGGCA
CCAAAGTGGACATCAAG
139108-aa278QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSY
VHISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARES
GDGMDVWGQGTTVTVSS
139108-aa293DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYA
VLASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTLAFGQGT
KVDIK
139110
139110-aa250QVQLVQSGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSY
ScFv domainISSSGNTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARST
MVREDYWGQGTLVTVSSASGGGGSGGRASGGGGSDIVLTQSPLSLPVTLG
QPASISCKSSESLVHNSGKTYLNWFHQRPGQSPRRLIYEVSNRDSGVPDR
FTGSGSGTDFTLKISRVEAEDVGVYYCMQGTHWPGTFGQGTKLEIK
139110-nt265CAAGTGCAACTGGTGCAAAGCGGAGGAGGATTGGTCAAACCCGGAGGAAG
ScFv domainCCTGAGACTGTCATGCGCGGCCTCTGGATTCACCTTCTCCGATTACTACA
TGTCATGGATCAGACAGGCCCCGGGGAAGGGCCTCGAATGGGTGTCCTAC
ATCTCGTCCTCCGGGAACACCATCTACTACGCCGACAGCGTGAAGGGCCG
CTTTACCATTTCCCGCGACAACGCAAAGAACTCGCTGTACCTTCAGATGA
ATTCCCTGCGGGCTGAAGATACCGCGGTGTACTATTGCGCCCGGTCCACT
ATGGTCCGGGAGGACTACTGGGGACAGGGCACACTCGTGACCGTGTCCAG
CGCGAGCGGGGGTGGAGGCAGCGGTGGACGCGCCTCCGGCGGCGGCGGTT
CAGACATCGTGCTGACTCAGTCGCCCCTGTCGCTGCCGGTCACCCTGGGC
CAACCGGCCTCAATTAGCTGCAAGTCCTCGGAGAGCCTGGTGCACAACTC
AGGAAAGACTTACCTGAACTGGTTCCATCAGCGGCCTGGACAGTCCCCAC
GGAGGCTCATCTATGAAGTGTCCAACAGGGATTCGGGGGTGCCCGACCGC
TTCACTGGCTCCGGGTCCGGCACCGACTTCACCTTGAAAATCTCCAGAGT
GGAAGCCGAGGACGTGGGCGTGTACTACTGTATGCAGGGTACCCACTGGC
CTGGAACCTTTGGACAAGGAACTAAGCTCGAGATTAAG
139110-aa280QVQLVQSGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSY
VHISSSGNTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARST
MVREDYWGQGTLVTVSS
139110-aa295DIVLTQSPLSLPVTLGQPASISCKSSESLVHNSGKTYLNWFHQRPGQSPR
VLRLIYEVSNRDSGVPDRFTGSGSGTDFTLKISRVEAEDVGVYYCMQGTHWP
GTFGQGTKLEIK
139112
139112-aa251QVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSG
ScFv domainIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGG
ESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIRLTQSPSPLSASVGDR
VTITCQASEDINKFLNWYHQTPGKAPKLLIYDASTLQTGVPSRFSGSGSG
TDFTLTINSLQPEDIGTYYCQQYESLPLTFGGGTKVEIK
139112-nt266CAAGTGCAACTCGTGGAATCTGGTGGAGGACTCGTGCAACCCGGTGGAAG
ScFv domainCCTTAGGCTGTCGTGCGCCGTCAGCGGGTTTGCTCTGAGCAACCATGGAA
TGTCCTGGGTCCGCCGGGCACCGGGAAAAGGGCTGGAATGGGTGTCCGGC
ATCGTGTACAGCGGGTCAACCTATTACGCCGCGTCCGTGAAGGGCAGATT
CACTATCTCAAGAGACAACAGCCGGAACACCCTGTACTTGCAAATGAATT
CCCTGCGCCCCGAGGACACCGCCATCTACTACTGCTCCGCCCACGGAGGA
GAGTCGGACGTGTGGGGCCAGGGAACGACTGTGACTGTGTCCAGCGCATC
AGGAGGGGGTGGTTCGGGCGGCCGGGCCTCGGGGGGAGGAGGTTCCGACA
TTCGGCTGACCCAGTCCCCGTCCCCACTGTCGGCCTCCGTCGGCGACCGC
GTGACCATCACTTGTCAGGCGTCCGAGGACATTAACAAGTTCCTGAACTG
GTACCACCAGACCCCTGGAAAGGCCCCCAAGCTGCTGATCTACGATGCCT
CGACCCTTCAAACTGGAGTGCCTAGCCGGTTCTCCGGGTCCGGCTCCGGC
ACTGATTTCACTCTGACCATCAACTCATTGCAGCCGGAAGATATCGGGAC
CTACTATTGCCAGCAGTACGAATCCCTCCCGCTCACATTCGGCGGGGGAA
CCAAGGTCGAGATTAAG
139112-aa281QVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSG
VHIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGG
ESDVWGQGTTVTVSS
139112-aa296DIRLTQSPSPLSASVGDRVTITCQASEDINKFLNWYHQTPGKAPKLLIYD
VLASTLQTGVPSRFSGSGSGTDFTLTINSLQPEDIGTYYCQQYESLPLTFGG
GTKVEIK
139113
139113-aa252EVQLVETGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSG
ScFv domainIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGG
ESDVWGQGTTVTVSSASGGGGSGGRASGGGGSETTLTQSPAILSVSPGER
ATLSCRASQSVGSNLAWYQQKPGQGPRLLIYGASTRATGIPARFSGSGSG
TEFTLTISSLQPEDFAVYYCQQYNDWLPVTFGQGTKVEIK
139113-nt267GAAGTGCAATTGGTGGAAACTGGAGGAGGACTTGTGCAACCTGGAGGATC
ScFv domainATTGCGGCTCTCATGCGCTGTCTCCGGCTTCGCCCTGTCAAATCACGGGA
TGTCGTGGGTCAGACGGGCCCCGGGAAAGGGTCTGGAATGGGTGTCGGGG
ATTGTGTACAGCGGCTCCACCTACTACGCCGCTTCGGTCAAGGGCCGCTT
CACTATTTCACGGGACAACAGCCGCAACACCCTCTATCTGCAAATGAACT
CTCTCCGCCCGGAGGATACCGCCATCTACTACTGCTCCGCACACGGCGGC
GAATCCGACGTGTGGGGACAGGGAACCACTGTCACCGTGTCGTCCGCATC
CGGTGGCGGAGGATCGGGTGGCCGGGCCTCCGGGGGCGGCGGCAGCGAGA
CTACCCTGACCCAGTCCCCTGCCACTCTGTCCGTGAGCCCGGGAGAGAGA
GCCACCCTTAGCTGCCGGGCCAGCCAGAGCGTGGGCTCCAACCTGGCCTG
GTACCAGCAGAAGCCAGGACAGGGTCCCAGGCTGCTGATCTACGGAGCCT
CCACTCGCGCGACCGGCATCCCCGCGAGGTTCTCCGGGTCGGGTTCCGGG
ACCGAGTTCACCCTGACCATCTCCTCCCTCCAACCGGAGGACTTCGCGGT
GTACTACTGTCAGCAGTACAACGATTGGCTGCCCGTGACATTTGGACAGG
GGACGAAGGTGGAAATCAAA
139113-aa282EVQLVETGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSG
VHIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGG
ESDVWGQGTTVTVSS
139113-aa297ETTLTQSPATLSVSPGERATLSCRASQSVGSNLAWYQQKPGQGPRLLIYG
VLASTRATGIPARFSGSGSGTEFTLTISSLQPEDFAVYYCQQYNDWLPVTFG
QGTKVEIK
139114
139114-aa253EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSG
ScFv domainIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGG
ESDVWGQGTTVTVSSASGGGGSGGRASGGGGSEIVLTQSPGTLSLSPGER
ATLSCRASQSIGSSSLAWYQQKPGQAPRLLMYGASSRASGIPDRFSGSGS
GTDFTLTISRLEPEDFAVYYCQQYAGSPPFTFGQGTKVEIK
139114-nt268GAAGTGCAATTGGTGGAATCTGGTGGAGGACTTGTGCAACCTGGAGGATC
ScFv domainACTGAGACTGTCATGCGCGGTGTCCGGTTTTGCCCTGAGCAATCATGGGA
TGTCGTGGGTCCGGCGCGCCCCCGGAAAGGGTCTGGAATGGGTGTCGGGT
ATCGTCTACTCCGGGAGCACTTACTACGCCGCGAGCGTGAAGGGCCGCTT
CACCATTTCCCGCGATAACTCCCGCAACACCCTGTACTTGCAAATGAACT
CGCTCCGGCCTGAGGACACTGCCATCTACTACTGCTCCGCACACGGAGGA
GAATCCGACGTGTGGGGCCAGGGAACTACCGTGACCGTCAGCAGCGCCTC
CGGCGGCGGGGGCTCAGGCGGACGGGCTAGCGGCGGCGGTGGCTCCGAGA
TCGTGCTGACCCAGTCGCCTGGCACTCTCTCGCTGAGCCCCGGGGAAAGG
GCAACCCTGTCCTGTCGGGCCAGCCAGTCCATTGGATCATCCTCCCTCGC
CTGGTATCAGCAGAAACCGGGACAGGCTCCGCGGCTGCTTATGTATGGGG
CCAGCTCAAGAGCCTCCGGCATTCCCGACCGGTTCTCCGGGTCCGGTTCC
GGCACCGATTTCACCCTGACTATCTCGAGGCTGGAGCCAGAGGACTTCGC
CGTGTACTACTGCCAGCAGTACGCGGGGTCCCCGCCGTTCACGTTCGGAC
AGGGAACCAAGGTCGAGATCAAG
139114-aa283EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSG
VHIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGG
ESDVWGQGTTVTVSS
139114-aa298EIVLTQSPGILSLSPGERATLSCRASQSIGSSSLAWYQQKPGQAPRLLMY
VLGASSRASGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYAGSPPFTF
GQGTKVEIK
149362
149362-aa329QVQLQESGPGLVKPSETLSLTCTVSGGSISSSYYYWGWIRQPPGKGLEWI
ScFv domainGSIYYSGSAYYNPSLKSRVTISVDTSKNQFSLRLSSVTAADTAVYYCARH
WQEWPDAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSETTLTQSPAFMSAT
PGDKVIISCKASQDIDDAMNWYQQKPGEAPLFIIQSATSPVPGIPPRFSG
SGFGTDFSLTINNIESEDAAYYFCLQHDNFPLTFGQGTKLEIK
149362-nt350CAAGTGCAGCTTCAGGAAAGCGGACCGGGCCTGGTCAAGCCATCCGAAAC
ScFv domainTCTCTCCCTGACTTGCACTGTGTCTGGCGGTTCCATCTCATCGTCGTACT
ACTACTGGGGCTGGATTAGGCAGCCGCCCGGAAAGGGACTGGAGTGGATC
GGAAGCATCTACTATTCCGGCTCGGCGTACTACAACCCTAGCCTCAAGTC
GAGAGTGACCATCTCCGTGGATACCTCCAAGAACCAGTTTTCCCTGCGCC
TGAGCTCCGTGACCGCCGCTGACACCGCCGTGTACTACTGTGCTCGGCAT
TGGCAGGAATGGCCCGATGCCTTCGACATTTGGGGCCAGGGCACTATGGT
CACTGTGTCATCCGGGGGTGGAGGCAGCGGGGGAGGAGGGTCCGGGGGGG
GAGGTTCAGAGACAACCTTGACCCAGTCACCCGCATTCATGTCCGCCACT
CCGGGAGACAAGGTCATCATCTCGTGCAAAGCGTCCCAGGATATCGACGA
TGCCATGAATTGGTACCAGCAGAAGCCTGGCGAAGCGCCGCTGTTCATTA
TCCAATCCGCAACCTCGCCCGTGCCTGGAATCCCACCGCGGTTCAGCGGC
AGCGGTTTCGGAACCGACTTTTCCCTGACCATTAACAACATTGAGTCCGA
GGACGCCGCCTACTACTTCTGCCTGCAACACGACAACTTCCCTCTCACGT
TCGGCCAGGGAACCAAGCTGGAAATCAAG
149362-aa VH371QVQLQESGPGLVKPSETLSLTCTVSGGSISSSYYYWGWIRQPPGKGLEWI
GSIYYSGSAYYNPSLKSRVTISVDTSKNQFSLRLSSVTAADTAVYYCARH
WQEWPDAFDIWGQGTMVTVSS
149362-aa VL392ETTLTQSPAFMSATPGDKVIISCKASQDIDDAMNWYQQKPGEAPLFIIQS
ATSPVPGIPPRFSGSGFGTDFSLTINNIESEDAAYYFCLQHDNFPLTFGQ
GTKLEIK
149363
149363-aa330QVNLRESGPALVKPTQTLTLTCTFSGFSLRTSGMCVSWIRQPPGKALEWL
ScFv domainARIDWDEDKFYSTSLKTRLTISKDTSDNQVVLRMTNMDPADTATYYCARS
GAGGTSATAFDIWGPGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLS
ASVGDRVTITCRASQDIYNNLAWFQLKPGSAPRSLMYAANKSQSGVPSRF
SGSASGTDFTLTISSLQPEDFATYYCQHYYRFPYSFGQGTKLEIK
149363-nt351CAAGTCAATCTGCGCGAATCCGGCCCCGCCTTGGTCAAGCCTACCCAGAC
ScFv domainCCTCACTCTGACCTGTACTTTCTCCGGCTTCTCCCTGCGGACTTCCGGGA
TGTGCGTGTCCTGGATCAGACAGCCTCCGGGAAAGGCCCTGGAGTGGCTC
GCTCGCATTGACTGGGATGAGGACAAGTTCTACTCCACCTCACTCAAGAC
CAGGCTGACCATCAGCAAAGATACCTCTGACAACCAAGTGGTGCTCCGCA
TGACCAACATGGACCCAGCCGACACTGCCACTTACTACTGCGCGAGGAGC
GGAGCGGGCGGAACCTCCGCCACCGCCTTCGATATTTGGGGCCCGGGTAC
CATGGTCACCGTGTCAAGCGGAGGAGGGGGGTCCGGGGGCGGCGGTTCCG
GGGGAGGCGGATCGGACATTCAGATGACTCAGTCACCATCGTCCCTGAGC
GCTAGCGTGGGCGACAGAGTGACAATCACTTGCCGGGCATCCCAGGACAT
CTATAACAACCTTGCGTGGTTCCAGCTGAAGCCTGGTTCCGCACCGCGGT
CACTTATGTACGCCGCCAACAAGAGCCAGTCGGGAGTGCCGTCCCGGTTT
TCCGGTTCGGCCTCGGGAACTGACTTCACCCTGACGATCTCCAGCCTGCA
ACCCGAGGATTTCGCCACCTACTACTGCCAGCACTACTACCGCTTTCCCT
ACTCGTTCGGACAGGGAACCAAGCTGGAAATCAAG
149363-aa VH372QVNLRESGPALVKPTQTLTLICTFSGFSLRTSGMCVSWIRQPPGKALEWL
ARIDWDEDKFYSTSLKTRLTISKDTSDNQVVLRMTNMDPADTATYYCARS
GAGGTSATAFDIWGPGTMVTVSS
149363-aa VL393DIQMTQSPSSLSASVGDRVTITCRASQDIYNNLAWFQLKPGSAPRSLMYA
ANKSQSGVPSRFSGSASGTDFTLTISSLQPEDFATYYCQHYYRFPYSFGQ
GTKLEIK
149364
149364-aa331EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSS
ScFv domainISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAKTI
AAVYAFDIWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPLSLPVTPE
EPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDR
FSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPYTFGQGTKLEIK
149364-nt352GAAGTGCAGCTTGTCGAATCCGGGGGGGGACTGGTCAAGCCGGGCGGATC
ScFv domainACTGAGACTGTCCTGCGCCGCGAGCGGCTTCACGTTCTCCTCCTACTCCA
TGAACTGGGTCCGCCAAGCCCCCGGGAAGGGACTGGAATGGGTGTCCTCT
ATCTCCTCGTCGTCGTCCTACATCTACTACGCCGACTCCGTGAAGGGAAG
ATTCACCATTTCCCGCGACAACGCAAAGAACTCACTGTACTTGCAAATGA
ACTCACTCCGGGCCGAAGATACTGCTGTGTACTATTGCGCCAAGACTATT
GCCGCCGTCTACGCTTTCGACATCTGGGGCCAGGGAACCACCGTGACTGT
GTCGTCCGGTGGTGGTGGCTCGGGCGGAGGAGGAAGCGGCGGCGGGGGGT
CCGAGATTGTGCTGACCCAGTCGCCACTGAGCCTCCCTGTGACCCCCGAG
GAACCCGCCAGCATCAGCTGCCGGTCCAGCCAGTCCCTGCTCCACTCCAA
CGGATACAATTACCTCGATTGGTACCTTCAGAAGCCTGGACAAAGCCCGC
AGCTGCTCATCTACTTGGGATCAAACCGCGCGTCAGGAGTGCCTGACCGG
TTCTCCGGCTCGGGCAGCGGTACCGATTTCACCCTGAAAATCTCCAGGGT
GGAGGCAGAGGACGTGGGAGTGTATTACTGTATGCAGGCGCTGCAGACTC
CGTACACATTTGGGCAGGGCACCAAGCTGGAGATCAAG
149364-aa VH373EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSS
ISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAKTI
AAVYAFDIWGQGTTVTVSS
149364-aa VL394EIVLTQSPLSLPVTPEEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQ
LLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTP
YTFGQGTKLEIK
149365
149365-aa332EVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSY
ScFv domainISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDL
RGAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSSYVLTQSPSVSAAPGYTA
TISCGGNNIGTKSVHWYQQKPGQAPLLVIRDDSVRPSKIPGRFSGSNSGN
MATLTISGVQAGDEADFYCQVWDSDSEHVVFGGGTKLTVL
149365-nt353GAAGTCCAGCTCGTGGAGTCCGGCGGAGGCCTTGTGAAGCCTGGAGGTTC
ScFv domainGCTGAGACTGTCCTGCGCCGCCTCCGGCTTCACCTTCTCCGACTACTACA
TGTCCTGGATCAGACAGGCCCCGGGAAAGGGCCTGGAATGGGTGTCCTAC
ATCTCGTCATCGGGCAGCACTATCTACTACGCGGACTCAGTGAAGGGGCG
GTTCACCATTTCCCGGGATAACGCGAAGAACTCGCTGTATCTGCAAATGA
ACTCACTGAGGGCCGAGGACACCGCCGTGTACTACTGCGCCCGCGATCTC
CGCGGGGCATTTGACATCTGGGGACAGGGAACCATGGTCACAGTGTCCAG
CGGAGGGGGAGGATCGGGTGGCGGAGGTTCCGGGGGTGGAGGCTCCTCCT
ACGTGCTGACTCAGAGCCCAAGCGTCAGCGCTGCGCCCGGTTACACGGCA
ACCATCTCCTGTGGCGGAAACAACATTGGGACCAAGTCTGTGCACTGGTA
TCAGCAGAAGCCGGGCCAAGCTCCCCTGTTGGTGATCCGCGATGACTCCG
TGCGGCCTAGCAAAATTCCGGGACGGTTCTCCGGCTCCAACAGCGGCAAT
ATGGCCACTCTCACCATCTCGGGAGTGCAGGCCGGAGATGAAGCCGACTT
CTACTGCCAAGTCTGGGACTCAGACTCCGAGCATGTGGTGTTCGGGGGCG
GAACCAAGCTGACTGTGCTC
149365-aa VH374EVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSY
ISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDL
RGAFDIWGQGTMVTVSS
149365-aa VL395SYVLTQSPSVSAAPGYTATISCGGNNIGTKSVHWYQQKPGQAPLLVIRDD
SVRPSKIPGRFSGSNSGNMATLTISGVQAGDEADFYCQVWDSDSEHVVFG
GGTKLTVL
149366
149366-aa333QVQLVQSGAEVKKPGASVKVSCKPSGYTVTSHYIHWVRRAPGQGLEWMGM
ScFv domainINPSGGVTAYSQTLQGRVTMTSDTSSSTVYMELSSLRSEDTAMYYCAREG
SGSGWYFDFWGRGTLVTVSSGGGGSGGGGSGGGGSSYVLTQPPSVSVSPG
QTASITCSGDGLSKKYVSWYQQKAGQSPVVLISRDKERPSGIPDRFSGSN
SADTATLTISGTQAMDEADYYCQAWDDTTVVFGGGTKLTVL
149366-nt354CAAGTGCAGCTGGTGCAGAGCGGGGCCGAAGTCAAGAAGCCGGGAGCCTC
ScFv domainCGTGAAAGTGTCCTGCAAGCCTTCGGGATACACCGTGACCTCCCACTACA
TTCATTGGGTCCGCCGCGCCCCCGGCCAAGGACTCGAGTGGATGGGCATG
ATCAACCCTAGCGGCGGAGTGACCGCGTACAGCCAGACGCTGCAGGGACG
CGTGACTATGACCTCGGATACCTCCTCCTCCACCGTCTATATGGAACTGT
CCAGCCTGCGGTCCGAGGATACCGCCATGTACTACTGCGCCCGGGAAGGA
TCAGGCTCCGGGTGGTATTTCGACTTCTGGGGAAGAGGCACCCTCGTGAC
TGTGTCATCTGGGGGAGGGGGTTCCGGTGGTGGCGGATCGGGAGGAGGCG
GTTCATCCTACGTGCTGACCCAGCCACCCTCCGTGTCCGTGAGCCCCGGC
CAGACTGCATCGATTACATGTAGCGGCGACGGCCTCTCCAAGAAATACGT
GTCGTGGTACCAGCAGAAGGCCGGACAGAGCCCGGTGGTGCTGATCTCAA
GAGATAAGGAGCGGCCTAGCGGAATCCCGGACAGGTTCTCGGGTTCCAAC
TCCGCGGACACTGCTACTCTGACCATCTCGGGGACCCAGGCTATGGACGA
AGCCGATTACTACTGCCAAGCCTGGGACGACACTACTGTCGTGTTTGGAG
GGGGCACCAAGTTGACCGTCCTT
149366-aa VH375QVQLVQSGAEVKKPGASVKVSCKPSGYTVTSHYIHWVRRAPGQGLEWMGM
INPSGGVTAYSQTLQGRVTMTSDTSSSTVYMELSSLRSEDTAMYYCAREG
SGSGWYFDFWGRGTLVTVSS
149366-aa VL396SYVLTQPPSVSVSPGQTASITCSGDGLSKKYVSWYQQKAGQSPVVLISRD
KERPSGIPDRFSGSNSADTATLTISGTQAMDEADYYCQAWDDTTVVFGGG
TKLTVL
149367
149367-aa334QVQLQESGPGLVKPSQTLSLICTVSGGSISSGGYYWSWIRQHPGKGLEWI
ScFv domainGYIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARA
GIAARLRGAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIVMTQSPSSVS
ASVGDRVIITCRASQGIRNWLAWYQQKPGKAPNLLIYAASNLQSGVPSRF
SGSGSGADFTLTISSLQPEDVATYYCQKYNSAPFTFGPGTKVDIK
149367-nt355CAAGTGCAGCTTCAGGAGAGCGGCCCGGGACTCGTGAAGCCGTCCCAGAC
ScFv domainCCTGTCCCTGACTTGCACCGTGTCGGGAGGAAGCATCTCGAGCGGAGGCT
ACTATTGGTCGTGGATTCGGCAGCACCCTGGAAAGGGCCTGGAATGGATC
GGCTACATCTACTACTCCGGCTCGACCTACTACAACCCATCGCTGAAGTC
CAGAGTGACAATCTCAGTGGACACGTCCAAGAATCAGTTCAGCCTGAAGC
TCTCTTCCGTGACTGCGGCCGACACCGCCGTGTACTACTGCGCACGCGCT
GGAATTGCCGCCCGGCTGAGGGGTGCCTTCGACATTTGGGGACAGGGCAC
CATGGTCACCGTGTCCTCCGGCGGCGGAGGTTCCGGGGGTGGAGGCTCAG
GAGGAGGGGGGTCCGACATCGTCATGACTCAGTCGCCCTCAAGCGTCAGC
GCGTCCGTCGGGGACAGAGTGATCATCACCTGTCGGGCGTCCCAGGGAAT
TCGCAACTGGCTGGCCTGGTATCAGCAGAAGCCCGGAAAGGCCCCCAACC
TGTTGATCTACGCCGCCTCAAACCTCCAATCCGGGGTGCCGAGCCGCTTC
AGCGGCTCCGGTTCGGGTGCCGATTTCACTCTGACCATCTCCTCCCTGCA
ACCTGAAGATGTGGCTACCTACTACTGCCAAAAGTACAACTCCGCACCTT
TTACTTTCGGACCGGGGACCAAAGTGGACATTAAG
149367-aa VH376QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHPGKGLEWI
GYIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARA
GIAARLRGAFDIWGQGTMVTVSS
149367-aa VL397DIVMTQSPSSVSASVGDRVIITCRASQGIRNWLAWYQQKPGKAPNLLIYA
ASNLQSGVPSRFSGSGSGADFTLTISSLQPEDVATYYCQKYNSAPFTFGP
GTKVDIK
149368
149368-aa335QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGG
ScFv domainIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARRG
GYQLLRWDVGLLRSAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSSYVLIQ
PPSVSVAPGQTARITCGGNNIGSKSVHWYQQKPGQAPVLVLYGKNNRPSG
VPDRFSGSRSGTTASLTITGAQAEDEADYYCSSRDSSGDHLRVFGTGTKV
TVL
149368-nt356CAAGTGCAGCTGGTCCAGTCGGGCGCCGAGGTCAAGAAGCCCGGGAGCTC
ScFv domainTGTGAAAGTGTCCTGCAAGGCCTCCGGGGGCACCTTTAGCTCCTACGCCA
TCTCCTGGGTCCGCCAAGCACCGGGTCAAGGCCTGGAGTGGATGGGGGGA
ATTATCCCTATCTTCGGCACTGCCAACTACGCCCAGAAGTTCCAGGGACG
CGTGACCATTACCGCGGACGAATCCACCTCCACCGCTTATATGGAGCTGT
CCAGCTTGCGCTCGGAAGATACCGCCGTGTACTACTGCGCCCGGAGGGGT
GGATACCAGCTGCTGAGATGGGACGTGGGCCTCCTGCGGTCGGCGTTCGA
CATCTGGGGCCAGGGCACTATGGTCACTGTGTCCAGCGGAGGAGGCGGAT
CGGGAGGCGGCGGATCAGGGGGAGGCGGTTCCAGCTACGTGCTTACTCAA
CCCCCTTCGGTGTCCGTGGCCCCGGGACAGACCGCCAGAATCACTTGCGG
AGGAAACAACATTGGGTCCAAGAGCGTGCATTGGTACCAGCAGAAGCCAG
GACAGGCCCCTGTGCTGGTGCTCTACGGGAAGAACAATCGGCCCAGCGGA
GTGCCGGACAGGTTCTCGGGTTCACGCTCCGGTACAACCGCTTCACTGAC
TATCACCGGGGCCCAGGCAGAGGATGAAGCGGACTACTACTGTTCCTCCC
GGGATTCATCCGGCGACCACCTCCGGGTGTTCGGAACCGGAACGAAGGTC
ACCGTGCTG
149368-aa VH377QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGG
IIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARRG
GYQLLRWDVGLLRSAFDIWGQGTMVTVSS
149368-aa VL398SYVLTQPPSVSVAPGQTARITCGGNNIGSKSVHWYQQKPGQAPVLVLYGK
NNRPSGVPDRFSGSRSGTTASLTITGAQAEDEADYYCSSRDSSGDHLRVF
GTGTKVTVL
149369
149369-aa336EVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWL
ScFv domainGRTYYRSKWYSFYAISLKSRIIINPDTSKNQFSLQLKSVTPEDTAVYYCA
RSSPEGLFLYWFDPWGQGTLVTVSSGGDGSGGGGSGGGGSSSELTQDPAV
SVALGQTIRITCQGDSLGNYYATWYQQKPGQAPVLVIYGTNNRPSGIPDR
FSASSSGNTASLTITGAQAEDEADYYCNSRDSSGHHLLFGTGTKVTVL
149369-nt357GAAGTGCAGCTCCAACAGTCAGGACCGGGGCTCGTGAAGCCATCCCAGAC
ScFv domainCCTGTCCCTGACTTGTGCCATCTCGGGAGATAGCGTGTCATCGAACTCCG
CCGCCTGGAACTGGATTCGGCAGAGCCCGTCCCGCGGACTGGAGTGGCTT
GGAAGGACCTACTACCGGTCCAAGTGGTACTCTTTCTACGCGATCTCGCT
GAAGTCCCGCATTATCATTAACCCTGATACCTCCAAGAATCAGTTCTCCC
TCCAACTGAAATCCGTCACCCCCGAGGACACAGCAGTGTATTACTGCGCA
CGGAGCAGCCCCGAAGGACTGTTCCTGTATTGGTTTGACCCCTGGGGCCA
GGGGACTCTTGTGACCGTGTCGAGCGGCGGAGATGGGTCCGGTGGCGGTG
GTTCGGGGGGCGGCGGATCATCATCCGAACTGACCCAGGACCCGGCTGTG
TCCGTGGCGCTGGGACAAACCATCCGCATTACGTGCCAGGGAGACTCCCT
GGGCAACTACTACGCCACTTGGTACCAGCAGAAGCCGGGCCAAGCCCCTG
TGTTGGTCATCTACGGGACCAACAACAGACCTTCCGGCATCCCCGACCGG
TTCAGCGCTTCGTCCTCCGGCAACACTGCCAGCCTGACCATCACTGGAGC
GCAGGCCGAAGATGAGGCCGACTACTACTGCAACAGCAGAGACTCCTCGG
GTCATCACCTCTTGTTCGGAACTGGAACCAAGGTCACCGTGCTG
149369-aa VH378EVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWL
GRTYYRSKWYSFYAISLKSRIIINPDTSKNQFSLQLKSVTPEDTAVYYCA
RSSPEGLFLYWFDPWGQGTLVTVSS
149369-aa VL399SSELTQDPAVSVALGQTIRITCQGDSLGNYYATWYQQKPGQAPVLVIYGT
NNRPSGIPDRFSASSSGNTASLTITGAQAEDEADYYCNSRDSSGHHLLFG
TGTKVTVL
BCMA_EBB-C1978-A4
BCMA_EBB-337EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1978-A4-aaISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVE
ScFv domainGSGSLDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVMTQSPGTLSLSPGE
RATLSCRASQSVSSAYLAWYQQKPGQPPRLLISGASTRATGIPDRFGGSG
SGTDFTLTISRLEPEDFAVYYCQHYGSSFNGSSLFTFGQGTRLEIK
BCMA_EBB-358GAAGTGCAGCTCGTGGAGTCAGGAGGCGGCCTGGTCCAGCCGGGAGGGTC
C1978-A4-ntCCTTAGACTGTCATGCGCCGCAAGCGGATTCACTTTCTCCTCCTATGCCA
ScFv domainTGAGCTGGGTCCGCCAAGCCCCCGGAAAGGGACTGGAATGGGTGTCCGCC
ATCTCGGGGTCTGGAGGCTCAACTTACTACGCTGACTCCGTGAAGGGACG
GTTCACCATTAGCCGCGACAACTCCAAGAACACCCTCTACCTCCAAATGA
ACTCCCTGCGGGCCGAGGATACCGCCGTCTACTACTGCGCCAAAGTGGAA
GGTTCAGGATCGCTGGACTACTGGGGACAGGGTACTCTCGTGACCGTGTC
ATCGGGCGGAGGAGGTTCCGGCGGTGGCGGCTCCGGCGGCGGAGGGTCGG
AGATCGTGATGACCCAGAGCCCTGGTACTCTGAGCCTTTCGCCGGGAGAA
AGGGCCACCCTGTCCTGCCGCGCTTCCCAATCCGTGTCCTCCGCGTACTT
GGCGTGGTACCAGCAGAAGCCGGGACAGCCCCCTCGGCTGCTGATCAGCG
GGGCCAGCACCCGGGCAACCGGAATCCCAGACAGATTCGGGGGTTCCGGC
AGCGGCACAGATTTCACCCTGACTATTTCGAGGTTGGAGCCCGAGGACTT
TGCGGTGTATTACTGTCAGCACTACGGGTCGTCCTTTAATGGCTCCAGCC
TGTTCACGTTCGGACAGGGGACCCGCCTGGAAATCAAG
BCMA_EBB-379EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1978-A4-aaISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVE
VHGSGSLDYWGQGTLVTVSS
BCMA_EBB-400EIVMTQSPGTLSLSPGERATLSCRASQSVSSAYLAWYQQKPGQPPRLLIS
C1978-A4-aaGASTRATGIPDRFGGSGSGTDFTLTISRLEPEDFAVYYCQHYGSSFNGSS
VLLFTFGQGTRLEIK
BCMA_EBB-C1978-G1
BCMA_EBB-338EVQLVETGGGLVQPGGSLRLSCAASGITFSRYPMSWVRQAPGKGLEWVSG
C1978-G1-aaISDSGVSTYYADSAKGRFTISRDNSKNTLFLQMSSLRDEDTAVYYCVTRA
ScFv domainGSEASDIWGQGTMVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGE
RATLSCRASQSVSNSLAWYQQKPGQAPRLLIYDASSRATGIPDRFSGSGS
GTDFTLTISRLEPEDFAIYYCQQFGTSSGLTFGGGTKLEIK
BCMA_EBB-359GAAGTGCAACTGGTGGAAACCGGTGGCGGCCTGGTGCAGCCTGGAGGATC
C1978-G1-ntATTGAGGCTGTCATGCGCGGCCAGCGGTATTACCTTCTCCCGGTACCCCA
ScFv domainTGTCCTGGGTCAGACAGGCCCCGGGGAAAGGGCTTGAATGGGTGTCCGGG
ATCTCGGACTCCGGTGTCAGCACTTACTACGCCGACTCCGCCAAGGGACG
CTTCACCATTTCCCGGGACAACTCGAAGAACACCCTGTTCCTCCAAATGA
GCTCCCTCCGGGACGAGGATACTGCAGTGTACTACTGCGTGACCCGCGCC
GGGTCCGAGGCGTCTGACATTTGGGGACAGGGCACTATGGTCACCGTGTC
GTCCGGCGGAGGGGGCTCGGGAGGCGGTGGCAGCGGAGGAGGAGGGTCCG
AGATCGTGCTGACCCAATCCCCGGCCACCCTCTCGCTGAGCCCTGGAGAA
AGGGCAACCTTGTCCTGTCGCGCGAGCCAGTCCGTGAGCAACTCCCTGGC
CTGGTACCAGCAGAAGCCCGGACAGGCTCCGAGACTTCTGATCTACGACG
CTTCGAGCCGGGCCACTGGAATCCCCGACCGCTTTTCGGGGTCCGGCTCA
GGAACCGATTTCACCCTGACAATCTCACGGCTGGAGCCAGAGGATTTCGC
CATCTATTACTGCCAGCAGTTCGGTACTTCCTCCGGCCTGACTTTCGGAG
GCGGCACGAAGCTCGAAATCAAG
BCMA_EBB-380EVQLVETGGGLVQPGGSLRLSCAASGITFSRYPMSWVRQAPGKGLEWVSG
C1978-G1-aaISDSGVSTYYADSAKGRFTISRDNSKNTLFLQMSSLRDEDTAVYYCVTRA
VHGSEASDIWGQGTMVTVSS
BCMA_EBB-401EIVLTQSPATLSLSPGERATLSCRASQSVSNSLAWYQQKPGQAPRLLIYD
C1978-G1-aaASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAIYYCQQFGTSSGLTFG
VLGGTKLEIK
BCMA_EBB-C1979-C1
BCMA_EBB-339QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMWVRQAPGKGLETAWSA
C1979-C1-aaISGSGGSTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAIYYCARAT
ScFv domainYKRELRYYYGMDVWGQGTMVTVSSGGGGSGGGGSGGGGSEIVMTQSPGTV
SLSPGERATLSCRASQSVSSSFLAWYQQKPGQAPRLLIYGASSRATGIPD
RFSGSGSGTDFTLTISRLEPEDSAVYYCQQYHSSPSWTFGQGTRLEIK
BCMA_EBB-360CAAGTGCAGCTCGTGGAATCGGGTGGCGGACTGGTGCAGCCGGGGGGCTC
C1979-C1-ntACTTAGACTGTCCTGCGCGGCCAGCGGATTCACTTTCTCCTCCTACGCCA
ScFv domainTGTCCTGGGTCAGACAGGCCCCTGGAAAGGGCCTGGAATGGGTGTCCGCA
ATCAGCGGCAGCGGCGGCTCGACCTATTACGCGGATTCAGGAAGGGCAG
ATTCACCATTTCCCGGGACAACGCCAAGAACTCCTTGTACCTTCAAATGA
ACTCCCTCCGCGCGGAAGATACCGCAATCTACTACTGCGCTCGGGCCACT
TACAAGAGGGAACTGCGCTACTACTACGGGATGGACGTCTGGGGCCAGGG
AACCATGGTCACCGTGTCCAGCGGAGGAGGAGGATCGGGAGGAGGCGGTA
GCGGGGGTGGAGGGTCGGAGATCGTGATGACCCAGTCCCCCGGCACTGTG
TCGCTGTCCCCCGGCGAACGGGCCACCCTGTCATGTCGGGCCAGCCAGTC
AGTGTCGTCAAGCTTCCTCGCCTGGTACCAGCAGAAACCGGGACAAGCTC
CCCGCCTGCTGATCTACGGAGCCAGCAGCCGGGCCACCGGTATTCCTGAC
CGGTTCTCCGGTTCGGGGTCCGGGACCGACTTTACTCTGACTATCTCTCG
CCTCGAGCCAGAGGACTCCGCCGTGTATTACTGCCAGCAGTACCACTCCT
CCCCGTCCTGGACGTTCGGACAGGGCACAAGGCTGGAGATTAAG
BCMA_EBB-381QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1979-C1-aaISGSGGSTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAIYYCARAT
VHYKRELRYYYGMDVWGQGTMVTVSS
BCMA_EBB-402EIVMTQSPGTVSLSPGERATLSCRASQSVSSSFLAWYQQKPGQAPRLLIY
C1979-C1-aaGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDSAVYYCQQYHSSPSWTF
VLGQGTRLEIK
BCMA_EBB-C1978-C7
BCMA_EBB-340EVQLVETGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1978-C7-aaISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNTLKAEDTAVYYCARAT
ScFv domainYKRELRYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPSTL
SLSPGESATLSCRASQSVSTTFLAWYQQKPGQAPRLLIYGSSNRATGIPD
RFSGSGSGTDFTLTIRRLEPEDFAVYYCQQYHSSPSWTFGQGTKVEIK
BCMA_EBB-361GAGGTGCAGCTTGTGGAAACCGGTGGCGGACTGGTGCAGCCCGGAGGAAG
C1978-C7-ntCCTCAGGCTGTCCTGCGCCGCGTCCGGCTTCACCTTCTCCTCGTACGCCA
ScFv domainTGTCCTGGGTCCGCCAGGCCCCCGGAAAGGGCCTGGAATGGGTGTCCGCC
ATCTCTGGAAGCGGAGGTTCCACGTACTACGCGGACAGCGTCAAGGGAAG
GTTCACAATCTCCCGCGATAATTCGAAGAACACTCTGTACCTTCAAATGA
ACACCCTGAAGGCCGAGGACACTGCTGTGTACTACTGCGCACGGGCCACC
TACAAGAGAGAGCTCCGGTACTACTACGGAATGGACGTCTGGGGCCAGGG
AACTACTGTGACCGTGTCCTCGGGAGGGGGTGGCTCCGGGGGGGGCGGCT
CCGGCGGAGGCGGTTCCGAGATTGTGCTGACCCAGTCACCTTCAACTCTG
TCGCTGTCCCCGGGAGAGAGCGCTACTCTGAGCTGCCGGGCCAGCCAGTC
CGTGTCCACCACCTTCCTCGCCTGGTATCAGCAGAAGCCGGGGCAGGCAC
CACGGCTCTTGATCTACGGGTCAAGCAACAGAGCGACCGGAATTCCTGAC
CGCTTCTCGGGGAGCGGTTCAGGCACCGACTTCACCCTGACTATCCGGCG
CCTGGAACCCGAAGATTTCGCCGTGTATTACTGTCAACAGTACCACTCCT
CGCCGTCCTGGACCTTTGGCCAAGGAACCAAAGTGGAAATCAAG
BCMA_EBB-382EVQLVETGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1978-C7-aaISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNTLKAEDTAVYYCARAT
VHYKRELRYYYGMDVWGQGTTVTVSS
BCMA_EBB-403EIVLTQSPSTLSLSPGESATLSCRASQSVSTTFLAWYQQKPGQAPRLLIY
C1978-C7-aaGSSNRATGIPDRFSGSGSGTDFTLTIRRLEPEDFAVYYCQQYHSSPSWTF
VLGQGTKVEIK
BCMA_EBB-C1978-D10
BCMA_EBB-341EVQLVETGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSG
C1978-D10-aaISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCARVG
ScFv domainKAVPDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIVMTQTPSSLSASVGDR
VTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
TDFTLTISSLQPEDFATYYCQQSYSTPYSFGQGTRLEIK
BCMA_EBB-362GAAGTGCAGCTCGTGGAAACTGGAGGTGGACTCGTGCAGCCTGGACGGTC
C1978-D10-ntGCTGCGGCTGAGCTGCGCTGCATCCGGCTTCACCTTCGACGATTATGCCA
ScFv domainTGCACTGGGTCAGACAGGCGCCAGGGAAGGGACTTGAGTGGGTGTCCGGT
ATCAGCTGGAATAGCGGCTCAATCGGATACGCGGACTCCGTGAAGGGAAG
GTTCACCATTTCCCGCGACAACGCCAAGAACTCCCTGTACTTGCAAATGA
ACAGCCTCCGGGATGAGGACACTGCCGTGTACTACTGCGCCCGCGTCGGA
AAAGCTGTGCCCGACGTCTGGGGCCAGGGAACCACTGTGACCGTGTCCAG
CGGCGGGGGTGGATCGGGCGGTGGAGGGTCCGGTGGAGGGGGCTCAGATA
TTGTGATGACCCAGACCCCCTCGTCCCTGTCCGCCTCGGTCGGCGACCGC
GTGACTATCACATGTAGAGCCTCGCAGAGCATCTCCAGCTACCTGAACTG
GTATCAGCAGAAGCCGGGGAAGGCCCCGAAGCTCCTGATCTACGCGGCAT
CATCACTGCAATCGGGAGTGCCGAGCCGGTTTTCCGGGTCCGGCTCCGGC
ACCGACTTCACGCTGACCATTTCTTCCCTGCAACCCGAGGACTTCGCCAC
TTACTACTGCCAGCAGTCCTACTCCACCCCTTACTCCTTCGGCCAAGGAA
CCAGGCTGGAAATCAAG
BCMA_EBB-383EVQLVETGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSG
C1978-D10-aaISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCARVG
VHKAVPDVWGQGTTVTVSS
BCMA_EBB-404DIVMTQTPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYA
C1978-D10-aaASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYSFGQ
VLGTRLEIK
BCMA_EBB-C1979-C12
BCMA_EBB-342EVQLVESGGGLVQPGRSLRLSCTASGFTFDDYAMHWVRQRPGKGLEWVAS
C1979-C12-aaINWKGNSLAYGDSVKGRFAISRDNAKNTVFLQMNSLRTEDTAVYYCASHQ
ScFv domainGVAYYNYAMDVWGRGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSL
SPGERATLSCRATQSIGSSFLAWYQQRPGQAPRLLIYGASQRATGIPDRF
SGRGSGTDFTLTISRVEPEDSAVYYCQHYESSPSWTFGQGTKVEIK
BCMA_EBB-363GAAGTGCAGCTCGTGGAGAGCGGGGGAGGATTGGTGCAGCCCGGAAGGTC
C1979-C12-ntCCTGCGGCTCTCCTGCACTGCGTCTGGCTTCACCTTCGACGACTACGCGA
ScFv domainTGCACTGGGTCAGACAGCGCCCGGGAAAGGGCCTGGAATGGGTCGCCTCA
ATCAACTGGAAGGGAAACTCCCTGGCCTATGGCGACAGCGTGAAGGGCCG
CTTCGCCATTTCGCGCGACAACGCCAAGAACACCGTGTTTCTGCAAATGA
ATTCCCTGCGGACCGAGGATACCGCTGTGTACTACTGCGCCAGCCACCAG
GGCGTGGCATACTATAACTACGCCATGGACGTGTGGGGAAGAGGGACGCT
CGTCACCGTGTCCTCCGGGGGCGGTGGATCGGGTGGAGGAGGAAGCGGTG
GCGGGGGCAGCGAAATCGTGCTGACTCAGAGCCCGGGAACTCTTTCACTG
TCCCCGGGAGAACGGGCCACTCTCTCGTGCCGGGCCACCCAGTCCATCGG
CTCCTCCTTCCTTGCCTGGTACCAGCAGAGGCCAGGACAGGCGCCCCGCC
TGCTGATCTACGGTGCTTCCCAACGCGCCACTGGCATTCCTGACCGGTTC
AGCGGCAGAGGGTCGGGAACCGATTTCACACTGACCATTTCCCGGGTGGA
GCCCGAAGATTCGGCAGTCTACTACTGTCAGCATTACGAGTCCTCCCCTT
CATGGACCTTCGGTCAAGGGACCAAAGTGGAGATCAAG
BCMA_EBB-384EVQLVESGGGLVQPGRSLRLSCTASGFTFDDYAMHWVRQRPGKGLEWVAS
C1979-C12-aaINWKGNSLAYGDSVKGRFAISRDNAKNTVFLQMNSLRTEDTAVYYCASHQ
VHGVAYYNYAMDVWGRGTLVTVSS
BCMA_EBB-405EIVLTQSPGTLSLSPGERATLSCRATQSIGSSFLAWYQQRPGQAPRLLIY
C1979-C12-aaGASQRATGIPDRFSGRGSGTDFTLTISRVEPEDSAVYYCQHYESSPSWTF
VLGQGTKVEIK
BCMA_EBB-C1980-G4
BCMA_EBB-343EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1980-G4-aaISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVV
ScFv domainRDGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGER
ATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGNGS
GTDFTLTISRLEPEDFAVYYCQQYGSPPRFTFGPGTKVDIK
BCMA_EBB-364GAGGTGCAGTTGGTCGAAAGCGGGGGCGGGCTTGTGCAGCCTGGCGGATC
C1980-G4-ntACTGCGGCTGTCCTGCGCGGCATCAGGCTTCACGTTTTCTTCCTACGCCA
ScFv domainTGTCCTGGGTGCGCCAGGCCCCTGGAAAGGGACTGGAATGGGTGTCCGCG
ATTTCGGGGTCCGGCGGGAGCACCTACTACGCCGATTCCGTGAAGGGCCG
CTTCACTATCTCGCGGGACAACTCCAAGAACACCCTCTACCTCCAAATGA
ATAGCCTGCGGGCCGAGGATACCGCCGTCTACTATTGCGCTAAGGTCGTG
CGCGACGGAATGGACGTGTGGGGACAGGGTACCACCGTGACAGTGTCCTC
GGGGGGAGGCGGTAGCGGCGGAGGAGGAAGCGGTGGTGGAGGTTCCGAGA
TTGTGCTGACTCAATCACCCGCGACCCTGAGCCTGTCCCCCGGCGAAAGG
GCCACTCTGTCCTGTCGGGCCAGCCAATCAGTCTCCTCCTCGTACCTGGC
CTGGTACCAGCAGAAGCCAGGACAGGCTCCGAGACTCCTTATCTATGGCG
CATCCTCCCGCGCCACCGGAATCCCGGATAGGTTCTCGGGAAACGGATCG
GGGACCGACTTCACTCTCACCATCTCCCGGCTGGAACCGGAGGACTTCGC
CGTGTACTACTGCCAGCAGTACGGCAGCCCGCCTAGATTCACTTTCGGCC
CCGGCACCAAAGTGGACATCAAG
BCMA_EBB-385EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1980-G4-aaISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVV
VHRDGMDVWGQGTTVTVSS
BCMA_EBB-406EIVLTQSPATLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIY
C1980-G4-aaGASSRATGIPDRFSGNGSGTDFTLTISRLEPEDFAVYYCQQYGSPPRFTF
VLGPGTKVDIK
BCMA_EBB-C1980-D2
BCMA_EBB-344EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1980-D2-aaISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKIP
ScFv domainQTGTFDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGE
RAILSCRASQSVSSSYLAWYQQRPGQAPRLLIYGASSRATGIPDRFSGSG
SGTDFTLTISRLEPEDFAVYYCQHYGSSPSWTFGQGTRLEIK
BCMA_EBB-365GAAGTGCAGCTGCTGGAGTCCGGCGGTGGATTGGTGCAACCGGGGGGATC
C1980-D2-ntGCTCAGACTGTCCTGTGCGGCGTCAGGCTTCACCTTCTCGAGCTACGCCA
ScFv domainTGTCATGGGTCAGACAGGCCCCTGGAAAGGGTCTGGAATGGGTGTCCGCC
ATTTCCGGGAGCGGGGGATCTACATACTACGCCGATAGCGTGAAGGGCCG
CTTCACCATTTCCCGGGACAACTCCAAGAACACTCTCTATCTGCAAATGA
ACTCCCTCCGCGCTGAGGACACTGCCGTGTACTACTGCGCCAAAATCCCT
CAGACCGGCACCTTCGACTACTGGGGACAGGGGACTCTGGTCACCGTCAG
CAGCGGTGGCGGAGGTTCGGGGGGAGGAGGAAGCGGCGGCGGAGGGTCCG
AGATTGTGCTGACCCAGTCACCCGGCACTTTGTCCCTGTCGCCTGGAGAA
AGGGCCACCCTTTCCTGCCGGGCATCCCAATCCGTGTCCTCCTCGTACCT
GGCCTGGTACCAGCAGAGGCCCGGACAGGCCCCACGGCTTCTGATCTACG
GAGCAAGCAGCCGCGCGACCGGTATCCCGGACCGGTTTTCGGGCTCGGGC
TCAGGAACTGACTTCACCCTCACCATCTCCCGCCTGGAACCCGAAGATTT
CGCTGTGTATTACTGCCAGCACTACGGCAGCTCCCCGTCCTGGACGTTCG
GCCAGGGAACTCGGCTGGAGATCAAG
BCMA_EBB-386EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1980-D2-aaISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKIP
VHQTGTFDYWGQGTLVTVSS
BCMA_EBB-407EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQRPGQAPRLLIY
C1980-D2-aaGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGSSPSWTF
VLGQGTRLEIK
BCMA_EBB-C1978-A10
BCMA_EBB-345EVQLVETGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1978-A10-aaISGSGGSTYYADSVKGRFTMSRENDKNSVFLQMNSLRVEDTGVYYCARAN
ScFv domainYKRELRYYYGMDVWGQGTMVTVSSGGGGSGGGGSGGGGSEIVMTQSPGTL
SLSPGESATLSCRASQRVASNYLAWYQHKPGQAPSLLISGASSRATGVPD
RFSGSGSGTDFTLAISRLEPEDSAVYYCQHYDSSPSWTFGQGTKVEIK
BCMA_EBB-366GAAGTGCAACTGGTGGAAACCGGTGGAGGACTCGTGCAGCCTGGCGGCAG
C1978-A10-ntCCTCCGGCTGAGCTGCGCCGCTTCGGGATTCACCTTTTCCTCCTACGCGA
ScFv domainTGTCTTGGGTCAGACAGGCCCCCGGAAAGGGGCTGGAATGGGTGTCAGCC
ATCTCCGGCTCCGGCGGATCAACGTACTACGCCGACTCCGTGAAAGGCCG
GTTCACCATGTCGCGCGAGAATGACAAGAACTCCGTGTTCCTGCAAATGA
ACTCCCTGAGGGTGGAGGACACCGGAGTGTACTATTGTGCGCGCGCCAAC
TACAAGAGAGAGCTGCGGTACTACTACGGAATGGACGTCTGGGGACAGGG
AACTATGGTGACCGTGTCATCCGGTGGAGGGGGAAGCGGCGGTGGAGGCA
GCGGGGGCGGGGGTTCAGAAATTGTCATGACCCAGTCCCCGGGAACTCTT
TCCCTCTCCCCCGGGGAATCCGCGACTTTGTCCTGCCGGGCCAGCCAGCG
CGTGGCCTCGAACTACCTCGCATGGTACCAGCATAAGCCAGGCCAAGCCC
CTTCCCTGCTGATTTCCGGGGCTAGCAGCCGCGCCACTGGCGTGCCGGAT
AGGTTCTCGGGAAGCGGCTCGGGTACCGATTTCACCCTGGCAATCTCGCG
GCTGGAACCGGAGGATTCGGCCGTGTACTACTGCCAGCACTATGACTCAT
CCCCCTCCTGGACATTCGGACAGGGCACCAAGGTCGAGATCAAG
BCMA_EBB-387EVQLVETGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1978-A10-aaISGSGGSTYYADSVKGRFTMSRENDKNSVFLQMNSLRVEDTGVYYCARAN
VHYKRELRYYYGMDVWGQGTMVTVSS
BCMA_EBB-408EIVMTQSPGTLSLSPGESAILSCRASQRVASNYLAWYQHKPGQAPSLLIS
C1978-A10-aaGASSRATGVPDRFSGSGSGTDFTLAISRLEPEDSAVYYCQHYDSSPSWTF
VLGQGTKVEIK
BCMA_EBB-C1978-D4
BCMA_EBB-346EVQLLETGGGLVQPGGSLRLSCAASGFSFSSYAMSWVRQAPGKGLEWVSA
C1978-D4-aaISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKAL
ScFv domainVGATGAFDIWGQGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSP
GERATLSCRASQSLSSNFLAWYQQKPGQAPGLLIYGASNWATGTPDRFSG
SGSGTDFTLTITRLEPEDFAVYYCQYYGTSPMYTFGQGTKVEIK
BCMA_EBB-367GAAGTGCAGCTGCTCGAAACCGGTGGAGGGCTGGTGCAGCCAGGGGGCTC
C1978-D4-ntCCTGAGGCTTTCATGCGCCGCTAGCGGATTCTCCTTCTCCTCTTACGCCA
ScFv domainTGTCGTGGGTCCGCCAAGCCCCTGGAAAAGGCCTGGAATGGGTGTCCGCG
ATTTCCGGGAGCGGAGGTTCGACCTATTACGCCGACTCCGTGAAGGGCCG
CTTTACCATCTCCCGGGATAACTCCAAGAACACTCTGTACCTCCAAATGA
ACTCGCTGAGAGCCGAGGACACCGCCGTGTATTACTGCGCGAAGGCGCTG
GTCGGCGCGACTGGGGCATTCGACATCTGGGGACAGGGAACTCTTGTGAC
CGTGTCGAGCGGAGGCGGCGGCTCCGGCGGAGGAGGGAGCGGGGGCGGTG
GTTCCGAAATCGTGTTGACTCAGTCCCCGGGAACCCTGAGCTTGTCACCC
GGGGAGCGGGCCACTCTCTCCTGTCGCGCCTCCCAATCGCTCTCATCCAA
TTTCCTGGCCTGGTACCAGCAGAAGCCCGGACAGGCCCCGGGCCTGCTCA
TCTACGGCGCTTCAAACTGGGCAACGGGAACCCCTGATCGGTTCAGCGGA
AGCGGATCGGGTACTGACTTTACCCTGACCATCACCAGACTGGAACCGGA
GGACTTCGCCGTGTACTACTGCCAGTACTACGGCACCTCCCCCATGTACA
CATTCGGACAGGGTACCAAGGTCGAGATTAAG
BCMA_EBB-388EVQLLETGGGLVQPGGSLRLSCAASGFSFSSYAMSWVRQAPGKGLEWVSA
C1978-D4-aaISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKAL
VHVGATGAFDIWGQGTLVTVSS
BCMA_EBB-409EIVLTQSPGTLSLSPGERATLSCRASQSLSSNFLAWYQQKPGQAPGLLIY
C1978-D4-aaGASNWATGTPDRFSGSGSGTDFTLTITRLEPEDFAVYYCQYYGTSPMYTF
VLGQGTKVEIK
BCMA_EBB-C1980-A2
BCMA_EBB-347EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1980-A2-aaISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCVLWF
ScFv domainGEGFDPWGQGTLVTVSSGGGGSGGGGSGGGGSDIVLTQSPLSLPVTPGEP
ASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFS
GSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGGGTKVDIK
BCMA_EBB-368GAAGTGCAGCTGCTTGAGAGCGGTGGAGGTCTGGTGCAGCCCGGGGGATC
C1980-A2-ntACTGCGCCTGTCCTGTGCCGCGTCCGGTTTCACTTTCTCCTCGTACGCCA
ScFv domainTGTCGTGGGTCAGACAGGCACCGGGAAAGGGACTGGAATGGGTGTCAGCC
ATTTCGGGTTCGGGGGGCAGCACCTACTACGCTGACTCCGTGAAGGGCCG
GTTCACCATTTCCCGCGACAACTCCAAGAACACCTTGTACCTCCAAATGA
ACTCCCTGCGGGCCGAAGATACCGCCGTGTATTACTGCGTGCTGTGGTTC
GGAGAGGGATTCGACCCGTGGGGACAAGGAACACTCGTGACTGTGTCATC
CGGCGGAGGCGGCAGCGGTGGCGGCGGTTCCGGCGGCGGCGGATCTGACA
TCGTGTTGACCCAGTCCCCTCTGAGCCTGCCGGTCACTCCTGGCGAACCA
GCCAGCATCTCCTGCCGGTCGAGCCAGTCCCTCCTGCACTCCAATGGGTA
CAACTACCTCGATTGGTATCTGCAAAAGCCGGGCCAGAGCCCCCAGCTGC
TGATCTACCTTGGGTCAAACCGCGCTTCCGGGGTGCCTGATAGATTCTCC
GGGTCCGGGAGCGGAACCGACTTTACCCTGAAAATCTCGAGGGTGGAGGC
CGAGGACGTCGGAGTGTACTACTGCATGCAGGCGCTCCAGACTCCCCTGA
CCTTCGGAGGAGGAACGAAGGTCGACATCAAGA
BCMA_EBB-389EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1980-A2-aaISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCVLWF
VHGEGFDPWGQGTLVTVSS
BCMA_EBB-410DIVLTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQ
C1980-A2-aaLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTP
VLLTFGGGTKVDIK
BCMA_EBB-C1981-C3
BCMA_EBB-348QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1981-C3-aaISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVG
ScFv domainYDSSGYYRDYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPG
TLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGTSSRATGI
SDRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGNSPPKFTFGPGTKLEI
K
BCMA_EBB-369CAAGTGCAGCTCGTGGAGTCAGGCGGAGGACTGGTGCAGCCCGGGGGCTC
C1981-C3-ntCCTGAGACTTTCCTGCGCGGCATCGGGTTTTACCTTCTCCTCCTATGCTA
ScFv domainTGTCCTGGGTGCGCCAGGCCCCGGGAAAGGGACTGGAATGGGTGTCCGCA
ATCAGCGGTAGCGGGGGCTCAACATACTACGCCGACTCCGTCAAGGGTCG
CTTCACTATTTCCCGGGACAACTCCAAGAATACCCTGTACCTCCAAATGA
ACAGCCTCAGGGCCGAGGATACTGCCGTGTACTACTGCGCCAAAGTCGGA
TACGATAGCTCCGGTTACTACCGGGACTACTACGGAATGGACGTGTGGGG
ACAGGGCACCACCGTGACCGTGTCAAGCGGCGGAGGCGGTTCAGGAGGGG
GAGGCTCCGGCGGTGGAGGGTCCGAAATCGTCCTGACTCAGTCGCCTGGC
ACTCTGTCGTTGTCCCCGGGGGAGCGCGCTACCCTGTCGTGTCGGGCGTC
GCAGTCCGTGTCGAGCTCCTACCTCGCGTGGTACCAGCAGAAGCCCGGAC
AGGCCCCTAGACTTCTGATCTACGGCACTTCTTCACGCGCCACCGGGATC
AGCGACAGGTTCAGCGGCTCCGGCTCCGGGACCGACTTCACCCTGACCAT
TAGCCGGCTGGAGCCTGAAGATTTCGCCGTGTATTACTGCCAACACTACG
GAAACTCGCCGCCAAAGTTCACGTTCGGACCCGGAACCAAGCTGGAAATC
APG
BCMA_EBB-390QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1981-C3-aaISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVG
VHYDSSGYYRDYYGMDVWGQGTTVTVSS
BCMA_EBB-411EIVLIQSPGILSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIY
C1981-C3-aaGTSSRATGISDRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGNSPPKFT
VLFGPGTKLEIK
BCMA_EBB-C1978-G4
BCMA_EBB-349EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1978-G4-aaISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKMG
ScFv domainWSSGYLGAFDIWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSL
SPGERATLSCRASQSVASSFLAWYQQKPGQAPRLLIYGASGRATGIPDRF
SGSGSGTDFTLTISRLEPEDFAVYYCQHYGGSPRLTFGGGTKVDIK
BCMA_EBB-370GAAGTCCAACTGGTGGAGTCCGGGGGAGGGCTCGTGCAGCCCGGAGGCAG
C1978-G4-ntCCTTCGGCTGTCGTGCGCCGCCTCCGGGTTCACGTTCTCATCCTACGCGA
ScFv domainTGTCGTGGGTCAGACAGGCACCAGGAAAGGGACTGGAATGGGTGTCCGCC
ATTAGCGGCTCCGGCGGTAGCACCTACTATGCCGACTCAGTGAAGGGAAG
GTTCACTATCTCCCGCGACAACAGCAAGAACACCCTGTACCTCCAAATGA
ACTCTCTGCGGGCCGAGGATACCGCGGTGTACTATTGCGCCAAGATGGGT
TGGTCCAGCGGATACTTGGGAGCCTTCGACATTTGGGGACAGGGCACTAC
TGTGACCGTGTCCTCCGGGGGTGGCGGATCGGGAGGCGGCGGCTCGGGTG
GAGGGGGTTCCGAAATCGTGTTGACCCAGTCACCGGGAACCCTCTCGCTG
TCCCCGGGAGAACGGGCTACACTGTCATGTAGAGCGTCCCAGTCCGTGGC
TTCCTCGTTCCTGGCCTGGTACCAGCAGAAGCCGGGACAGGCACCCCGCC
TGCTCATCTACGGAGCCAGCGGCCGGGCGACCGGCATCCCTGACCGCTTC
TCCGGTTCCGGCTCGGGCACCGACTTTACTCTGACCATTAGCAGGCTTGA
GCCCGAGGATTTTGCCGTGTACTACTGCCAACACTACGGGGGGAGCCCTC
GCCTGACCTTCGGAGGCGGAACTAAGGTCGATATCAAAA
BCMA_EBB-391EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA
C1978-G4-aaISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKMG
VHWSSGYLGAFDIWGQGTTVTVSS
BCMA_EBB-412EIVLTQSPGTLSLSPGERATLSCRASQSVASSFLAWYQQKPGQAPRLLIY
C1978-G4-aaGASGRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGGSPRLTF
VLGGGTKVDIK
TABLE 9 — Additional exemplary BCMA binding domain sequences SEQ ID
NameSequenceNO:
A7D12.2QIQLVQSGPDLKKPGETVKLSCKASGYTFTNFGMNWVKQAPGKGFKWMAWINTY455
VHTGESYFADDFKGRFAFSVETSATTAYLQINNLKTEDTATYFCARGEIYYGYDGG
FAYWGQGTLVTVSA
A7D12.2DVVMTQSHRFMSTSVGDRVSITCRASQDVNTAVSWYQQKPGQSPKLLIFSASYR459
VLYTGVPDRFTGSGSGADFTLTISSVQAEDLAVYYCQQHYSTPWTFGGGTKLDIK
A7D12.2QIQLVQSGPDLKKPGETVKLSCKASGYTFTNFGMNWVKQAPGKGFKWMAWINTY463
scFvTGESYFADDFKGRFAFSVETSATTAYLQINNLKTEDTATYFCARGEIYYGYDGG
domainFAYWGQGTLVTVSAGGGGSGGGGSGGGGSDVVMTQSHRFMSTSVGDRVSITCRA
SQDVNTAVSWYQQKPGQSPKLLIFSASYRYTGVPDRFTGSGSGADFTLTISSVQ
AEDLAVYYCQQHYSTPWTFGGGTKLDIK
C11D5.3QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTE456
VHTREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWG
QGTSVTVSS
C11D5.3DIVLTQSPASLAMSLGKRATISCRASESVSVIGAHLIHWYQQKPGQPPKLLIYL460
VLASNLETGVPARFSGSGSGTDFTLTIDPVEEDDVAIYSCLQSRIFPRTFGGGTKL
EIK
C11D5.3QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTE464
scFvTREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWG
domainQGTSVTVSSGGGGSGGGGSGGGGSQIQLVQSGPELKKPGETVKISCKASGYTFT
DYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQIN
NLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS
C12A3.2QIQLVQSGPELKKPGETVKISCKASGYTFRHYSMNWVKQAPGKGLKWMGRINTE457
VHSGVPIYADDFKGRFAFSVETSASTAYLVINNLKDEDTASYFCSNDYLYSLDFWG
QGTALTVSS
C12A3.2DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIYWYQQKPGQPPTLLIQL461
VLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKL
EIK
C12A3.2QIQLVQSGPELKKPGETVKISCKASGYTFRHYSMNWVKQAPGKGLKWMGRINTE465
scFvSGVPIYADDFKGRFAFSVETSASTAYLVINNLKDEDTASYFCSNDYLYSLDFWG
domainQGTALTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVT
ILGSHLIYWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEE
DDVAVYYCLQSRTIPRTFGGGTKLEIK
C13F12.1QIQLVQSGPELKKPGETVKISCKASGYTFTHYSMNWVKQAPGKGLKWMGRINTE458
VHTGEPLYADDFKGRFAFSLETSASTAYLVINNLKNEDTATFFCSNDYLYSCDYWG
QGTTLTVSS
C13F12.1DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIYWYQQKPGQPPTLLIQL462
VLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKL
EIK
C13F12.1QIQLVQSGPELKKPGETVKISCKASGYTFTHYSMNWVKQAPGKGLKWMGRINTE466
scFvTGEPLYADDFKGRFAFSLETSASTAYLVINNLKNEDTATFFCSNDYLYSCDYWG
domainQGTTLTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVT
ILGSHLIYWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEE
DDVAVYYCLQSRTIPRTFGGGTKLEIK
TABLE 10 — Heavy Chain Variable Domain CDRs from the sequences above according to the Kabat numbering scheme (Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD)
CandidateHCDR1IDHCDR2IDHCDR3ID
139109NHGMS594GIVYSGSTYYAAS634HGGESDV674
VKG
139103NYAMS584GISRSGENTYYAD624SPAHYYGGMDV664
SVKG
139105DYAMH585GISWNSGSIGYAD625HSFLAY665
SVKG
139111NHGMS586GIVYSGSTYYAAS626HGGESDV666
VKG
139100NFGIN587WINPKNNNTNYA627GPYYYQSYMDV667
QKFQG
139101SDAMT588VISGSGGTTYYA628LDSSGYYYARGPR668
DSVKGY
139102NYGIT589WISAYNGNTNYA629GPYYYYMDV669
QKFQG
139104NHGMS590GIVYSGSTYYAAS630HGGESDV670
VKG
139106NHGMS591GIVYSGSTYYAAS631HGGESDV671
VKG
139107NHGMS592GIVYSGSTYYAAS632HGGESDV672
VKG
139108DYYMS593YISSSGSTIYYADS633ESGDGMDV673
VKG
139110DYYMS595YISSSGNTIYYAD635STMVREDY675
SVKG
139112NHGMS596GIVYSGSTYYAAS636HGGESDV676
VKG
139113NHGMS597GIVYSGSTYYAAS637HGGESDV677
VKG
139114NHGMS598GIVYSGSTYYAAS638HGGESDV678
VKG
149362SSYYYW599SIYYSGSAYYNPS639HWQEWPDAFDI679
GLKS
149363TSGMCV600RIDWDEDKFYST640SGAGGTSATAFDI680
SSLKT
149364SYSMN601SISSSSSYIYYADS641TIAAVYAFDI681
VKG
149365DYYMS602YISSSGSTIYYADS642DLRGAFDI682
VKG
149366SHYIH603MNSGGVTAYS643EGSGSGWYFDF683
QTLQG
149367SGGYY604YIYYSGSTYYNPS644AGIAARLRGAFDI684
WSLKS
149368SYAIS605GIIPIFGTANYAQ645RGGYQLLRWDVG685
KFQGLLRSAFDI
149369SNSAAW606RTYYRSKWYSFY646SSPEGLFLYWFDP686
NAISLKS
BCMA_EBSYAMS607AISGSGGSTYYAD647VEGSGSLDY687
B-C1978-SVKG
A4
BCMA_EBRYPMS608GISDSGVSTYYAD648RAGSEASDI688
B-C1978-SAKG
G1
BCMA_EBSYAMS609AISGSGGSTYYAD649ATYKRELRYYYG689
B-C1979-SVKGMDV
Cl
BCMA_EBSYAMS610AISGSGGSTYYAD650ATYKRELRYYYG690
B-C1978-SVKGMDV
C7
BCMA_EBDYAMH611GISWNSGSIGYAD651VGKAVPDV691
B-C1978-SVKG
D10
BCMA_EBDYAMH612SINWKGNSLAYG652HQGVAYYNYAMD692
B-C1979-DSVKGV
C12
BCMA_EBSYAMS613AISGSGGSTYYAD653VVRDGMDV693
B-C1980-SVKG
G4
BCMA_EBSYAMS614AISGSGGSTYYAD654IPQTGTFDY694
B-C1980-SVKG
D2
BCMA_EBSYAMS615AISGSGGSTYYAD655ANYKRELRYYYG695
B-C1978-SVKGMDV
A10
BCMA_EBSYAMS616AISGSGGSTYYAD656ALVGATGAFDI696
B-C1978-SVKG
D4
BCMA_EBSYAMS617AISGSGGSTYYAD657WFGEGFDP697
B-C1980-SVKG
A2
BCMA_EBSYAMS618AISGSGGSTYYAD658VGYDSSGYYRDY698
B-C1981-SVKGYGMDV
C3
BCMA_EBSYAMS619AISGSGGSTYYAD659MGWSSGYLGAFDI699
B-C1978-SVKG
G4
A7D12.2NFGMN620WINTYTGESYFA660GEIYYGYDGGFAY700
DDFKG
C11D5.3DYSIN621WINTETREPAYA661DYSYAMDY701
YDFRG
C12A3.2HYSMN622RINTESGVPIYAD662DYLYSLDF702
DFKG
C13F12.1HYSMN623RINTETGEPLYAD663DYLYSCDY703
DFKG
TABLE 11 — Light Chain Variable Domain CDRs from the sequences above according to the Kabat numbering scheme (Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD)
CandidateLCDR1IDLCDR2IDLCDR3ID
139109RASQSISSYLN714AASSLQS754QQSYSTPYT794
139103RASQSISSSFLA704GASRRAT744QQYHSSPSWT784
139105RSSQSLLHSNGYNY705LGSNRAS745MQALQTPYT785
LD
139111KSSQSLLRNDGKTP706EVSNRFS746MQNIQFPS786
LY
139100RSSQSLLHSNGYNY707LGSKRAS747MQALQTPYT787
LN
139101RASQSISSYLN708GASTLAS748QQSYKRAS788
139102RSSQSLLYSNGYNY709LGSNRAS749MQGRQFPYS789
VD
139104RASQSVSSNLA710GASTRAS750QQYGSSLT790
139106RASQSVSSKLA711GASIRAT751QQYGSSSWT791
139107RASQSVGSTNLA712DASNRAT752QQYGSSPPWT792
139108RASQSISSYLN713AASSLQS753QQSYTLA793
139110KSSESLVHNSGKTY715EVSNRDS755MQGTHWPGT795
LN
139112QASEDINKFLN716DASTLQT756QQYESLPLT796
139113RASQSVGSNLA717GASTRAT757QQYNDWLPVT797
139114RASQSIGSSSLA718GASSRAS758QQYAGSPPFT798
149362KASQDIDDAMN719SATSPVP759LQHDNFPLT799
149363RASQDIYNNLA720AANKSQS760QHYYRFPYS800
149364RSSQSLLHSNGYNY721LGSNRAS761MQALQTPYT801
LD
149365GGNNIGTKSVH722DDSVRPS762QVWDSDSEHV802
V
149366SGDGLSKKYVS723RDKERPS763QAWDDTTVV803
149367RASQGIRNWLA724AASNLQS764QKYNSAPFT804
149368GGNNIGSKSVH725GKNNRPS765SSRDSSGDHLR805
V
149369QGDSLGNYYAT726GTNNRPS766NSRDSSGHHLL806
BCMA_ERASQSVSSAYLA727GASTRAT767QHYGSSFNGSS807
BB-LFT
C1978-A4
BCMA_ERASQSVSNSLA728DASSRAT768QQFGTSSGLT808
BB-
C1978-G1
BCMA_ERASQSVSSSFLA729GASSRAT769QQYHSSPSWT809
BB-
C1979-C1
BCMA_ERASQSVSTTFLA730GSSNRAT770QQYHSSPSWT810
BB-
C1978-C7
BCMA_ERASQSISSYLN731AASSLQS771QQSYSTPYS811
BB-
C1978-
D10
BCMA_ERATQSIGSSFLA732GASQRAT772QHYESSPSWT812
BB-
C1979-
C12
BCMA_ERASQSVSSSYLA733GASSRAT773QQYGSPPRFT813
BB-
C1980-G4
BCMA_ERASQSVSSSYLA734GASSRAT774QHYGSSPSWT814
BB-
C1980-D2
BCMA_ERASQRVASNYLA735GASSRAT775QHYDSSPSWT815
BB-
C1978-
A10
BCMA_ERASQSLSSNFLA736GASNWA776QYYGTSPMYT816
BB-T
C1978-D4
BCMA_ERSSQSLLHSNGYNY737LGSNRAS777MQALQTPLT817
BB-LD
C1980-A2
BCMA_ERASQSVSSSYLA738GTSSRAT778QHYGNSPPKFT818
BB-
C1981-C3
BCMA_ERASQSVASSFLA739GASGRAT779QHYGGSPRLT819
BB-
C1978-G4
A7D12.2RASQDVNTAVS740SASYRYT780QQHYSTPWT820
Cl1D5.3RASESVSVIGAHLI741LASNLET781LQSRIFPRT821
H
C12A3.2RASESVTILGSHLIY742LASNVQT782LQSRTIPRT822
C13F12.1RASESVTILGSHLIY743LASNVQT783LQSRTIPRT823
TABLE 12 — Exemplary CD19 CAR molecules SEQ ID
AntigenNameAmino Acid SequenceNO:
CD19CTL019MALPVTALLLPLALLLHAARPDIQMTQTTSSLSASLGDRVTISCRASQ185
DISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTI
SNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSGGGGSE
VKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLG
VIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAK
HYYYGGSYAMDYWGQGTSVIVSSTTTPAPRPPTPAPTIASQPLSLRPE
ACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGR
KKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADA
PAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGL
YNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHM
QALPPR
CD19CAR 1MALPVTALLLPLALLLHAARPEIVMTQSPATLSLSPGERATLSCRASQ186
DISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTI
SSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQ
VQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIG
VIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAK
HYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPE
ACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGR
KKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADA
PAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGL
YNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHM
QALPPR
CD19CAR 2MALPVTALLLPLALLLHAARPEIVMTQSPATLSLSPGERATLSCRASQ187
DISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTI
SSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQ
VQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIG
VIWGSETTYYQSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAK
HYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPE
ACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGR
KKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADA
PAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGL
YNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHM
QALPPR
CD19CAR 3MALPVTALLLPLALLLHAARPQVQLQESGPGLVKPSETLSLTCTVSGV188
SLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSK
NQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSGGG
GSGGGGSGGGGSEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWY
QQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFA
VYFCQQGNTLPYTFGQGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPE
ACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGR
KKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADA
PAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGL
YNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHM
QALPPR
CD19CAR 4MALPVTALLLPLALLLHAARPQVQLQESGPGLVKPSETLSLTCTVSGV189
SLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYQSSLKSRVTISKDNSK
NQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSGGG
GSGGGGSGGGGSEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWY
QQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFA
VYFCQQGNTLPYTFGQGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPE
ACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGR
KKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADA
PAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGL
YNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHM
QALPR
CD19CAR 5MALPVTALLLPLALLLHAARPEIVMTQSPATLSLSPGERATLSCRASQ190
DISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTI
SSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSG
GGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKG
LEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAV
YYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPL
SLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLY
CKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFS
RSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKN
PQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY
DALHMQALPPR
CD19CAR 6MALPVTALLLPLALLLHAARPEIVMTQSPATLSLSPGERATLSCRASQ191
DISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTI
SSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSG
GGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKG
LEWIGVIWGSETTYYQSSLKSRVTISKDNSKNQVSLKLSSVTAADTAV
YYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPL
SLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLY
CKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFS
RSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKN
PQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY
DALHMQALPPR
CD19CAR 7MALPVTALLLPLALLLHAARPQVQLQESGPGLVKPSETLSLTCTVSGV192
SLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSK
NQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSGGG
GSGGGGSGGGGSGGGGSEIVMTQSPATLSLSPGERATLSCRASQDISK
YLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQ
PEDFAVYFCQQGNTLPYTFGQGTKLEIKTTTPAPRPPTPAPTIASQPL
SLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLY
CKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFS
RSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKN
PQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY
DALHMQALPPR
CD19CAR 8MALPVTALLLPLALLLHAARPQVQLQESGPGLVKPSETLSLTCTVSGV193
SLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYQSSLKSRVTISKDNSK
NQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSGGG
GSGGGGSGGGGSGGGGSEIVMTQSPAILSLSPGERATLSCRASQDISK
YLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQ
PEDFAVYFCQQGNTLPYTFGQGTKLEIKTTTPAPRPPTPAPTIASQPL
SLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLY
CKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFS
RSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKN
PQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY
DALHMQALPPR
CD19CAR 9MALPVTALLLPLALLLHAARPEIVMTQSPAILSLSPGERATLSCRASQ194
DISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTI
SSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSG
GGGSQVQLQESGPGLVKPSETLSLICTVSGVSLPDYGVSWIRQPPGKG
LEWIGVIWGSETTYYNSSLKSRVTISKDNSKNQVSLKLSSVTAADTAV
YYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPL
SLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLY
CKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFS
RSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKN
PQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY
DALHMQALPPR
CD19CAR 10MALPVTALLLPLALLLHAARPEIVMTQSPATLSLSPGERATLSCRASQ195
DISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTI
SSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSG
GGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKG
LEWIGVIWGSETTYYNSSLKSRVTISKDNSKNQVSLKLSSVTAADTAV
YYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPL
SLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLY
CKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFS
RSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKN
PQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY
DALHMQALPPR
CD19CAR 11MALPVTALLLPLALLLHAARPQVQLQESGPGLVKPSETLSLTCTVSGV196
SLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYNSSLKSRVTISKDNSK
NQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSGGG
GSGGGGSGGGGSGGGGSEIVMTQSPATLSLSPGERATLSCRASQDISK
YLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQ
PEDFAVYFCQQGNTLPYTFGQGTKLEIKTTTPAPRPPTPAPTIASQPL
SLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLY
CKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFS
RSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKN
PQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY
DALHMQALPPR
CD19CAR 12MALPVTALLLPLALLLHAARPEIVMTQSPATLSLSPGERATLSCRASQ197
DISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTI
SSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQ
VQLQESGPGLVKPSETLSLICTVSGVSLPDYGVSWIRQPPGKGLEWIG
VIWGSETTYYNSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAK
HYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPE
ACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGR
KKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADA
PAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGL
YNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHM
QALPPR
TABLE 13 — Exemplary BCMA CAR molecules. Sequences are provided with a leader sequence. SEQ
Name/ID
DescriptionNO:Sequence
139109
139109-aa859MALPVTALLLPLALLLHAARPEVQLVESGGGLVQPGGSLRLSCAVSGFALS
Full CARNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQ
MNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGS
DIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAA
SSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGT
KVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDI
YIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGC
SCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDK
RRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDG
LYQGLSTATKDTYDALHMQALPPR
139109-nt874ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCGAAGTGCAATTGGTGGAATCAGGGGGAGGACTTGTGCAG
CCTGGAGGATCGCTGAGACTGTCATGTGCCGTGTCCGGCTTTGCCCTGTCC
AACCACGGGATGTCCTGGGTCCGCCGCGCGCCTGGAAAGGGCCTCGAATGG
GTGTCGGGTATTGTGTACAGCGGTAGCACCTACTATGCCGCATCCGTGAAG
GGGAGATTCACCATCAGCCGGGACAACTCCAGGAACACTCTGTACCTCCAA
ATGAATTCGCTGAGGCCAGAGGACACTGCCATCTACTACTGCTCCGCGCAT
GGCGGAGAGTCCGACGTCTGGGGACAGGGGACCACCGTGACCGTGTCTAGC
GCGTCCGGCGGAGGCGGCAGCGGGGGTCGGGCATCAGGGGGCGGCGGATCG
GACATCCAGCTCACCCAGTCCCCGAGCTCGCTGTCCGCCTCCGTGGGAGAT
CGGGTCACCATCACGTGCCGCGCCAGCCAGTCGATTTCCTCCTACCTGAAC
TGGTACCAACAGAAGCCCGGAAAAGCCCCGAAGCTTCTCATCTACGCCGCC
TCGAGCCTGCAGTCAGGAGTGCCCTCACGGTTCTCCGGCTCCGGTTCCGGT
ACTGATTTCACCCTGACCATTTCCTCCCTGCAACCGGAGGACTTCGCTACT
TACTACTGCCAGCAGTCGTACTCCACCCCCTACACTTTCGGACAAGGCACC
AAGGTCGAAATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCT
CCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCC
GCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTCGCCTGCGATATC
TACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTC
GTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTT
AAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGT
TCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGCGTGAAA
TTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTC
TACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAG
CGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCC
CAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTAT
AGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAAGGCCACGACGGA
CTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCAC
ATGCAGGCCCTGCCGCCTCGG
139103
139103-aa849MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGRSLRLSCAASGFTFS
Full CARNYAMSWVRQAPGKGLGWVSGISRSGENTYYADSVKGRFTISRDNSKNTLYL
QMNSLRDEDTAVYYCARSPAHYYGGMDVWGQGTTVTVSSASGGGGSGGRAS
GGGGSDIVLTQSPGTLSLSPGERATLSCRASQSISSSFLAWYQQKPGQAPR
LLIYGASRRATGIPDRFSGSGSGTDFTLTISRLEPEDSAVYYCQQYHSSPS
WTFGQGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRG
LDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQT
TQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRRE
EYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR
RGKGHDGLYQGLSTATKDTYDALHMQALPPR
139103-nt864ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCCAAGTGCAACTCGTGGAATCTGGTGGAGGACTCGTGCAA
CCCGGAAGATCGCTTAGACTGTCGTGTGCCGCCAGCGGGTTCACTTTCTCG
AACTACGCGATGTCCTGGGTCCGCCAGGCACCCGGAAAGGGACTCGGTTGG
GTGTCCGGCATTTCCCGGTCCGGCGAAAATACCTACTACGCCGACTCCGTG
AAGGGCCGCTTCACCATCTCAAGGGACAACAGCAAAAACACCCTGTACTTG
CAAATGAACTCCCTGCGGGATGAAGATACAGCCGTGTACTATTGCGCCCGG
TCGCCTGCCCATTACTACGGCGGAATGGACGTCTGGGGACAGGGAACCACT
GTGACTGTCAGCAGCGCGTCGGGTGGCGGCGGCTCAGGGGGTCGGGCCTCC
GGGGGGGGAGGGTCCGACATCGTGCTGACCCAGTCCCCGGGAACCCTGAGC
CTGAGCCCGGGAGAGCGCGCGACCCTGTCATGCCGGGCATCCCAGAGCATT
AGCTCCTCCTTTCTCGCCTGGTATCAGCAGAAGCCCGGACAGGCCCCGAGG
CTGCTGATCTACGGCGCTAGCAGAAGGGCTACCGGAATCCCAGACCGGTTC
TCCGGCTCCGGTTCCGGGACCGATTTCACCCTTACTATCTCGCGCCTGGAA
CCTGAGGACTCCGCCGTCTACTACTGCCAGCAGTACCACTCATCCCCGTCG
TGGACGTTCGGACAGGGCACCAAGCTGGAGATTAAGACCACTACCCCAGCA
CCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTG
CGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGT
CTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGC
GGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGG
AAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACT
ACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGC
GGCTGCGAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTAC
AAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAG
GAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGG
AAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAG
GATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGA
AGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAG
GACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
139105
139105-aa850MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGRSLRLSCAASGFTFD
Full CARDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYL
QMNSLRAEDTALYYCSVHSFLAYWGQGTLVTVSSASGGGGSGGRASGGGGS
DIVMTQTPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQL
LIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPYT
FGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLD
FACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQ
EEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEY
DVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRG
KGHDGLYQGLSTATKDTYDALHMQALPPR
139105-nt865ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCCAAGTGCAACTCGTCGAATCCGGTGGAGGTCTGGTCCAA
CCTGGTAGAAGCCTGAGACTGTCGTGTGCGGCCAGCGGATTCACCTTTGAT
GACTATGCTATGCACTGGGTGCGGCAGGCCCCAGGAAAGGGCCTGGAATGG
GTGTCGGGAATTAGCTGGAACTCCGGGTCCATTGGCTACGCCGACTCCGTG
AAGGGCCGCTTCACCATCTCCCGCGACAACGCAAAGAACTCCCTGTACTTG
CAAATGAACTCGCTCAGGGCTGAGGATACCGCGCTGTACTACTGCTCCGTG
CATTCCTTCCTGGCCTACTGGGGACAGGGAACTCTGGTCACCGTGTCGAGC
GCCTCCGGCGGCGGGGGCTCGGGTGGACGGGCCTCGGGCGGAGGGGGGTCC
GACATCGTGATGACCCAGACCCCGCTGAGCTTGCCCGTGACTCCCGGAGAG
CCTGCATCCATCTCCTGCCGGTCATCCCAGTCCCTTCTCCACTCCAACGGA
TACAACTACCTCGACTGGTACCTCCAGAAGCCGGGACAGAGCCCTCAGCTT
CTGATCTACCTGGGGTCAAATAGAGCCTCAGGAGTGCCGGATCGGTTCAGC
GGATCTGGTTCGGGAACTGATTTCACTCTGAAGATTTCCCGCGTGGAAGCC
GAGGACGTGGGCGTCTACTACTGTATGCAGGCGCTGCAGACCCCCTATACC
TTCGGCCAAGGGACGAAAGTGGAGATCAAGACCACTACCCCAGCACCGAGG
CCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCG
GAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGAC
TTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTC
CTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAG
CTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAA
GAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGC
GAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAG
GGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTAC
GACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCG
CGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAG
ATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGC
AAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACC
TATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
139111
139111-aa851MALPVTALLLPLALLLHAARPEVQLLESGGGLVQPGGSLRLSCAVSGFALS
Full CARNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQ
MNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGS
DIVMTQTPLSLSVTPGQPASISCKSSQSLLRNDGKTPLYWYLQKAGQPPQL
LIYEVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGAYYCMQNIQFPSF
GGGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDF
ACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQE
EDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYD
VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGK
GHDGLYQGLSTATKDTYDALHMQALPPR
139111-nt866ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCGAAGTGCAATTGTTGGAATCTGGAGGAGGACTTGTGCAG
CCTGGAGGATCACTGAGACTTTCGTGTGCGGTGTCAGGCTTCGCCCTGAGC
AACCACGGCATGAGCTGGGTGCGGAGAGCCCCGGGGAAGGGTCTGGAATGG
GTGTCCGGGATCGTCTACTCCGGTTCAACTTACTACGCCGCAAGCGTGAAG
GGTCGCTTCACCATTTCCCGCGATAACTCCCGGAACACCCTGTACCTCCAA
ATGAACTCCCTGCGGCCCGAGGACACCGCCATCTACTACTGTTCCGCGCAT
GGAGGAGAGTCCGATGTCTGGGGACAGGGCACTACCGTGACCGTGTCGAGC
GCCTCGGGGGGAGGAGGCTCCGGCGGTCGCGCCTCCGGGGGGGGTGGCAGC
GACATTGTGATGACGCAGACTCCACTCTCGCTGTCCGTGACCCCGGGACAG
CCCGCGTCCATCTCGTGCAAGAGCTCCCAGAGCCTGCTGAGGAACGACGGA
AAGACTCCTCTGTATTGGTACCTCCAGAAGGCTGGACAGCCCCCGCAACTG
CTCATCTACGAAGTGTCAAATCGCTTCTCCGGGGTGCCGGATCGGTTTTCC
GGCTCGGGATCGGGCACCGACTTCACCCTGAAAATCTCCAGGGTCGAGGCC
GAGGACGTGGGAGCCTACTACTGCATGCAAAACATCCAGTTCCCTTCCTTC
GGCGGCGGCACAAAGCTGGAGATTAAGACCACTACCCCAGCACCGAGGCCA
CCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAG
GCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTC
GCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTG
CTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTG
CTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAG
GAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAA
CTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGG
CAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGAC
GTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGC
AGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATG
GCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAA
GGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTAT
GACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
139100
139100-aa852MALPVTALLLPLALLLHAARPQVQLVQSGAEVRKTGASVKVSCKASGYIFD
Full CARNEGINWVRQAPGQGLEWMGWINPKNNNTNYAQKFQGRVTITADESTNTAYM
EVSSLRSEDTAVYYCARGPYYYQSYMDVWGQGTMVTVSSASGGGGSGGRAS
GGGGSDIVMTQTPLSLPVTPGEPASISCRSSQSLLHSNGYNYLNWYLQKPG
QSPQLLIYLGSKRASGVPDRFSGSGSGTDFTLHITRVGAEDVGVYYCMQAL
QTPYTFGQGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVH
TRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRP
VQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLG
RREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKG
ERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR
139100-nt867ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCCAAGTCCAACTCGTCCAGTCCGGCGCAGAAGTCAGAAAA
ACCGGTGCTAGCGTGAAAGTGTCCTGCAAGGCCTCCGGCTACATTTTCGAT
AACTTCGGAATCAACTGGGTCAGACAGGCCCCGGGCCAGGGGCTGGAATGG
ATGGGATGGATCAACCCCAAGAACAACAACACCAACTACGCACAGAAGTTC
CAGGGCCGCGTGACTATCACCGCCGATGAATCGACCAATACCGCCTACATG
GAGGTGTCCTCCCTGCGGTCGGAGGACACTGCCGTGTATTACTGCGCGAGG
GGCCCATACTACTACCAAAGCTACATGGACGTCTGGGGACAGGGAACCATG
GTGACCGTGTCATCCGCCTCCGGTGGTGGAGGCTCCGGGGGGCGGGCTTCA
GGAGGCGGAGGAAGCGATATTGTGATGACCCAGACTCCGCTTAGCCTGCCC
GTGACTCCTGGAGAACCGGCCTCCATTTCCTGCCGGTCCTCGCAATCACTC
CTGCATTCCAACGGTTACAACTACCTGAATTGGTACCTCCAGAAGCCTGGC
CAGTCGCCCCAGTTGCTGATCTATCTGGGCTCGAAGCGCGCCTCCGGGGTG
CCTGACCGGTTTAGCGGATCTGGGAGCGGCACGGACTTCACTCTCCACATC
ACCCGCGTGGGAGCGGAGGACGTGGGAGTGTACTACTGTATGCAGGCGCTG
CAGACTCCGTACACATTCGGACAGGGCACCAAGCTGGAGATCAAGACCACT
ACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCT
CTGTCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCAT
ACCCGGGGTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCT
GGTACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAG
CGCGGTCGGAAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCT
GTGCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAG
GAGGAAGGCGGCTGCGAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCT
CCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGT
CGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAA
ATGGGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAG
CTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGG
GAACGCAGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACC
GCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
139101
139101-aa853MALPVTALLLPLALLLHAARPQVQLQESGGGLVQPGGSLRLSCAASGFTFS
Full CARSDAMTWVRQAPGKGLEWVSVISGSGGTTYYADSVKGRFTISRDNSKNTLYL
QMNSLRAEDTAVYYCAKLDSSGYYYARGPRYWGQGTLVTVSSASGGGGSGG
RASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKA
PKLLIYGASTLASGVPARFSGSGSGTHFTLTINSLQSEDSATYYCQQSYKR
ASFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRG
LDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQT
TQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRRE
EYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR
RGKGHDGLYQGLSTATKDTYDALHMQALPPR
139101-nt868ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCCAAGTGCAACTTCAAGAATCAGGCGGAGGACTCGTGCAG
CCCGGAGGATCATTGCGGCTCTCGTGCGCCGCCTCGGGCTTCACCTTCTCG
AGCGACGCCATGACCTGGGTCCGCCAGGCCCCGGGGAAGGGGCTGGAATGG
GTGTCTGTGATTTCCGGCTCCGGGGGAACTACGTACTACGCCGATTCCGTG
AAAGGTCGCTTCACTATCTCCCGGGACAACAGCAAGAACACCCTTTATCTG
CAAATGAATTCCCTCCGCGCCGAGGACACCGCCGTGTACTACTGCGCCAAG
CTGGACTCCTCGGGCTACTACTATGCCCGGGGTCCGAGATACTGGGGACAG
GGAACCCTCGTGACCGTGTCCTCCGCGTCCGGCGGAGGAGGGTCGGGAGGG
CGGGCCTCCGGCGGCGGCGGTTCGGACATCCAGCTGACCCAGTCCCCATCC
TCACTGAGCGCAAGCGTGGGCGACAGAGTCACCATTACATGCAGGGCGTCC
CAGAGCATCAGCTCCTACCTGAACTGGTACCAACAGAAGCCTGGAAAGGCT
CCTAAGCTGTTGATCTACGGGGCTTCGACCCTGGCATCCGGGGTGCCCGCG
AGGTTTAGCGGAAGCGGTAGCGGCACTCACTTCACTCTGACCATTAACAGC
CTCCAGTCCGAGGATTCAGCCACTTACTACTGTCAGCAGTCCTACAAGCGG
GCCAGCTTCGGACAGGGCACTAAGGTCGAGATCAAGACCACTACCCCAGCA
CCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTG
CGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGT
CTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGC
GGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGG
AAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACT
ACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGC
GGCTGCGAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTAC
AAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAG
GAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGG
AAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAG
GATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGA
AGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAG
GACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
139102
139102-aa854MALPVTALLLPLALLLHAARPQVQLVQSGAEVKKPGASVKVSCKASGYTFS
Full CARNYGITWVRQAPGQGLEWMGWISAYNGNTNYAQKFQGRVTMTRNTSISTAYM
ELSSLRSEDTAVYYCARGPYYYYMDVWGKGTMVTVSSASGGGGSGGRASGG
GGSEIVMTQSPLSLPVTPGEPASISCRSSQSLLYSNGYNYVDWYLQKPGQS
PQLLIYLGSNRASGVPDRFSGSGSGTDFKLQISRVEAEDVGIYYCMQGRQF
PYSFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTR
GLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQ
TTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRR
EEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGER
RRGKGHDGLYQGLSTATKDTYDALHMQALPPR
139102-nt869ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCCAAGTCCAACTGGTCCAGAGCGGTGCAGAAGTGAAGAAG
CCCGGAGCGAGCGTGAAAGTGTCCTGCAAGGCTTCCGGGTACACCTTCTCC
AACTACGGCATCACTTGGGTGCGCCAGGCCCCGGGACAGGGCCTGGAATGG
ATGGGGTGGATTTCCGCGTACAACGGCAATACGAACTACGCTCAGAAGTTC
CAGGGTAGAGTGACCATGACTAGGAACACCTCCATTTCCACCGCCTACATG
GAACTGTCCTCCCTGCGGAGCGAGGACACCGCCGTGTACTATTGCGCCCGG
GGACCATACTACTACTACATGGATGTCTGGGGGAAGGGGACTATGGTCACC
GTGTCATCCGCCTCGGGAGGCGGCGGATCAGGAGGACGCGCCTCTGGTGGT
GGAGGATCGGAGATCGTGATGACCCAGAGCCCTCTCTCCTTGCCCGTGACT
CCTGGGGAGCCCGCATCCATTTCATGCCGGAGCTCCCAGTCACTTCTCTAC
TCCAACGGCTATAACTACGTGGATTGGTACCTCCAAAAGCCGGGCCAGAGC
CCGCAGCTGCTGATCTACCTGGGCTCGAACAGGGCCAGCGGAGTGCCTGAC
CGGTTCTCCGGGTCGGGAAGCGGGACCGACTTCAAGCTGCAAATCTCGAGA
GTGGAGGCCGAGGACGTGGGAATCTACTACTGTATGCAGGGCCGCCAGTTT
CCGTACTCGTTCGGACAGGGCACCAAAGTGGAAATCAAGACCACTACCCCA
GCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCC
CTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGG
GGTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACT
TGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGT
CGGAAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAG
ACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAA
GGCGGCTGCGAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCC
TACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGA
GAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGC
GGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAA
AAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGC
AGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACC
AAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
139104
139104-aa855MALPVTALLLPLALLLHAARPEVQLLETGGGLVQPGGSLRLSCAVSGFALS
Full CARNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQ
MNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGS
EIVLTQSPATLSVSPGESATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGA
STRASGIPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYGSSLTFGGGTK
VEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIY
IWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCS
CRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKR
RGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGL
YQGLSTATKDTYDALHMQALPPR
139104-nt870ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCGAAGTGCAATTGCTCGAAACTGGAGGAGGTCTGGTGCAA
CCTGGAGGATCACTTCGCCTGTCCTGCGCCGTGTCGGGCTTTGCCCTGTCC
AACCATGGAATGAGCTGGGTCCGCCGCGCGCCGGGGAAGGGCCTCGAATGG
GTGTCCGGCATCGTCTACTCCGGCTCCACCTACTACGCCGCGTCCGTGAAG
GGCCGGTTCACGATTTCACGGGACAACTCGCGGAACACCCTGTACCTCCAA
ATGAATTCCCTTCGGCCGGAGGATACTGCCATCTACTACTGCTCCGCCCAC
GGTGGCGAATCCGACGTCTGGGGCCAGGGAACCACCGTGACCGTGTCCAGC
GCGTCCGGGGGAGGAGGAAGCGGGGGTAGAGCATCGGGTGGAGGCGGATCA
GAGATCGTGCTGACCCAGTCCCCCGCCACCTTGAGCGTGTCACCAGGAGAG
TCCGCCACCCTGTCATGCCGCGCCAGCCAGTCCGTGTCCTCCAACCTGGCT
TGGTACCAGCAGAAGCCGGGGCAGGCCCCTAGACTCCTGATCTATGGGGCG
TCGACCCGGGCATCTGGAATTCCCGATAGGTTCAGCGGATCGGGCTCGGGC
ACTGACTTCACTCTGACCATCTCCTCGCTGCAAGCCGAGGACGTGGCTGTG
TACTACTGTCAGCAGTACGGAAGCTCCCTGACTTTCGGTGGCGGGACCAAA
GTCGAGATTAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCT
ACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCCGCA
GCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTCGCCTGCGATATCTAC
ATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTCGTG
ATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTAAG
CAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGTTCA
TGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGCGTGAAATTC
AGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTCTAC
AACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGG
AGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCCCAA
GAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGC
GAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAAGGCCACGACGGACTG
TACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATG
CAGGCCCTGCCGCCTCGG
139106
139106-aa856MALPVTALLLPLALLLHAARPEVQLVETGGGLVQPGGSLRLSCAVSGFALS
Full CARNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQ
MNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGS
EIVMTQSPATLSVSPGERATLSCRASQSVSSKLAWYQQKPGQAPRLLMYGA
SIRATGIPDRFSGSGSGTEFTLTISSLEPEDFAVYYCQQYGSSSWIFGQGT
KVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDI
YIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGC
SCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDK
RRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDG
LYQGLSTATKDTYDALHMQALPPR
139106-nt871ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCGAAGTGCAATTGGTGGAAACTGGAGGAGGACTTGTGCAA
CCTGGAGGATCATTGAGACTGAGCTGCGCAGTGTCGGGATTCGCCCTGAGC
AACCATGGAATGTCCTGGGTCAGAAGGGCCCCTGGAAAAGGCCTCGAATGG
GTGTCAGGGATCGTGTACTCCGGTTCCACTTACTACGCCGCCTCCGTGAAG
GGGCGCTTCACTATCTCACGGGATAACTCCCGCAATACCCTGTACCTCCAA
ATGAACAGCCTGCGGCCGGAGGATACCGCCATCTACTACTGTTCCGCCCAC
GGTGGAGAGTCTGACGTCTGGGGCCAGGGAACTACCGTGACCGTGTCCTCC
GCGTCCGGCGGTGGAGGGAGCGGCGGCCGCGCCAGCGGCGGCGGAGGCTCC
GAGATCGTGATGACCCAGAGCCCCGCTACTCTGTCGGTGTCGCCCGGAGAA
AGGGCGACCCTGTCCTGCCGGGCGTCGCAGTCCGTGAGCAGCAAGCTGGCT
TGGTACCAGCAGAAGCCGGGCCAGGCACCACGCCTGCTTATGTACGGTGCC
TCCATTCGGGCCACCGGAATCCCGGACCGGTTCTCGGGGTCGGGGTCCGGT
ACCGAGTTCACACTGACCATTTCCTCGCTCGAGCCCGAGGACTTTGCCGTC
TATTACTGCCAGCAGTACGGCTCCTCCTCATGGACGTTCGGCCAGGGGACC
AAGGTCGAAATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCT
CCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCC
GCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTCGCCTGCGATATC
TACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTC
GTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTT
AAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGT
TCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGCGTGAAA
TTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTC
TACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAG
CGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCC
CAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTAT
AGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAAGGCCACGACGGA
CTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCAC
ATGCAGGCCCTGCCGCCTCGG
139107
139107-aa857MALPVTALLLPLALLLHAARPEVQLVETGGGVVQPGGSLRLSCAVSGFALS
Full CARNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQ
MNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGS
EIVLTQSPGTLSLSPGERATLSCRASQSVGSTNLAWYQQKPGQAPRLLIYD
ASNRATGIPDRFSGGGSGTDFTLTISRLEPEDFAVYYCQQYGSSPPWTFGQ
GTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFAC
DIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEED
GCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVL
DKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGH
DGLYQGLSTATKDTYDALHMQALPPR
139107-nt872ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCGAAGTGCAATTGGTGGAGACTGGAGGAGGAGTGGTGCAA
CCTGGAGGAAGCCTGAGACTGTCATGCGCGGTGTCGGGCTTCGCCCTCTCC
AACCACGGAATGTCCTGGGTCCGCCGGGCCCCTGGGAAAGGACTTGAATGG
GTGTCCGGCATCGTGTACTCGGGTTCCACCTACTACGCGGCCTCAGTGAAG
GGCCGGTTTACTATTAGCCGCGACAACTCCAGAAACACACTGTACCTCCAA
ATGAACTCGCTGCGGCCGGAAGATACCGCTATCTACTACTGCTCCGCCCAT
GGGGGAGAGTCGGACGTCTGGGGACAGGGCACCACTGTCACTGTGTCCAGC
GCTTCCGGCGGTGGTGGAAGCGGGGGACGGGCCTCAGGAGGCGGTGGCAGC
GAGATTGTGCTGACCCAGTCCCCCGGGACCCTGAGCCTGTCCCCGGGAGAA
AGGGCCACCCTCTCCTGTCGGGCATCCCAGTCCGTGGGGTCTACTAACCTT
GCATGGTACCAGCAGAAGCCCGGCCAGGCCCCTCGCCTGCTGATCTACGAC
GCGTCCAATAGAGCCACCGGCATCCCGGATCGCTTCAGCGGAGGCGGATCG
GGCACCGACTTCACCCTCACCATTTCAAGGCTGGAACCGGAGGACTTCGCC
GTGTACTACTGCCAGCAGTATGGTTCGTCCCCACCCTGGACGTTCGGCCAG
GGGACTAAGGTCGAGATCAAGACCACTACCCCAGCACCGAGGCCACCCACC
CCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGT
AGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTCGCCTGC
GATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTT
TCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTAC
ATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGAC
GGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGC
GTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAAC
CAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTG
GACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAG
AATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAA
GCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAAGGCCAC
GACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCT
CTTCACATGCAGGCCCTGCCGCCTCGG
139108
139108-aa858MALPVTALLLPLALLLHAARPQVQLVESGGGLVKPGGSLRLSCAASGFTFS
Full CARDYYMSWIRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYL
QMNSLRAEDTAVYYCARESGDGMDVWGQGTTVTVSSASGGGGSGGRASGGG
GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY
AASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTLAFGQGT
KVDIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDI
YIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGC
SCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDK
RRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDG
LYQGLSTATKDTYDALHMQALPPR
139108-nt873ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCCAAGTGCAACTCGTGGAATCTGGTGGAGGACTCGTGAAA
CCTGGAGGATCATTGAGACTGTCATGCGCGGCCTCGGGATTCACGTTCTCC
GATTACTACATGAGCTGGATTCGCCAGGCTCCGGGGAAGGGACTGGAATGG
GTGTCCTACATTTCCTCATCCGGCTCCACCATCTACTACGCGGACTCCGTG
AAGGGGAGATTCACCATTAGCCGCGATAACGCCAAGAACAGCCTGTACCTT
CAGATGAACTCCCTGCGGGCTGAAGATACTGCCGTCTACTACTGCGCAAGG
GAGAGCGGAGATGGGATGGACGTCTGGGGACAGGGTACCACTGTGACCGTG
TCGTCGGCCTCCGGCGGAGGGGGTTCGGGTGGAAGGGCCAGCGGCGGCGGA
GGCAGCGACATCCAGATGACCCAGTCCCCCTCATCGCTGTCCGCCTCCGTG
GGCGACCGCGTCACCATCACATGCCGGGCCTCACAGTCGATCTCCTCCTAC
CTCAATTGGTATCAGCAGAAGCCCGGAAAGGCCCCTAAGCTTCTGATCTAC
GCAGCGTCCTCCCTGCAATCCGGGGTCCCATCTCGGTTCTCCGGCTCGGGC
AGCGGTACCGACTTCACTCTGACCATCTCGAGCCTGCAGCCGGAGGACTTC
GCCACTTACTACTGTCAGCAAAGCTACACCCTCGCGTTTGGCCAGGGCACC
AAAGTGGACATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCT
CCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCC
GCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTCGCCTGCGATATC
TACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTC
GTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTT
AAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGT
TCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGCGTGAAA
TTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTC
TACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAG
CGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCC
CAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTAT
AGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAAGGCCACGACGGA
CTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCAC
ATGCAGGCCCTGCCGCCTCGG
139110
139110-aa860MALPVTALLLPLALLLHAARPQVQLVQSGGGLVKPGGSLRLSCAASGFTFS
Full CARDYYMSWIRQAPGKGLEWVSYISSSGNTIYYADSVKGRFTISRDNAKNSLYL
QMNSLRAEDTAVYYCARSTMVREDYWGQGTLVTVSSASGGGGSGGRASGGG
GSDIVLTQSPLSLPVTLGQPASISCKSSESLVHNSGKTYLNWFHQRPGQSP
RRLIYEVSNRDSGVPDRFTGSGSGTDFTLKISRVEAEDVGVYYCMQGTHWP
GTFGQGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRG
LDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQT
TQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRRE
EYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR
RGKGHDGLYQGLSTATKDTYDALHMQALPPR
139110-nt875ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCCAAGTGCAACTGGTGCAAAGCGGAGGAGGATTGGTCAAA
CCCGGAGGAAGCCTGAGACTGTCATGCGCGGCCTCTGGATTCACCTTCTCC
GATTACTACATGTCATGGATCAGACAGGCCCCGGGGAAGGGCCTCGAATGG
GTGTCCTACATCTCGTCCTCCGGGAACACCATCTACTACGCCGACAGCGTG
AAGGGCCGCTTTACCATTTCCCGCGACAACGCAAAGAACTCGCTGTACCTT
CAGATGAATTCCCTGCGGGCTGAAGATACCGCGGTGTACTATTGCGCCCGG
TCCACTATGGTCCGGGAGGACTACTGGGGACAGGGCACACTCGTGACCGTG
TCCAGCGCGAGCGGGGGTGGAGGCAGCGGTGGACGCGCCTCCGGCGGCGGC
GGTTCAGACATCGTGCTGACTCAGTCGCCCCTGTCGCTGCCGGTCACCCTG
GGCCAACCGGCCTCAATTAGCTGCAAGTCCTCGGAGAGCCTGGTGCACAAC
TCAGGAAAGACTTACCTGAACTGGTTCCATCAGCGGCCTGGACAGTCCCCA
CGGAGGCTCATCTATGAAGTGTCCAACAGGGATTCGGGGGTGCCCGACCGC
TTCACTGGCTCCGGGTCCGGCACCGACTTCACCTTGAAAATCTCCAGAGTG
GAAGCCGAGGACGTGGGCGTGTACTACTGTATGCAGGGTACCCACTGGCCT
GGAACCTTTGGACAAGGAACTAAGCTCGAGATTAAGACCACTACCCCAGCA
CCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTG
CGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGT
CTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGC
GGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGG
AAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACT
ACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGC
GGCTGCGAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTAC
AAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAG
GAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGG
AAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAG
GATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGA
AGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAG
GACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
139112
139112-aa861MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGGSLRLSCAVSGFALS
Full CARNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQ
MNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGS
DIRLTQSPSPLSASVGDRVTITCQASEDINKFLNWYHQTPGKAPKLLIYDA
STLQTGVPSRFSGSGSGTDFTLTINSLQPEDIGTYYCQQYESLPLTFGGGT
KVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDI
YIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGC
SCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDK
RRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDG
LYQGLSTATKDTYDALHMQALPPR
139112-nt876ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCCAAGTGCAACTCGTGGAATCTGGTGGAGGACTCGTGCAA
CCCGGTGGAAGCCTTAGGCTGTCGTGCGCCGTCAGCGGGTTTGCTCTGAGC
AACCATGGAATGTCCTGGGTCCGCCGGGCACCGGGAAAAGGGCTGGAATGG
GTGTCCGGCATCGTGTACAGCGGGTCAACCTATTACGCCGCGTCCGTGAAG
GGCAGATTCACTATCTCAAGAGACAACAGCCGGAACACCCTGTACTTGCAA
ATGAATTCCCTGCGCCCCGAGGACACCGCCATCTACTACTGCTCCGCCCAC
GGAGGAGAGTCGGACGTGTGGGGCCAGGGAACGACTGTGACTGTGTCCAGC
GCATCAGGAGGGGGTGGTTCGGGCGGCCGGGCCTCGGGGGGAGGAGGTTCC
GACATTCGGCTGACCCAGTCCCCGTCCCCACTGTCGGCCTCCGTCGGCGAC
CGCGTGACCATCACTTGTCAGGCGTCCGAGGACATTAACAAGTTCCTGAAC
TGGTACCACCAGACCCCTGGAAAGGCCCCCAAGCTGCTGATCTACGATGCC
TCGACCCTTCAAACTGGAGTGCCTAGCCGGTTCTCCGGGTCCGGCTCCGGC
ACTGATTTCACTCTGACCATCAACTCATTGCAGCCGGAAGATATCGGGACC
TACTATTGCCAGCAGTACGAATCCCTCCCGCTCACATTCGGCGGGGGAACC
AAGGTCGAGATTAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCT
CCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCC
GCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTCGCCTGCGATATC
TACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTC
GTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTT
AAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGT
TCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGCGTGAAA
TTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTC
TACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAG
CGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCC
CAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTAT
AGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAAGGCCACGACGGA
CTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCAC
ATGCAGGCCCTGCCGCCTCGG
139113
139113-aa862MALPVTALLLPLALLLHAARPEVQLVETGGGLVQPGGSLRLSCAVSGFALS
Full CARNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQ
MNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGS
ETTLTQSPATLSVSPGERATLSCRASQSVGSNLAWYQQKPGQGPRLLIYGA
STRATGIPARFSGSGSGTEFTLTISSLQPEDFAVYYCQQYNDWLPVTFGQG
TKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD
IYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDG
CSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLD
KRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHD
GLYQGLSTATKDTYDALHMQALPPR
139113-nt877ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCGAAGTGCAATTGGTGGAAACTGGAGGAGGACTTGTGCAA
CCTGGAGGATCATTGCGGCTCTCATGCGCTGTCTCCGGCTTCGCCCTGTCA
AATCACGGGATGTCGTGGGTCAGACGGGCCCCGGGAAAGGGTCTGGAATGG
GTGTCGGGGATTGTGTACAGCGGCTCCACCTACTACGCCGCTTCGGTCAAG
GGCCGCTTCACTATTTCACGGGACAACAGCCGCAACACCCTCTATCTGCAA
ATGAACTCTCTCCGCCCGGAGGATACCGCCATCTACTACTGCTCCGCACAC
GGCGGCGAATCCGACGTGTGGGGACAGGGAACCACTGTCACCGTGTCGTCC
GCATCCGGTGGCGGAGGATCGGGTGGCCGGGCCTCCGGGGGCGGCGGCAGC
GAGACTACCCTGACCCAGTCCCCTGCCACTCTGTCCGTGAGCCCGGGAGAG
AGAGCCACCCTTAGCTGCCGGGCCAGCCAGAGCGTGGGCTCCAACCTGGCC
TGGTACCAGCAGAAGCCAGGACAGGGTCCCAGGCTGCTGATCTACGGAGCC
TCCACTCGCGCGACCGGCATCCCCGCGAGGTTCTCCGGGTCGGGTTCCGGG
ACCGAGTTCACCCTGACCATCTCCTCCCTCCAACCGGAGGACTTCGCGGTG
TACTACTGTCAGCAGTACAACGATTGGCTGCCCGTGACATTTGGACAGGGG
ACGAAGGTGGAAATCAAAACCACTACCCCAGCACCGAGGCCACCCACCCCG
GCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGA
CCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTCGCCTGCGAT
ATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCA
CTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATC
TTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGC
TGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGCGTG
AAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAG
CTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGAC
AAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAAT
CCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCC
TATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAAGGCCACGAC
GGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTT
CACATGCAGGCCCTGCCGCCTCGG
139114
139114-aa863MALPVTALLLPLALLLHAARPEVQLVESGGGLVQPGGSLRLSCAVSGFALS
Full CARNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQ
MNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGS
EIVLTQSPGTLSLSPGERATLSCRASQSIGSSSLAWYQQKPGQAPRLLMYG
ASSRASGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYAGSPPFTFGQ
GTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFAC
DIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEED
GCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVL
DKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGH
DGLYQGLSTATKDTYDALHMQALPPR
139114-nt878ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCGAAGTGCAATTGGTGGAATCTGGTGGAGGACTTGTGCAA
CCTGGAGGATCACTGAGACTGTCATGCGCGGTGTCCGGTTTTGCCCTGAGC
AATCATGGGATGTCGTGGGTCCGGCGCGCCCCCGGAAAGGGTCTGGAATGG
GTGTCGGGTATCGTCTACTCCGGGAGCACTTACTACGCCGCGAGCGTGAAG
GGCCGCTTCACCATTTCCCGCGATAACTCCCGCAACACCCTGTACTTGCAA
ATGAACTCGCTCCGGCCTGAGGACACTGCCATCTACTACTGCTCCGCACAC
GGAGGAGAATCCGACGTGTGGGGCCAGGGAACTACCGTGACCGTCAGCAGC
GCCTCCGGCGGCGGGGGCTCAGGCGGACGGGCTAGCGGCGGCGGTGGCTCC
GAGATCGTGCTGACCCAGTCGCCTGGCACTCTCTCGCTGAGCCCCGGGGAA
AGGGCAACCCTGTCCTGTCGGGCCAGCCAGTCCATTGGATCATCCTCCCTC
GCCTGGTATCAGCAGAAACCGGGACAGGCTCCGCGGCTGCTTATGTATGGG
GCCAGCTCAAGAGCCTCCGGCATTCCCGACCGGTTCTCCGGGTCCGGTTCC
GGCACCGATTTCACCCTGACTATCTCGAGGCTGGAGCCAGAGGACTTCGCC
GTGTACTACTGCCAGCAGTACGCGGGGTCCCCGCCGTTCACGTTCGGACAG
GGAACCAAGGTCGAGATCAAGACCACTACCCCAGCACCGAGGCCACCCACC
CCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGT
AGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTCGCCTGC
GATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTT
TCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTAC
ATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGAC
GGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGC
GTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAAC
CAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTG
GACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAG
AATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAA
GCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAAGGCCAC
GACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCT
CTTCACATGCAGGCCCTGCCGCCTCGG
149362
149362-aa879MALPVTALLLPLALLLHAARPQVQLQESGPGLVKPSETLSLTCTVSGGSIS
Full CARSSYYYWGWIRQPPGKGLEWIGSIYYSGSAYYNPSLKSRVTISVDTSKNQFS
LRLSSVTAADTAVYYCARHWQEWPDAFDIWGQGTMVTVSSGGGGSGGGGSG
GGGSETTLTQSPAFMSATPGDKVIISCKASQDIDDAMNWYQQKPGEAPLFI
IQSATSPVPGIPPRFSGSGFGTDFSLTINNIESEDAAYYFCLQHDNFPLTF
GQGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDF
ACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQE
EDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYD
VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGK
GHDGLYQGLSTATKDTYDALHMQALPPR
149362-nt901ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCCAAGTGCAGCTTCAGGAAAGCGGACCGGGCCTGGTCAAG
CCATCCGAAACTCTCTCCCTGACTTGCACTGTGTCTGGCGGTTCCATCTCA
TCGTCGTACTACTACTGGGGCTGGATTAGGCAGCCGCCCGGAAAGGGACTG
GAGTGGATCGGAAGCATCTACTATTCCGGCTCGGCGTACTACAACCCTAGC
CTCAAGTCGAGAGTGACCATCTCCGTGGATACCTCCAAGAACCAGTTTTCC
CTGCGCCTGAGCTCCGTGACCGCCGCTGACACCGCCGTGTACTACTGTGCT
CGGCATTGGCAGGAATGGCCCGATGCCTTCGACATTTGGGGCCAGGGCACT
ATGGTCACTGTGTCATCCGGGGGTGGAGGCAGCGGGGGAGGAGGGTCCGGG
GGGGGAGGTTCAGAGACAACCTTGACCCAGTCACCCGCATTCATGTCCGCC
ACTCCGGGAGACAAGGTCATCATCTCGTGCAAAGCGTCCCAGGATATCGAC
GATGCCATGAATTGGTACCAGCAGAAGCCTGGCGAAGCGCCGCTGTTCATT
ATCCAATCCGCAACCTCGCCCGTGCCTGGAATCCCACCGCGGTTCAGCGGC
AGCGGTTTCGGAACCGACTTTTCCCTGACCATTAACAACATTGAGTCCGAG
GACGCCGCCTACTACTTCTGCCTGCAACACGACAACTTCCCTCTCACGTTC
GGCCAGGGAACCAAGCTGGAAATCAAGACCACTACCCCAGCACCGAGGCCA
CCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAG
GCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTC
GCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTG
CTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTG
CTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAG
GAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAA
CTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGG
CAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGAC
GTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGC
AGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATG
GCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAA
GGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTAT
GACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
149363
149363-aa880MALPVTALLLPLALLLHAARPQVNLRESGPALVKPTQTLTLTCTFSGFSLR
Full CARTSGMCVSWIRQPPGKALEWLARIDWDEDKFYSTSLKTRLTISKDTSDNQVV
LRMTNMDPADTATYYCARSGAGGTSATAFDIWGPGTMVTVSSGGGGSGGGG
SGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDIYNNLAWFQLKPGSAPR
SLMYAANKSQSGVPSRFSGSASGTDFTLTISSLQPEDFATYYCQHYYRFPY
SFGQGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGL
DFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTT
QEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREE
YDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRR
GKGHDGLYQGLSTATKDTYDALHMQALPPR
149363-nt902ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCCAAGTCAATCTGCGCGAATCCGGCCCCGCCTTGGTCAAG
CCTACCCAGACCCTCACTCTGACCTGTACTTTCTCCGGCTTCTCCCTGCGG
ACTTCCGGGATGTGCGTGTCCTGGATCAGACAGCCTCCGGGAAAGGCCCTG
GAGTGGCTCGCTCGCATTGACTGGGATGAGGACAAGTTCTACTCCACCTCA
CTCAAGACCAGGCTGACCATCAGCAAAGATACCTCTGACAACCAAGTGGTG
CTCCGCATGACCAACATGGACCCAGCCGACACTGCCACTTACTACTGCGCG
AGGAGCGGAGCGGGCGGAACCTCCGCCACCGCCTTCGATATTTGGGGCCCG
GGTACCATGGTCACCGTGTCAAGCGGAGGAGGGGGGTCCGGGGGCGGCGGT
TCCGGGGGAGGCGGATCGGACATTCAGATGACTCAGTCACCATCGTCCCTG
AGCGCTAGCGTGGGCGACAGAGTGACAATCACTTGCCGGGCATCCCAGGAC
ATCTATAACAACCTTGCGTGGTTCCAGCTGAAGCCTGGTTCCGCACCGCGG
TCACTTATGTACGCCGCCAACAAGAGCCAGTCGGGAGTGCCGTCCCGGTTT
TCCGGTTCGGCCTCGGGAACTGACTTCACCCTGACGATCTCCAGCCTGCAA
CCCGAGGATTTCGCCACCTACTACTGCCAGCACTACTACCGCTTTCCCTAC
TCGTTCGGACAGGGAACCAAGCTGGAAATCAAGACCACTACCCCAGCACCG
AGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGT
CCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTT
GACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGG
GTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAG
AAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACT
CAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGC
TGCGAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAG
CAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAG
TACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAG
CCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGAT
AAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGA
GGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGAC
ACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
149364
149364-aa881MALPVTALLLPLALLLHAARPEVQLVESGGGLVKPGGSLRLSCAASGFTFS
Full CARSYSMNWVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTISRDNAKNSLYL
QMNSLRAEDTAVYYCAKTIAAVYAFDIWGQGTTVTVSSGGGGSGGGGSGGG
GSEIVLTQSPLSLPVTPEEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSP
QLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTP
YTFGQGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRG
LDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQT
TQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRRE
EYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR
RGKGHDGLYQGLSTATKDTYDALHMQALPPR
149364-nt903ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCGAAGTGCAGCTTGTCGAATCCGGGGGGGGACTGGTCAAG
CCGGGCGGATCACTGAGACTGTCCTGCGCCGCGAGCGGCTTCACGTTCTCC
TCCTACTCCATGAACTGGGTCCGCCAAGCCCCCGGGAAGGGACTGGAATGG
GTGTCCTCTATCTCCTCGTCGTCGTCCTACATCTACTACGCCGACTCCGTG
AAGGGAAGATTCACCATTTCCCGCGACAACGCAAAGAACTCACTGTACTTG
CAAATGAACTCACTCCGGGCCGAAGATACTGCTGTGTACTATTGCGCCAAG
ACTATTGCCGCCGTCTACGCTTTCGACATCTGGGGCCAGGGAACCACCGTG
ACTGTGTCGTCCGGTGGTGGTGGCTCGGGCGGAGGAGGAAGCGGCGGCGGG
GGGTCCGAGATTGTGCTGACCCAGTCGCCACTGAGCCTCCCTGTGACCCCC
GAGGAACCCGCCAGCATCAGCTGCCGGTCCAGCCAGTCCCTGCTCCACTCC
AACGGATACAATTACCTCGATTGGTACCTTCAGAAGCCTGGACAAAGCCCG
CAGCTGCTCATCTACTTGGGATCAAACCGCGCGTCAGGAGTGCCTGACCGG
TTCTCCGGCTCGGGCAGCGGTACCGATTTCACCCTGAAAATCTCCAGGGTG
GAGGCAGAGGACGTGGGAGTGTATTACTGTATGCAGGCGCTGCAGACTCCG
TACACATTTGGGCAGGGCACCAAGCTGGAGATCAAGACCACTACCCCAGCA
CCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTG
CGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGT
CTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGC
GGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGG
AAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACT
ACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGC
GGCTGCGAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTAC
AAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAG
GAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGG
AAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAG
GATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGA
AGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAG
GACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
149365
149365-aa882MALPVTALLLPLALLLHAARPEVQLVESGGGLVKPGGSLRLSCAASGFTFS
Full CARDYYMSWIRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYL
QMNSLRAEDTAVYYCARDLRGAFDIWGQGTMVTVSSGGGGSGGGGSGGGGS
SYVLTQSPSVSAAPGYTATISCGGNNIGTKSVHWYQQKPGQAPLLVIRDDS
VRPSKIPGRFSGSNSGNMATLTISGVQAGDEADFYCQVWDSDSEHVVEGGG
TKLTVLTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD
IYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDG
CSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLD
KRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHD
GLYQGLSTATKDTYDALHMQALPPR
149365-nt904ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCGAAGTCCAGCTCGTGGAGTCCGGCGGAGGCCTTGTGAAG
CCTGGAGGTTCGCTGAGACTGTCCTGCGCCGCCTCCGGCTTCACCTTCTCC
GACTACTACATGTCCTGGATCAGACAGGCCCCGGGAAAGGGCCTGGAATGG
GTGTCCTACATCTCGTCATCGGGCAGCACTATCTACTACGCGGACTCAGTG
AAGGGGCGGTTCACCATTTCCCGGGATAACGCGAAGAACTCGCTGTATCTG
CAAATGAACTCACTGAGGGCCGAGGACACCGCCGTGTACTACTGCGCCCGC
GATCTCCGCGGGGCATTTGACATCTGGGGACAGGGAACCATGGTCACAGTG
TCCAGCGGAGGGGGAGGATCGGGTGGCGGAGGTTCCGGGGGTGGAGGCTCC
TCCTACGTGCTGACTCAGAGCCCAAGCGTCAGCGCTGCGCCCGGTTACACG
GCAACCATCTCCTGTGGCGGAAACAACATTGGGACCAAGTCTGTGCACTGG
TATCAGCAGAAGCCGGGCCAAGCTCCCCTGTTGGTGATCCGCGATGACTCC
GTGCGGCCTAGCAAAATTCCGGGACGGTTCTCCGGCTCCAACAGCGGCAAT
ATGGCCACTCTCACCATCTCGGGAGTGCAGGCCGGAGATGAAGCCGACTTC
TACTGCCAAGTCTGGGACTCAGACTCCGAGCATGTGGTGTTCGGGGGCGGA
ACCAAGCTGACTGTGCTCACCACTACCCCAGCACCGAGGCCACCCACCCCG
GCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGA
CCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTCGCCTGCGAT
ATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCA
CTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATC
TTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGC
TGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGCGTG
AAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAG
CTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGAC
AAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAAT
CCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCC
TATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAAGGCCACGAC
GGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTT
CACATGCAGGCCCTGCCGCCTCGG
149366
149366-aa883MALPVTALLLPLALLLHAARPQVQLVQSGAEVKKPGASVKVSCKPSGYTVT
Full CARSHYTHWVRRAPGQGLEWMGMINPSGGVTAYSQTLQGRVTMTSDTSSSTVYM
ELSSLRSEDTAMYYCAREGSGSGWYFDFWGRGTLVTVSSGGGGSGGGGSGG
GGSSYVLTQPPSVSVSPGQTASITCSGDGLSKKYVSWYQQKAGQSPVVLIS
RDKERPSGIPDRFSGSNSADTATLTISGTQAMDEADYYCQAWDDTTVVEGG
GTKLTVLTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFAC
DIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEED
GCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVL
DKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGH
DGLYQGLSTATKDTYDALHMQALPPR
149366-nt905ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCCAAGTGCAGCTGGTGCAGAGCGGGGCCGAAGTCAAGAAG
CCGGGAGCCTCCGTGAAAGTGTCCTGCAAGCCTTCGGGATACACCGTGACC
TCCCACTACATTCATTGGGTCCGCCGCGCCCCCGGCCAAGGACTCGAGTGG
ATGGGCATGATCAACCCTAGCGGCGGAGTGACCGCGTACAGCCAGACGCTG
CAGGGACGCGTGACTATGACCTCGGATACCTCCTCCTCCACCGTCTATATG
GAACTGTCCAGCCTGCGGTCCGAGGATACCGCCATGTACTACTGCGCCCGG
GAAGGATCAGGCTCCGGGTGGTATTTCGACTTCTGGGGAAGAGGCACCCTC
GTGACTGTGTCATCTGGGGGAGGGGGTTCCGGTGGTGGCGGATCGGGAGGA
GGCGGTTCATCCTACGTGCTGACCCAGCCACCCTCCGTGTCCGTGAGCCCC
GGCCAGACTGCATCGATTACATGTAGCGGCGACGGCCTCTCCAAGAAATAC
GTGTCGTGGTACCAGCAGAAGGCCGGACAGAGCCCGGTGGTGCTGATCTCA
AGAGATAAGGAGCGGCCTAGCGGAATCCCGGACAGGTTCTCGGGTTCCAAC
TCCGCGGACACTGCTACTCTGACCATCTCGGGGACCCAGGCTATGGACGAA
GCCGATTACTACTGCCAAGCCTGGGACGACACTACTGTCGTGTTTGGAGGG
GGCACCAAGTTGACCGTCCTTACCACTACCCCAGCACCGAGGCCACCCACC
CCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGT
AGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTCGCCTGC
GATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTT
TCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTAC
ATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGAC
GGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGC
GTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAAC
CAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTG
GACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAG
AATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAA
GCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAAGGCCAC
GACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCT
CTTCACATGCAGGCCCTGCCGCCTCGG
149367
149367-aa884MALPVTALLLPLALLLHAARPQVQLQESGPGLVKPSQTLSLTCTVSGGSIS
Full CARSGGYYWSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVTISVDTSKNQFS
LKLSSVTAADTAVYYCARAGIAARLRGAFDIWGQGTMVTVSSGGGGSGGGG
SGGGGSDIVMTQSPSSVSASVGDRVIITCRASQGIRNWLAWYQQKPGKAPN
LLIYAASNLQSGVPSRFSGSGSGADFTLTISSLQPEDVATYYCQKYNSAPF
TFGPGTKVDIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGL
DFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTT
QEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREE
YDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRR
GKGHDGLYQGLSTATKDTYDALHMQALPPR
149367-nt906ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCCAAGTGCAGCTTCAGGAGAGCGGCCCGGGACTCGTGAAG
CCGTCCCAGACCCTGTCCCTGACTTGCACCGTGTCGGGAGGAAGCATCTCG
AGCGGAGGCTACTATTGGTCGTGGATTCGGCAGCACCCTGGAAAGGGCCTG
GAATGGATCGGCTACATCTACTACTCCGGCTCGACCTACTACAACCCATCG
CTGAAGTCCAGAGTGACAATCTCAGTGGACACGTCCAAGAATCAGTTCAGC
CTGAAGCTCTCTTCCGTGACTGCGGCCGACACCGCCGTGTACTACTGCGCA
CGCGCTGGAATTGCCGCCCGGCTGAGGGGTGCCTTCGACATTTGGGGACAG
GGCACCATGGTCACCGTGTCCTCCGGCGGCGGAGGTTCCGGGGGTGGAGGC
TCAGGAGGAGGGGGGTCCGACATCGTCATGACTCAGTCGCCCTCAAGCGTC
AGCGCGTCCGTCGGGGACAGAGTGATCATCACCTGTCGGGCGTCCCAGGGA
ATTCGCAACTGGCTGGCCTGGTATCAGCAGAAGCCCGGAAAGGCCCCCAAC
CTGTTGATCTACGCCGCCTCAAACCTCCAATCCGGGGTGCCGAGCCGCTTC
AGCGGCTCCGGTTCGGGTGCCGATTTCACTCTGACCATCTCCTCCCTGCAA
CCTGAAGATGTGGCTACCTACTACTGCCAAAAGTACAACTCCGCACCTTTT
ACTTTCGGACCGGGGACCAAAGTGGACATTAAGACCACTACCCCAGCACCG
AGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGT
CCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTT
GACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGG
GTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAG
AAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACT
CAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGC
TGCGAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAG
CAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAG
TACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAG
CCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGAT
AAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGA
GGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGAC
ACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
149368
149368-aa885MALPVTALLLPLALLLHAARPQVQLVQSGAEVKKPGSSVKVSCKASGGTFS
Full CARSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYM
ELSSLRSEDTAVYYCARRGGYQLLRWDVGLLRSAFDIWGQGTMVTVSSGGG
GSGGGGSGGGGSSYVLTQPPSVSVAPGQTARITCGGNNIGSKSVHWYQQKP
GQAPVLVLYGKNNRPSGVPDRFSGSRSGTTASLTITGAQAEDEADYYCSSR
DSSGDHLRVFGTGTKVTVLTTTPAPRPPTPAPTIASQPLSLRPEACRPAAG
GAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP
FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNE
LNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEI
GMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR
149368-nt907ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCCAAGTGCAGCTGGTCCAGTCGGGCGCCGAGGTCAAGAAG
CCCGGGAGCTCTGTGAAAGTGTCCTGCAAGGCCTCCGGGGGCACCTTTAGC
TCCTACGCCATCTCCTGGGTCCGCCAAGCACCGGGTCAAGGCCTGGAGTGG
ATGGGGGGAATTATCCCTATCTTCGGCACTGCCAACTACGCCCAGAAGTTC
CAGGGACGCGTGACCATTACCGCGGACGAATCCACCTCCACCGCTTATATG
GAGCTGTCCAGCTTGCGCTCGGAAGATACCGCCGTGTACTACTGCGCCCGG
AGGGGTGGATACCAGCTGCTGAGATGGGACGTGGGCCTCCTGCGGTCGGCG
TTCGACATCTGGGGCCAGGGCACTATGGTCACTGTGTCCAGCGGAGGAGGC
GGATCGGGAGGCGGCGGATCAGGGGGAGGCGGTTCCAGCTACGTGCTTACT
CAACCCCCTTCGGTGTCCGTGGCCCCGGGACAGACCGCCAGAATCACTTGC
GGAGGAAACAACATTGGGTCCAAGAGCGTGCATTGGTACCAGCAGAAGCCA
GGACAGGCCCCTGTGCTGGTGCTCTACGGGAAGAACAATCGGCCCAGCGGA
GTGCCGGACAGGTTCTCGGGTTCACGCTCCGGTACAACCGCTTCACTGACT
ATCACCGGGGCCCAGGCAGAGGATGAAGCGGACTACTACTGTTCCTCCCGG
GATTCATCCGGCGACCACCTCCGGGTGTTCGGAACCGGAACGAAGGTCACC
GTGCTGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATC
GCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGT
GGGGCCGTGCATACCCGGGGTCTTGACTTCGCCTGCGATATCTACATTTGG
GCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACT
CTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTAAGCAACCC
TTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGG
TTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGCGTGAAATTCAGCCGC
AGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAA
CTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGA
CGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGC
CTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATT
GGTATGAAAGGGGAACGCAGAAGAGGCAAAGGCCACGACGGACTGTACCAG
GGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCC
CTGCCGCCTCGG
149369
149369-aa886MALPVTALLLPLALLLHAARPEVQLQQSGPGLVKPSQTLSLTCAISGDSVS
Full CARSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYSFYAISLKSRIIINPDTSKNQ
FSLQLKSVTPEDTAVYYCARSSPEGLFLYWFDPWGQGTLVTVSSGGDGSGG
GGSGGGGSSSELTQDPAVSVALGQTIRITCQGDSLGNYYATWYQQKPGQAP
VLVIYGTNNRPSGIPDRFSASSSGNTASLTITGAQAEDEADYYCNSRDSSG
HHLLFGTGTKVTVLTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHT
RGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPV
QTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGR
REEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE
RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR
149369-nt908ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
Full CARGCCGCTCGGCCCGAAGTGCAGCTCCAACAGTCAGGACCGGGGCTCGTGAAG
CCATCCCAGACCCTGTCCCTGACTTGTGCCATCTCGGGAGATAGCGTGTCA
TCGAACTCCGCCGCCTGGAACTGGATTCGGCAGAGCCCGTCCCGCGGACTG
GAGTGGCTTGGAAGGACCTACTACCGGTCCAAGTGGTACTCTTTCTACGCG
ATCTCGCTGAAGTCCCGCATTATCATTAACCCTGATACCTCCAAGAATCAG
TTCTCCCTCCAACTGAAATCCGTCACCCCCGAGGACACAGCAGTGTATTAC
TGCGCACGGAGCAGCCCCGAAGGACTGTTCCTGTATTGGTTTGACCCCTGG
GGCCAGGGGACTCTTGTGACCGTGTCGAGCGGCGGAGATGGGTCCGGTGGC
GGTGGTTCGGGGGGCGGCGGATCATCATCCGAACTGACCCAGGACCCGGCT
GTGTCCGTGGCGCTGGGACAAACCATCCGCATTACGTGCCAGGGAGACTCC
CTGGGCAACTACTACGCCACTTGGTACCAGCAGAAGCCGGGCCAAGCCCCT
GTGTTGGTCATCTACGGGACCAACAACAGACCTTCCGGCATCCCCGACCGG
TTCAGCGCTTCGTCCTCCGGCAACACTGCCAGCCTGACCATCACTGGAGCG
CAGGCCGAAGATGAGGCCGACTACTACTGCAACAGCAGAGACTCCTCGGGT
CATCACCTCTTGTTCGGAACTGGAACCAAGGTCACCGTGCTGACCACTACC
CCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTG
TCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACC
CGGGGTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGT
ACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGC
GGTCGGAAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTG
CAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAG
GAAGGCGGCTGCGAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCA
GCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGG
AGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATG
GGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTC
CAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAA
CGCAGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCC
ACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
BCMA_EBB-C1978-A4
BCMA_EBB-887MALPVTALLLPLALLLHAARPEVQLVESGGGLVQPGGSLRLSCAASGFTFS
C1978-A4-SYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYL
aaQMNSLRAEDTAVYYCAKVEGSGSLDYWGQGTLVTVSSGGGGSGGGGSGGGG
Full CARSEIVMTQSPGTLSLSPGERATLSCRASQSVSSAYLAWYQQKPGQPPRLLIS
GASTRATGIPDRFGGSGSGTDFTLTISRLEPEDFAVYYCQHYGSSFNGSSL
FTFGQGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRG
LDFACDTYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQT
TQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRRE
EYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR
RGKGHDGLYQGLSTATKDTYDALHMQALPPR
BCMA_EBB-909ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
C1978-A4-GCCGCTCGGCCCGAAGTGCAGCTCGTGGAGTCAGGAGGCGGCCTGGTCCAG
ntCCGGGAGGGTCCCTTAGACTGTCATGCGCCGCAAGCGGATTCACTTTCTCC
Full CARTCCTATGCCATGAGCTGGGTCCGCCAAGCCCCCGGAAAGGGACTGGAATGG
GTGTCCGCCATCTCGGGGTCTGGAGGCTCAACTTACTACGCTGACTCCGTG
AAGGGACGGTTCACCATTAGCCGCGACAACTCCAAGAACACCCTCTACCTC
CAAATGAACTCCCTGCGGGCCGAGGATACCGCCGTCTACTACTGCGCCAAA
GTGGAAGGTTCAGGATCGCTGGACTACTGGGGACAGGGTACTCTCGTGACC
GTGTCATCGGGCGGAGGAGGTTCCGGCGGTGGCGGCTCCGGCGGCGGAGGG
TCGGAGATCGTGATGACCCAGAGCCCTGGTACTCTGAGCCTTTCGCCGGGA
GAAAGGGCCACCCTGTCCTGCCGCGCTTCCCAATCCGTGTCCTCCGCGTAC
TTGGCGTGGTACCAGCAGAAGCCGGGACAGCCCCCTCGGCTGCTGATCAGC
GGGGCCAGCACCCGGGCAACCGGAATCCCAGACAGATTCGGGGGTTCCGGC
AGCGGCACAGATTTCACCCTGACTATTTCGAGGTTGGAGCCCGAGGACTTT
GCGGTGTATTACTGTCAGCACTACGGGTCGTCCTTTAATGGCTCCAGCCTG
TTCACGTTCGGACAGGGGACCCGCCTGGAAATCAAGACCACTACCCCAGCA
CCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTG
CGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGT
CTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGC
GGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGG
AAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACT
ACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGC
GGCTGCGAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTAC
AAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAG
GAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGG
AAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAG
GATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGA
AGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAG
GACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
BCMA_EBB-C1978-G1
BCMA_EBB-888MALPVTALLLPLALLLHAARPEVQLVETGGGLVQPGGSLRLSCAASGITFS
C1978-G1-RYPMSWVRQAPGKGLEWVSGISDSGVSTYYADSAKGRFTISRDNSKNTLFL
aaQMSSLRDEDTAVYYCVTRAGSEASDIWGQGTMVTVSSGGGGSGGGGSGGGG
Full CARSEIVLTQSPATLSLSPGERATLSCRASQSVSNSLAWYQQKPGQAPRLLIYD
ASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAIYYCQQFGTSSGLTEGG
GTKLEIKITTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFAC
DIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEED
GCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVL
DKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGH
DGLYQGLSTATKDTYDALHMQALPPR
BCMA_EBB-910ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
C1978-G1-GCCGCTCGGCCCGAAGTGCAACTGGTGGAAACCGGTGGCGGCCTGGTGCAG
ntCCTGGAGGATCATTGAGGCTGTCATGCGCGGCCAGCGGTATTACCTTCTCC
Full CARCGGTACCCCATGTCCTGGGTCAGACAGGCCCCGGGGAAAGGGCTTGAATGG
GTGTCCGGGATCTCGGACTCCGGTGTCAGCACTTACTACGCCGACTCCGCC
AAGGGACGCTTCACCATTTCCCGGGACAACTCGAAGAACACCCTGTTCCTC
CAAATGAGCTCCCTCCGGGACGAGGATACTGCAGTGTACTACTGCGTGACC
CGCGCCGGGTCCGAGGCGTCTGACATTTGGGGACAGGGCACTATGGTCACC
GTGTCGTCCGGCGGAGGGGGCTCGGGAGGCGGTGGCAGCGGAGGAGGAGGG
TCCGAGATCGTGCTGACCCAATCCCCGGCCACCCTCTCGCTGAGCCCTGGA
GAAAGGGCAACCTTGTCCTGTCGCGCGAGCCAGTCCGTGAGCAACTCCCTG
GCCTGGTACCAGCAGAAGCCCGGACAGGCTCCGAGACTTCTGATCTACGAC
GCTTCGAGCCGGGCCACTGGAATCCCCGACCGCTTTTCGGGGTCCGGCTCA
GGAACCGATTTCACCCTGACAATCTCACGGCTGGAGCCAGAGGATTTCGCC
ATCTATTACTGCCAGCAGTTCGGTACTTCCTCCGGCCTGACTTTCGGAGGC
GGCACGAAGCTCGAAATCAAGACCACTACCCCAGCACCGAGGCCACCCACC
CCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGT
AGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTCGCCTGC
GATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTT
TCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTAC
ATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGAC
GGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGC
GTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAAC
CAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTG
GACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAG
AATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAA
GCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAAGGCCAC
GACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCT
CTTCACATGCAGGCCCTGCCGCCTCGG
BCMA_EBB-C1979-C1
BCMA_EBB-889MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGGSLRLSCAASGFTFS
C1979-C1-SYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNAKNSLYL
aaQMNSLRAEDTAIYYCARATYKRELRYYYGMDVWGQGTMVTVSSGGGGSGGG
Full CARGSGGGGSEIVMTQSPGTVSLSPGERATLSCRASQSVSSSFLAWYQQKPGQA
PRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDSAVYYCQQYHSS
PSWTFGQGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHT
RGLDFACDTYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPV
QTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGR
REEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE
RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR
BCMA_EBB-911ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
C1979-C1-GCCGCTCGGCCCCAAGTGCAGCTCGTGGAATCGGGTGGCGGACTGGTGCAG
ntCCGGGGGGCTCACTTAGACTGTCCTGCGCGGCCAGCGGATTCACTTTCTCC
Full CARTCCTACGCCATGTCCTGGGTCAGACAGGCCCCTGGAAAGGGCCTGGAATGG
GTGTCCGCAATCAGCGGCAGCGGCGGCTCGACCTATTACGCGGATTCAGTG
AAGGGCAGATTCACCATTTCCCGGGACAACGCCAAGAACTCCTTGTACCTT
CAAATGAACTCCCTCCGCGCGGAAGATACCGCAATCTACTACTGCGCTCGG
GCCACTTACAAGAGGGAACTGCGCTACTACTACGGGATGGACGTCTGGGGC
CAGGGAACCATGGTCACCGTGTCCAGCGGAGGAGGAGGATCGGGAGGAGGC
GGTAGCGGGGGTGGAGGGTCGGAGATCGTGATGACCCAGTCCCCCGGCACT
GTGTCGCTGTCCCCCGGCGAACGGGCCACCCTGTCATGTCGGGCCAGCCAG
TCAGTGTCGTCAAGCTTCCTCGCCTGGTACCAGCAGAAACCGGGACAAGCT
CCCCGCCTGCTGATCTACGGAGCCAGCAGCCGGGCCACCGGTATTCCTGAC
CGGTTCTCCGGTTCGGGGTCCGGGACCGACTTTACTCTGACTATCTCTCGC
CTCGAGCCAGAGGACTCCGCCGTGTATTACTGCCAGCAGTACCACTCCTCC
CCGTCCTGGACGTTCGGACAGGGCACAAGGCTGGAGATTAAGACCACTACC
CCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTG
TCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACC
CGGGGTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGT
ACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGC
GGTCGGAAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTG
CAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAG
GAAGGCGGCTGCGAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCA
GCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGG
AGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATG
GGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTC
CAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAA
CGCAGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCC
ACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
BCMA_EBB-C1978-C7
BCMA_EBB-890MALPVTALLLPLALLLHAARPEVQLVETGGGLVQPGGSLRLSCAASGFTFS
C1978-C7-SYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYL
aaQMNTLKAEDTAVYYCARATYKRELRYYYGMDVWGQGTTVTVSSGGGGSGGG
Full CARGSGGGGSEIVLTQSPSTLSLSPGESAILSCRASQSVSTTFLAWYQQKPGQA
PRLLIYGSSNRATGIPDRFSGSGSGTDFTLTIRRLEPEDFAVYYCQQYHSS
PSWTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHT
RGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPV
QTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGR
REEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE
RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR
BCMA_EBB-912ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
C1978-C7-GCCGCTCGGCCCGAGGTGCAGCTTGTGGAAACCGGTGGCGGACTGGTGCAG
ntCCCGGAGGAAGCCTCAGGCTGTCCTGCGCCGCGTCCGGCTTCACCTTCTCC
Full CARTCGTACGCCATGTCCTGGGTCCGCCAGGCCCCCGGAAAGGGCCTGGAATGG
GTGTCCGCCATCTCTGGAAGCGGAGGTTCCACGTACTACGCGGACAGCGTC
AAGGGAAGGTTCACAATCTCCCGCGATAATTCGAAGAACACTCTGTACCTT
CAAATGAACACCCTGAAGGCCGAGGACACTGCTGTGTACTACTGCGCACGG
GCCACCTACAAGAGAGAGCTCCGGTACTACTACGGAATGGACGTCTGGGGC
CAGGGAACTACTGTGACCGTGTCCTCGGGAGGGGGTGGCTCCGGGGGGGGC
GGCTCCGGCGGAGGCGGTTCCGAGATTGTGCTGACCCAGTCACCTTCAACT
CTGTCGCTGTCCCCGGGAGAGAGCGCTACTCTGAGCTGCCGGGCCAGCCAG
TCCGTGTCCACCACCTTCCTCGCCTGGTATCAGCAGAAGCCGGGGCAGGCA
CCACGGCTCTTGATCTACGGGTCAAGCAACAGAGCGACCGGAATTCCTGAC
CGCTTCTCGGGGAGCGGTTCAGGCACCGACTTCACCCTGACTATCCGGCGC
CTGGAACCCGAAGATTTCGCCGTGTATTACTGTCAACAGTACCACTCCTCG
CCGTCCTGGACCTTTGGCCAAGGAACCAAAGTGGAAATCAAGACCACTACC
CCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTG
TCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACC
CGGGGTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGT
ACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGC
GGTCGGAAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTG
CAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAG
GAAGGCGGCTGCGAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCA
GCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGG
AGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATG
GGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTC
CAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAA
CGCAGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCC
ACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
BCMA_EBB-C1978-D10
BCMA_EBB-891MALPVTALLLPLALLLHAARPEVQLVETGGGLVQPGRSLRLSCAASGFTFD
C1978-D10-DYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYL
aaQMNSLRDEDTAVYYCARVGKAVPDVWGQGTTVTVSSGGGGSGGGGSGGGGS
Full CARDIVMTQTPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAA
SSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYSFGQGT
RLEIKITTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDI
YIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGC
SCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDK
RRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDG
LYQGLSTATKDTYDALHMQALPPR
BCMA_EBB-913ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
C1978-D10-GCCGCTCGGCCCGAAGTGCAGCTCGTGGAAACTGGAGGTGGACTCGTGCAG
ntCCTGGACGGTCGCTGCGGCTGAGCTGCGCTGCATCCGGCTTCACCTTCGAC
Full CARGATTATGCCATGCACTGGGTCAGACAGGCGCCAGGGAAGGGACTTGAGTGG
GTGTCCGGTATCAGCTGGAATAGCGGCTCAATCGGATACGCGGACTCCGTG
AAGGGAAGGTTCACCATTTCCCGCGACAACGCCAAGAACTCCCTGTACTTG
CAAATGAACAGCCTCCGGGATGAGGACACTGCCGTGTACTACTGCGCCCGC
GTCGGAAAAGCTGTGCCCGACGTCTGGGGCCAGGGAACCACTGTGACCGTG
TCCAGCGGCGGGGGTGGATCGGGCGGTGGAGGGTCCGGTGGAGGGGGCTCA
GATATTGTGATGACCCAGACCCCCTCGTCCCTGTCCGCCTCGGTCGGCGAC
CGCGTGACTATCACATGTAGAGCCTCGCAGAGCATCTCCAGCTACCTGAAC
TGGTATCAGCAGAAGCCGGGGAAGGCCCCGAAGCTCCTGATCTACGCGGCA
TCATCACTGCAATCGGGAGTGCCGAGCCGGTTTTCCGGGTCCGGCTCCGGC
ACCGACTTCACGCTGACCATTTCTTCCCTGCAACCCGAGGACTTCGCCACT
TACTACTGCCAGCAGTCCTACTCCACCCCTTACTCCTTCGGCCAAGGAACC
AGGCTGGAAATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCT
CCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCC
GCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTCGCCTGCGATATC
TACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTC
GTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTT
AAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGT
TCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGCGTGAAA
TTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTC
TACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAG
CGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCC
CAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTAT
AGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAAGGCCACGACGGA
CTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCAC
ATGCAGGCCCTGCCGCCTCGG
BCMA_EBB-C1979-C12
BCMA_EBB-892MALPVTALLLPLALLLHAARPEVQLVESGGGLVQPGRSLRLSCTASGFTFD
C1979-C12-DYAMHWVRQRPGKGLEWVASINWKGNSLAYGDSVKGRFAISRDNAKNTVEL
aaQMNSLRTEDTAVYYCASHQGVAYYNYAMDVWGRGTLVTVSSGGGGSGGGGS
Full CARGGGGSEIVLTQSPGTLSLSPGERATLSCRATQSIGSSFLAWYQQRPGQAPR
LLIYGASQRATGIPDRFSGRGSGTDFTLTISRVEPEDSAVYYCQHYESSPS
WTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRG
LDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQT
TQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRRE
EYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR
RGKGHDGLYQGLSTATKDTYDALHMQALPPR
BCMA_EBB-914ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
C1979-C12-GCCGCTCGGCCCGAAGTGCAGCTCGTGGAGAGCGGGGGAGGATTGGTGCAG
ntCCCGGAAGGTCCCTGCGGCTCTCCTGCACTGCGTCTGGCTTCACCTTCGAC
Full CARGACTACGCGATGCACTGGGTCAGACAGCGCCCGGGAAAGGGCCTGGAATGG
GTCGCCTCAATCAACTGGAAGGGAAACTCCCTGGCCTATGGCGACAGCGTG
AAGGGCCGCTTCGCCATTTCGCGCGACAACGCCAAGAACACCGTGTTTCTG
CAAATGAATTCCCTGCGGACCGAGGATACCGCTGTGTACTACTGCGCCAGC
CACCAGGGCGTGGCATACTATAACTACGCCATGGACGTGTGGGGAAGAGGG
ACGCTCGTCACCGTGTCCTCCGGGGGCGGTGGATCGGGTGGAGGAGGAAGC
GGTGGCGGGGGCAGCGAAATCGTGCTGACTCAGAGCCCGGGAACTCTTTCA
CTGTCCCCGGGAGAACGGGCCACTCTCTCGTGCCGGGCCACCCAGTCCATC
GGCTCCTCCTTCCTTGCCTGGTACCAGCAGAGGCCAGGACAGGCGCCCCGC
CTGCTGATCTACGGTGCTTCCCAACGCGCCACTGGCATTCCTGACCGGTTC
AGCGGCAGAGGGTCGGGAACCGATTTCACACTGACCATTTCCCGGGTGGAG
CCCGAAGATTCGGCAGTCTACTACTGTCAGCATTACGAGTCCTCCCCTTCA
TGGACCTTCGGTCAAGGGACCAAAGTGGAGATCAAGACCACTACCCCAGCA
CCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTG
CGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGT
CTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGC
GGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGG
AAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACT
ACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGC
GGCTGCGAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTAC
AAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAG
GAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGG
AAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAG
GATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGA
AGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAG
GACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
BCMA_EBB-C1980-G4
BCMA_EBB-893MALPVTALLLPLALLLHAARPEVQLVESGGGLVQPGGSLRLSCAASGFTFS
C1980-G4-SYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYL
aaQMNSLRAEDTAVYYCAKVVRDGMDVWGQGTTVTVSSGGGGSGGGGSGGGGS
Full CAREIVLTQSPATLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYG
ASSRATGIPDRFSGNGSGTDFTLTISRLEPEDFAVYYCQQYGSPPRFTFGP
GTKVDIKITTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFAC
DIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEED
GCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVL
DKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGH
DGLYQGLSTATKDTYDALHMQALPPR
BCMA_EBB-915ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
C1980-G4-GCCGCTCGGCCCGAGGTGCAGTTGGTCGAAAGCGGGGGCGGGCTTGTGCAG
ntCCTGGCGGATCACTGCGGCTGTCCTGCGCGGCATCAGGCTTCACGTTTTCT
Full CARTCCTACGCCATGTCCTGGGTGCGCCAGGCCCCTGGAAAGGGACTGGAATGG
GTGTCCGCGATTTCGGGGTCCGGCGGGAGCACCTACTACGCCGATTCCGTG
AAGGGCCGCTTCACTATCTCGCGGGACAACTCCAAGAACACCCTCTACCTC
CAAATGAATAGCCTGCGGGCCGAGGATACCGCCGTCTACTATTGCGCTAAG
GTCGTGCGCGACGGAATGGACGTGTGGGGACAGGGTACCACCGTGACAGTG
TCCTCGGGGGGAGGCGGTAGCGGCGGAGGAGGAAGCGGTGGTGGAGGTTCC
GAGATTGTGCTGACTCAATCACCCGCGACCCTGAGCCTGTCCCCCGGCGAA
AGGGCCACTCTGTCCTGTCGGGCCAGCCAATCAGTCTCCTCCTCGTACCTG
GCCTGGTACCAGCAGAAGCCAGGACAGGCTCCGAGACTCCTTATCTATGGC
GCATCCTCCCGCGCCACCGGAATCCCGGATAGGTTCTCGGGAAACGGATCG
GGGACCGACTTCACTCTCACCATCTCCCGGCTGGAACCGGAGGACTTCGCC
GTGTACTACTGCCAGCAGTACGGCAGCCCGCCTAGATTCACTTTCGGCCCC
GGCACCAAAGTGGACATCAAGACCACTACCCCAGCACCGAGGCCACCCACC
CCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGT
AGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTCGCCTGC
GATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTT
TCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTAC
ATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGAC
GGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGC
GTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAAC
CAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTG
GACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAG
AATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAA
GCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAAGGCCAC
GACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCT
CTTCACATGCAGGCCCTGCCGCCTCGG
BCMA_EBB-C1980-D2
BCMA_EBB-894MALPVTALLLPLALLLHAARPEVQLLESGGGLVQPGGSLRLSCAASGFTFS
C1980-D2-SYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYL
aaQMNSLRAEDTAVYYCAKIPQTGTFDYWGQGTLVTVSSGGGGSGGGGSGGGG
Full CARSEIVLTQSPGILSLSPGERATLSCRASQSVSSSYLAWYQQRPGQAPRLLIY
GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGSSPSWTFG
QGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFA
CDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEE
DGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDV
LDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKG
HDGLYQGLSTATKDTYDALHMQALPPR
BCMA_EBB-916ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
C1980-D2-GCCGCTCGGCCCGAAGTGCAGCTGCTGGAGTCCGGCGGTGGATTGGTGCAA
ntCCGGGGGGATCGCTCAGACTGTCCTGTGCGGCGTCAGGCTTCACCTTCTCG
Full CARAGCTACGCCATGTCATGGGTCAGACAGGCCCCTGGAAAGGGTCTGGAATGG
GTGTCCGCCATTTCCGGGAGCGGGGGATCTACATACTACGCCGATAGCGTG
AAGGGCCGCTTCACCATTTCCCGGGACAACTCCAAGAACACTCTCTATCTG
CAAATGAACTCCCTCCGCGCTGAGGACACTGCCGTGTACTACTGCGCCAAA
ATCCCTCAGACCGGCACCTTCGACTACTGGGGACAGGGGACTCTGGTCACC
GTCAGCAGCGGTGGCGGAGGTTCGGGGGGAGGAGGAAGCGGCGGCGGAGGG
TCCGAGATTGTGCTGACCCAGTCACCCGGCACTTTGTCCCTGTCGCCTGGA
GAAAGGGCCACCCTTTCCTGCCGGGCATCCCAATCCGTGTCCTCCTCGTAC
CTGGCCTGGTACCAGCAGAGGCCCGGACAGGCCCCACGGCTTCTGATCTAC
GGAGCAAGCAGCCGCGCGACCGGTATCCCGGACCGGTTTTCGGGCTCGGGC
TCAGGAACTGACTTCACCCTCACCATCTCCCGCCTGGAACCCGAAGATTTC
GCTGTGTATTACTGCCAGCACTACGGCAGCTCCCCGTCCTGGACGTTCGGC
CAGGGAACTCGGCTGGAGATCAAGACCACTACCCCAGCACCGAGGCCACCC
ACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCA
TGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTCGCC
TGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTG
CTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTG
TACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAG
GACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTG
CGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAG
AACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTG
CTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGA
AAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCA
GAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAAGGC
CACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGAC
GCTCTTCACATGCAGGCCCTGCCGCCTCGG
BCMA_EBB-C1978-A10
BCMA_EBB-895MALPVTALLLPLALLLHAARPEVQLVETGGGLVQPGGSLRLSCAASGFTFS
C1978-A10-SYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTMSRENDKNSVFL
aaQMNSLRVEDTGVYYCARANYKRELRYYYGMDVWGQGTMVTVSSGGGGSGGG
Full CARGSGGGGSEIVMTQSPGTLSLSPGESATLSCRASQRVASNYLAWYQHKPGQA
PSLLISGASSRATGVPDRFSGSGSGTDFTLAISRLEPEDSAVYYCQHYDSS
PSWTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHT
RGLDFACDTYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPV
QTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGR
REEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE
RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR
BCMA_EBB-917ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
C1978-A10-GCCGCTCGGCCCGAAGTGCAACTGGTGGAAACCGGTGGAGGACTCGTGCAG
ntCCTGGCGGCAGCCTCCGGCTGAGCTGCGCCGCTTCGGGATTCACCTTTTCC
Full CARTCCTACGCGATGTCTTGGGTCAGACAGGCCCCCGGAAAGGGGCTGGAATGG
GTGTCAGCCATCTCCGGCTCCGGCGGATCAACGTACTACGCCGACTCCGTG
AAAGGCCGGTTCACCATGTCGCGCGAGAATGACAAGAACTCCGTGTTCCTG
CAAATGAACTCCCTGAGGGTGGAGGACACCGGAGTGTACTATTGTGCGCGC
GCCAACTACAAGAGAGAGCTGCGGTACTACTACGGAATGGACGTCTGGGGA
CAGGGAACTATGGTGACCGTGTCATCCGGTGGAGGGGGAAGCGGCGGTGGA
GGCAGCGGGGGCGGGGGTTCAGAAATTGTCATGACCCAGTCCCCGGGAACT
CTTTCCCTCTCCCCCGGGGAATCCGCGACTTTGTCCTGCCGGGCCAGCCAG
CGCGTGGCCTCGAACTACCTCGCATGGTACCAGCATAAGCCAGGCCAAGCC
CCTTCCCTGCTGATTTCCGGGGCTAGCAGCCGCGCCACTGGCGTGCCGGAT
AGGTTCTCGGGAAGCGGCTCGGGTACCGATTTCACCCTGGCAATCTCGCGG
CTGGAACCGGAGGATTCGGCCGTGTACTACTGCCAGCACTATGACTCATCC
CCCTCCTGGACATTCGGACAGGGCACCAAGGTCGAGATCAAGACCACTACC
CCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTG
TCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACC
CGGGGTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGT
ACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGC
GGTCGGAAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTG
CAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAG
GAAGGCGGCTGCGAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCA
GCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGG
AGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATG
GGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTC
CAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAA
CGCAGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCC
ACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
BCMA_EBB-C1978-D4
BCMA_EBB-896MALPVTALLLPLALLLHAARPEVQLLETGGGLVQPGGSLRLSCAASGFSFS
C1978-D4-SYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYL
aaQMNSLRAEDTAVYYCAKALVGATGAFDIWGQGTLVTVSSGGGGSGGGGSGG
Full CARGGSEIVLTQSPGTLSLSPGERATLSCRASQSLSSNFLAWYQQKPGQAPGLL
IYGASNWATGTPDRFSGSGSGTDFTLTITRLEPEDFAVYYCQYYGTSPMYT
FGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLD
FACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQ
EEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEY
DVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRG
KGHDGLYQGLSTATKDTYDALHMQALPPR
BCMA_EBB-918ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
C1978-D4-GCCGCTCGGCCCGAAGTGCAGCTGCTCGAAACCGGTGGAGGGCTGGTGCAG
ntCCAGGGGGCTCCCTGAGGCTTTCATGCGCCGCTAGCGGATTCTCCTTCTCC
Full CARTCTTACGCCATGTCGTGGGTCCGCCAAGCCCCTGGAAAAGGCCTGGAATGG
GTGTCCGCGATTTCCGGGAGCGGAGGTTCGACCTATTACGCCGACTCCGTG
AAGGGCCGCTTTACCATCTCCCGGGATAACTCCAAGAACACTCTGTACCTC
CAAATGAACTCGCTGAGAGCCGAGGACACCGCCGTGTATTACTGCGCGAAG
GCGCTGGTCGGCGCGACTGGGGCATTCGACATCTGGGGACAGGGAACTCTT
GTGACCGTGTCGAGCGGAGGCGGCGGCTCCGGCGGAGGAGGGAGCGGGGGC
GGTGGTTCCGAAATCGTGTTGACTCAGTCCCCGGGAACCCTGAGCTTGTCA
CCCGGGGAGCGGGCCACTCTCTCCTGTCGCGCCTCCCAATCGCTCTCATCC
AATTTCCTGGCCTGGTACCAGCAGAAGCCCGGACAGGCCCCGGGCCTGCTC
ATCTACGGCGCTTCAAACTGGGCAACGGGAACCCCTGATCGGTTCAGCGGA
AGCGGATCGGGTACTGACTTTACCCTGACCATCACCAGACTGGAACCGGAG
GACTTCGCCGTGTACTACTGCCAGTACTACGGCACCTCCCCCATGTACACA
TTCGGACAGGGTACCAAGGTCGAGATTAAGACCACTACCCCAGCACCGAGG
CCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCG
GAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTTTGAC
TTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTC
CTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAG
CTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAA
GAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGC
GAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAG
GGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTAC
GACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCG
CGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAG
ATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGC
AAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACC
TATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
BCMA_EBB-C1980-A2
BCMA_EBB-897MALPVTALLLPLALLLHAARPEVQLLESGGGLVQPGGSLRLSCAASGFTFS
C1980-A2-SYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYL
aaQMNSLRAEDTAVYYCVLWFGEGFDPWGQGTLVTVSSGGGGSGGGGSGGGGS
Full CARDIVLTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQL
LIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLT
FGGGTKVDIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLD
FACDTYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQ
EEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEY
DVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRG
KGHDGLYQGLSTATKDTYDALHMQALPPR
BCMA_EBB-919ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
C1980-A2-GCCGCTCGGCCCGAAGTGCAGCTGCTTGAGAGCGGTGGAGGTCTGGTGCAG
ntCCCGGGGGATCACTGCGCCTGTCCTGTGCCGCGTCCGGTTTCACTTTCTCC
Full CARTCGTACGCCATGTCGTGGGTCAGACAGGCACCGGGAAAGGGACTGGAATGG
GTGTCAGCCATTTCGGGTTCGGGGGGCAGCACCTACTACGCTGACTCCGTG
AAGGGCCGGTTCACCATTTCCCGCGACAACTCCAAGAACACCTTGTACCTC
CAAATGAACTCCCTGCGGGCCGAAGATACCGCCGTGTATTACTGCGTCTG
TGGTTCGGAGAGGGATTCGACCCGTGGGGACAAGGAACACTCGTGACTGTG
TCATCCGGCGGAGGCGGCAGCGGTGGCGGCGGTTCCGGCGGCGGCGGATCT
GACATCGTGTTGACCCAGTCCCCTCTGAGCCTGCCGGTCACTCCTGGCGAA
CCAGCCAGCATCTCCTGCCGGTCGAGCCAGTCCCTCCTGCACTCCAATGGG
TACAACTACCTCGATTGGTATCTGCAAAAGCCGGGCCAGAGCCCCCAGCTG
CTGATCTACCTTGGGTCAAACCGCGCTTCCGGGGTGCCTGATAGATTCTCC
GGGTCCGGGAGCGGAACCGACTTTACCCTGAAAATCTCGAGGGTGGAGGCC
GAGGACGTCGGAGTGTACTACTGCATGCAGGCGCTCCAGACTCCCCTGACC
TTCGGAGGAGGAACGAAGGTCGACATCAAGACCACTACCCCAGCACCGAGG
CCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCG
GAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGAC
TTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTC
CTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAG
CTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAA
GAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGC
GAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAG
GGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTAC
GACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCG
CGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAG
ATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGC
AAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACC
TATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
BCMA_EBB-C1981-C3
BCMA_EBB-898MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGGSLRLSCAASGFTFS
C1981-C3-SYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYL
aaQMNSLRAEDTAVYYCAKVGYDSSGYYRDYYGMDVWGQGTTVTVSSGGGGSG
Full CARGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPG
QAPRLLIYGTSSRATGISDRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYG
NSPPKFTFGPGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGA
VHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFM
RPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELN
LGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGM
KGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR
BCMA_EBB-920ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
C1981-C3-GCCGCTCGGCCCCAAGTGCAGCTCGTGGAGTCAGGCGGAGGACTGGTGCAG
ntCCCGGGGGCTCCCTGAGACTTTCCTGCGCGGCATCGGGTTTTACCTTCTCC
Full CARTCCTATGCTATGTCCTGGGTGCGCCAGGCCCCGGGAAAGGGACTGGAATGG
GTGTCCGCAATCAGCGGTAGCGGGGGCTCAACATACTACGCCGACTCCGTC
AAGGGTCGCTTCACTATTTCCCGGGACAACTCCAAGAATACCCTGTACCTC
CAAATGAACAGCCTCAGGGCCGAGGATACTGCCGTGTACTACTGCGCCAAA
GTCGGATACGATAGCTCCGGTTACTACCGGGACTACTACGGAATGGACGTG
TGGGGACAGGGCACCACCGTGACCGTGTCAAGCGGCGGAGGCGGTTCAGGA
GGGGGAGGCTCCGGCGGTGGAGGGTCCGAAATCGTCCTGACTCAGTCGCCT
GGCACTCTGTCGTTGTCCCCGGGGGAGCGCGCTACCCTGTCGTGTCGGGCG
TCGCAGTCCGTGTCGAGCTCCTACCTCGCGTGGTACCAGCAGAAGCCCGGA
CAGGCCCCTAGACTTCTGATCTACGGCACTTCTTCACGCGCCACCGGGATC
AGCGACAGGTTCAGCGGCTCCGGCTCCGGGACCGACTTCACCCTGACCATT
AGCCGGCTGGAGCCTGAAGATTTCGCCGTGTATTACTGCCAACACTACGGA
AACTCGCCGCCAAAGTTCACGTTCGGACCCGGAACCAAGCTGGAAATCAAG
ACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCC
CAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCC
GTGCATACCCGGGGTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCCT
CTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTAC
TGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATG
AGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCA
GAGGAGGAGGAAGGCGGCTGCGAACTGCGCGTGAAATTCAGCCGCAGCGCA
GATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAAT
CTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGAC
CCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTAC
AACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATG
AAAGGGGAACGCAGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTC
AGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCG
CCTCGG
BCMA_EBB-C1978-G4
BCMA_EBB-899MALPVTALLLPLALLLHAARPEVQLVESGGGLVQPGGSLRLSCAASGFTFS
C1978-G4-SYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYL
aaQMNSLRAEDTAVYYCAKMGWSSGYLGAFDIWGQGTTVTVSSGGGGSGGGGS
Full CARGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVASSFLAWYQQKPGQAPR
LLIYGASGRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGGSPR
LTFGGGTKVDIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRG
LDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQT
TQEEDGCSCREPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRRE
EYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR
RGKGHDGLYQGLSTATKDTYDALHMQALPPR
BCMA_EBB-921ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCAC
C1978-G4-GCCGCTCGGCCCGAAGTCCAACTGGTGGAGTCCGGGGGAGGGCTCGTGCAG
ntCCCGGAGGCAGCCTTCGGCTGTCGTGCGCCGCCTCCGGGTTCACGTTCTCA
Full CARTCCTACGCGATGTCGTGGGTCAGACAGGCACCAGGAAAGGGACTGGAATGG
GTGTCCGCCATTAGCGGCTCCGGCGGTAGCACCTACTATGCCGACTCAGTG
AAGGGAAGGTTCACTATCTCCCGCGACAACAGCAAGAACACCCTGTACCTC
CAAATGAACTCTCTGCGGGCCGAGGATACCGCGGTGTACTATTGCGCCAAG
ATGGGTTGGTCCAGCGGATACTTGGGAGCCTTCGACATTTGGGGACAGGGC
ACTACTGTGACCGTGTCCTCCGGGGGTGGCGGATCGGGAGGCGGCGGCTCG
GGTGGAGGGGGTTCCGAAATCGTGTTGACCCAGTCACCGGGAACCCTCTCG
CTGTCCCCGGGAGAACGGGCTACACTGTCATGTAGAGCGTCCCAGTCCGTG
GCTTCCTCGTTCCTGGCCTGGTACCAGCAGAAGCCGGGACAGGCACCCCGC
CTGCTCATCTACGGAGCCAGCGGCCGGGCGACCGGCATCCCTGACCGCTTC
TCCGGTTCCGGCTCGGGCACCGACTTTACTCTGACCATTAGCAGGCTTGAG
CCCGAGGATTTTGCCGTGTACTACTGCCAACACTACGGGGGGAGCCCTCGC
CTGACCTTCGGAGGCGGAACTAAGGTCGATATCAAAACCACTACCCCAGCA
CCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTG
CGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGT
CTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGC
GGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGG
AAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACT
ACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGC
GGCTGCGAACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTAC
AAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAG
GAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGG
AAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAG
GATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGA
AGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAG
GACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG
TABLE 14 — Cas9 variants (NLS =SV40 NLS; Cas9 = S. Pyogenes Cas9 wild type, with any mutations indicated in parenthesis; Cas9e1.1 (as described in Slaymaker et al. 2015, Science 351: 84); GGS = glycine-glycine-serine).
CAS9Molar
(His6 disclosed as SEQ IDSizeConcconc.
iprotNO: 108)(Daltons)(ug/ml)[uM]
106520His6-GGS-NLS-CAS9-NLS161696.226.238.34
106518NLS-CAS9(C80L, C574E)-161531.046.540.24
NLS-His6
106521NLS-CAS9-His6160629.9637.12
106745NLS-CAS9(K855A)-NLS-161437.945.936.55
His6
106747NLS-CAS9e1.1-NLS-His6161295.746.540.3
106154NLS-CAS9-NLS-His6161495.045.936.54
(also
referred
to as
105026)
TABLE 16 — PCR amplicon
PrimerSequencelength (bp)
p15′-acacagccagaccatatcagcag739
(SEQ ID NO: 10518)
p25′-aaggcacgcaagggccataacc
(SEQ ID NO: 10519)
P35′-gaggcctgtgcagactactc1093
(SEQ ID NO: 10520)
p45′-acagaaatcctatgtggcctgc
(SEQ ID NO: 10521)
TABLE 17
Component50 μL reaction
ddH 2 O34.5 μL
5× Phusion HF buffer10 μL
10 mM dNTP1 μL
10 μM primer a1 μL
10 μM primer b1 μL
Cell lysate2 μL
Phusion DNA Polymerase0.5 μL
TABLE 18
Cycle stepTempTimeCycles
Initial denaturation98° C.30s1
Denaturation98° C.5s
Annealing68° C.20s35
Extension72° C.20s
Final extension72° C.1min
Final step14° C.Hold
TABLE 19
GuidegRNA targetingSEQ IDAverageSD
TargetIDCoordinateStranddomain sequenceNO:edit (%)(%)
Tet2CR00chr4: 105271340-+GAAGUAGUAAAU1019145.3%17.0%
7665105271360GAUAACUG
Tet2CR00chr4: 105270694-+UAUAUGUUCUAU1015342.9%27.0%
7697105270714ACCAACAA
Tet2CR00chr4: 105270624-+UGGAUCGGUCUU1014842.3%10.2%
7626105270643GUAAUUGG
Tet2CR00chr4: 105270350-−ACUGGUUUAGAU1025939.3%10.0%
7671105270370UAACACCA
Tet2CR00chr4: 105272182-−UGUGAAGCCUCU1031435.6%9.5%
7684105272202UCAAAAAC
Tet2CR00chr4: 105271863-+UUUCAGAGUACC1020627.1%6.3%
7633105271883CACUUAUA
Tet2CR00chr4: 105271203-−AGUUAGGAAACC1051526.8%6.7%
7677105271223AGAACCUA
Tet2CR00chr4: 105272465-+ACACAAAUCUGA1023426.7%14.2%
7691105272485AUACUGAG
Tet2CR00chr4: 105270695-+AUAUGUUCUAUA1015425.9%17.1%
7634105270715CCAACAAA
Tet2CR00chr4: 105272324-+GAUAGACUCAGA1022523.9%11.1%
7706105272344GAAAGGGU
Tet2CR00chr4: 105271526-+UAUGUAUGGGAA1020323.4%9.1%
7703105271546AAGUAACA
Tet2CR00chr4: 105270268-+AUAACUAGCACU1013620.7%14.2%
7675105270288CUCAUGAU
Tet2CR00chr4: 105270426-−AUUACAAUCUAC1026320.5%8.9%
7667105270446CAGGUAAC
Tet2CR00chr4: 105272320-+UCCUGAUAGACU1022320.3%17.2%
7680105272340CAGAGAAA
Tet2CR00chr4: 105270144-+CAUGUUGAGGAG1013120.0%7.0%
7655105270164CAGAACAC
Tet2CR00chr4: 105272436-+GUCACUGAUCUG1023319.3%5.5%
7632105272456GAUCAACU
Tet2CR00chr4: 105271924-+GGUUUGACAGAG1020918.6%9.2%
7648105271944UACAAAGG
Tet2CR00chr4: 105270594-+AGCCUGACUACA1014318.5%8.8%
7637105270614UAUUACAG
Tet2CR00chr4: 105272323-+UGAUAGACUCAG1022418.0%0.9%
7709105272343AGAAAGGG
Tet2CR00chr4: 105271450-+AUUUGCCUCUGA1019617.9%7.2%
7695105271470UAGAGCAU
Tet2CR00chr4: 105270330-+AUGAGAAUCAUG1013916.9%5.1%
7685105270350GAAAUCCU
Tet2CR00chr4: 105270630-+GGUCUUGUAAUU1014916.3%7.5%
7710105270649GGAGGCAG
Tet2CR00chr4: 105271921-+UUAGGUUUGACA1020816.2%16.6%
7636105271941GAGUACAA
Tet2CR00chr4: 105270194-+AUGUUGUCUGCA1013415.8%5.2%
7676105270214GGUUUCAC
Tet2CR00chr4: 105270809-−AUCCAUGUUGAU1027415.4%7.9%
7687105270829AAUUCAUU
Tet2CR00chr4: 105272562-−CUCUAGUGAGAG1048915.2%3.9%
7629105272582UGCAUACC
Tet2CR00chr4: 105271855-−GGUACUCUGAAA1030314.9%3.0%
7640105271875AGGGUAAG
Tet2CR00chr4: 105271184-+CUGUGAGGCACA1018414.6%7.3%
7627105271204UUAGCCGU
Tet2CR00chr4: 105270595-+GCCUGACUACAU1014413.6%2.3%
7630105270615AUUACAGU
Tet2CR00chr4: 105270309-−UGCUUGUCAACA1025813.5%4.9%
7650105270329CAAUUGAC
Tet2CR00chr4: 105272102-+GUGUUCAGAAGU1021313.4%4.1%
7699105272122AUGAGAUG
Tet2CR00chr4: 105271378-+AUAUAACCAUGU1019213.4%9.9%
7702105271398UUCAUUCC
Tet2CR00chr4: 105270433-−UUAACUGAUUAC1026413.1%2.1%
7678105270453AAUCUACC
Tet2CR00chr4: 105269733-+AUGGCAGCACAU1010213.0%No SD
7701105269753UGGUAAGU
Tet2CR00chr4: 105272557-−GUGAGAGUGCAU1048812.4%3.6%
7638105272577ACCUGGUA
Tet2CR00chr4: 105270620-+AAAUGGAUCGGU1014711.1%1.8%
7659105270640CUUGUAAU
Tet2CR00chr4: 105271498-+CACUAGAUAAGA1020010.7%12.0%
7705105271518ACUGAAUA
Tet2CR00chr4: 105270702-+CUAUACCAACAA1015610.6%5.2%
7641105270722AGGGUUCA
Tet2CR00chr4: 105272319-+UUCCUGAUAGAC1022210.5%1.5%
7679105272339UCAGAGAA
Tet2CR00chr4: 105271862-−AUAAGUGGGUAC103069.9%8.3%
7686105271882UCUGAAAA
Tet2CR00chr4: 105272515-+UUCUUUGGGACC102379.7%8.5%
7647105272535UGUAGUUG
Tet2CR00chr4: 105270272-+CUAGCACUCUCA101379.5%3.8%
7635105270292UGAUAGGU
Tet2CR00chr4: 105270804-+AACCUAAUGAAU101609.4%3.4%
7698105270824UAUCAACA
Tet2CR00chr4: 105270125-−GAGAUGCUGCUG105089.4%8.5%
7700105270145AUAUGGUC
Tet2CR00chr4: 105272558-−AGUGAGAGUGCA104948.7%3.8%
7661105272578UACCUGGU
Tet2CR00chr4: 105270599-−ACCCACUGUAAU102708.5%13.3%
7649105270619AUGUAGUC
Tet2CR00chr4: 105271512-+UGAAUAGGGUUA102018.4%9.1%
7674105271532AAUAUGUA
Tet2CR00chr4: 105271338-+CAGAAGUAGUAA101897.9%4.4%
7690105271358AUGAUAAC
Tet2CR00chr4: 105270244-+UGUUGCAAAGUG101356.9%10.4%
7670105270264ACCUGCUU
Tet2CR00chr4: 105272232-+GCAAGAGAGUGC102176.8%1.3%
7662105272252UUCAUUUU
Tet2CR00chr4: 105270368-−AACUGGCAAUGC102606.6%3.5%
7643105270388AUAGUCAC
Tet2CR00chr4: 105272324-−ACCCUUUCUCUG103186.1%2.4%
7681105272344AGUCUAUC
Tet2CR00chr4: 105270710-−UUAUACCCUGAA102716.1%4.4%
7657105270730CCCUUUGU
Tet2CR00chr4: 105272462-−AGUAUUCAGAUU103225.5%15.5%
7683105272482UGUGUUGG
Tet2CR00chr4: 105270131-+AUCAGCAGCAUC101305.4%2.4%
7672105270151UCAUGUUG
Tet2CR00chr4: 105272465-−CUCAGUAUUCAG103235.4%5.3%
7639105272485AUUUGUGU
Tet2CR00chr4: 105270412-+AAAAUUCAGUGC101415.4%3.7%
7642105270432CAGUUACC
Tet2CR00chr4: 105270161-+CACUGGAAUUUA101325.0%4.3%
7651105270181GUAGCAUU
Tet2CR00chr4: 105272057-+AACAGAGAGAGU102125.0%8.5%
7654105272077UAGGUGUC
Tet2CR00chr4: 105270464-−UAAGGUGAAUGG102654.9%9.1%
7694105270484CUUGUAUU
Tet2CR00chr4: 105270829-+GUAGGUGUAGUU101624.7%2.4%
7692105270849GAAGAAGA
Tet2CR00chr4: 105270385-−UCCUGGAAGUUA102614.7%1.9%
7653105270405ACUGUAAC
Tet2CR00chr4: 105271773-−UACUACAAUUAC102974.6%0.8%
7628105271793ACUAGCUU
Tet2CR00chr4: 105271863-−UAUAAGUGGGUA103074.5%1.3%
7689105271883CUCUGAAA
Tet2CR00chr4: 105271295-+AGCACCUGCUCA101884.3%3.3%
7707105271315UUAUUAGG
Tet2CR00chr4: 105271449-+AAUUUGCCUCUG101954.3%5.2%
7669105271469AUAGAGCA
Tet2CR00chr4: 105270381-+GCCAGUUACAGU101403.8%2.3%
7658105270401UAACUUCC
Tet2CR00chr4: 105271056-+UUAGGGACUGCA101773.8%1.4%
7696105271076GGCCACAU
Tet2CR00chr4: 105271172-−CCUCACAGCUUG105093.7%1.5%
7712105271192UGUUUGUA
Tet2CR00chr4: 105272231-+AGCAAGAGAGUG102163.6%1.5%
7664105272251CUUCAUUU
Tet2CR00chr4: 105272233-+CAAGAGAGUGCU102183.5%3.1%
7688105272253UCAUUUUG
Tet2CR00chr4: 105271256-−AUUUUAGAUGUU102833.5%3.7%
7704105271276GGGGUGGU
Tet2CR00chr4: 105270701-+UCUAUACCAACA101553.3%1.9%
7631105270721AAGGGUUC
Tet2CR00chr4: 105270130-−AACAUGAGAUGC105223.0%0.9%
7652105270150UGCUGAUA
Tet2CR00chr4: 105271458-−CAGAACCCAUGC102922.9%1.4%
7666105271478UCUAUCAG
Tet2CR00chr4: 105271292-+CUCAGCACCUGC101872.5%4.5%
7708105271312UCAUUAUU
Tet2CR00chr4: 105270245-−AAAGCAGGUCAC102562.5%5.9%
7660105270265UUUGCAAC
Tet2CR00chr4: 105272528-−GACAUUACAGCC103242.0%1.1%
7693105272548UCAACUAC
Tet2CR00chr4: 105272403-+UAACAGGUAGGA102311.9%1.3%
7682105272423UGGUUUUA
Tet2CR00chr4: 105271081-+UUCUGUCACAUU101811.9%1.0%
7668105271101GUUUGGUG
Tet2CR00chr4: 105270260-−AGUGCUAGUUAU102571.8%1.3%
7656105270280GCCAAAGC
Tet2CR00chr4: 105270722-+GGGUAUAAUUUU101571.7%1.8%
7663105270742GCAUGUAA
Tet2CR00chr4: 105271190-+GGCACAUUAGCC101851.6%0.9%
7625105271210GUAGGUUC
Tet2CR00chr4: 105272309-−CUAUCAGGAACA103171.6%1.3%
7644105272329GUUAGCUG
Tet2CR00chr4: 105270635-+GUAAUUGGAGGC101511.3%1.5%
7711105270655AGUGGUGA
Tet2CR00chr4: 105272395-+UUCAUUAAUAAC102301.2%1.4%
7673105272415AGGUAGGA
Tet2CR00chr4: 105270185-+UAGAGUAAUAUG101330.8%0.5%
7645105270205UUGUCUGC
Tet2CR00chr4: 105269740-+CACAUUGGUAAG10104N/AN/A
7646105269760UUGGGCUG
ControlCR00chrl: 55039271-−19.6%2.5%
1126155039291
ControlCR00chr6: 43770821-−8.4%6.9%
2318743770841
ControlCR00chr11: 116827093-−18.8%3.5%
35017116827113
ControlCR00chr2: 176122949-−35.8%8.5%
45025176122969
“SD” = standard deviation;
“No SD” = no standard deviation due to only data from one replicate only;
“N/A” = data not available due to technical error
TABLE 20
primerEditing %
Guide IDSiteCoordinateStrandset(average)SD (%)
CR007633ONTchr4:105271863-105271883+set132.87.3
CR007633ONTchr4:105271863-105271883+set232.27.2
CR007633OT 01chrX:8560771-8560791+set10.10.1
CR007633OT 01chrX:8560771-8560791+set20.10.1
CR007633OT 02chr6:109987282-109987302−set10.10.0
CR007633OT 02chr6:109987282-109987302−set20.10.0
CR007637ONTchr4:105270594-105270614+set124.47.7
CR007637ONTchr4:105270594-105270614+set226.78.4
CR007637OT 01chrX:28732099-28732119+set10.00.1
CR007637OT 01chrX:28732099-28732119+set20.00.0
CR007648ONTchr4:105271924-105271944+set124.39.1
CR007648ONTchr4:105271924-105271944+set2N/AN/A
CR007648OT 01chr1:62607266-62607286−set10.10.0
CR007648OT 01chr1:62607266-62607286−set20.20.0
CR007648OT 02chr12:6968835-6968855−set10.10.0
CR007648OT 02chr12:6968835-6968855−set20.10.0
CR007648OT 03chr17:34641080-34641100+set10.10.1
CR007648OT 03chr17:34641080-34641100+set20.10.1
CR007648OT 04chr8:142442835-142442855+set10.10.0
CR007648OT 04chr8:142442835-142442855+set20.40.3
CR007648OT 05chr1:44389438-44389458+set10.10.0
CR007648OT 05chr1:44389438-44389458+set20.10.1
CR007648OT 06chr16:57756563-57756583+set10.00.1
CR007648OT 06chr16:57756563-57756583+set20.00.0
CR007648OT 07chr20:37957777-37957797+set10.10.1
CR007648OT 07chr20:37957777-37957797+set20.00.1
CR007648OT 08chr5:94847524-94847544+set10.10.0
CR007648OT 08chr5: 94847524-94847544+set20.00.1
CR007648OT 09chr1:149886640-149886660+set10.10.1
CR007648OT 09chr1:149886640-149886660+set20.20.0
CR007648OT 10chr12:79666166-79666186+set10.10.0
CR007648OT 10chr12:79666166-79666186+set20.10.1
CR007648OT 11chr3:157114059-157114079+set10.00.0
CR007648OT 11chr3:157114059-157114079+set20.00.0
CR007648OT 12chr10:43309580-43309600+set10.00.1
CR007648OT 12chr10:43309580-43309600+set20.00.1
CR007648OT 13chr10:81383942-81383962−set10.00.0
CR007648OT 13chr10:81383942-81383962−set2N/AN/A
CR007648OT 14chr6:146406425-146406445+set10.10.1
CR007648OT 14chr6:146406425-146406445+set20.10.1
CR007648OT 15chrX:129530239-129530259+set10.10.1
CR007648OT 15chrX:129530239-129530259+set20.00.1
CR007655ONTchr4:105270144-105270164+set126.525.0
CR007655ONTchr4:105270144-105270164+set226.525.0
CR007655OT 01chr2:7990552-7990572−set10.10.1
CR007655OT 01chr2:7990552-7990572−set20.10.1
CR007655OT 02chr6:129507282-129507302+set10.00.1
CR007655OT 02chr6:129507282-129507302+set20.00.1
CR007655OT 03chr8:63331060-63331080−set12.02.1
CR007655OT 03chr8:63331060-63331080−set22.12.1
CR007655OT 04chr19:34034589-34034609+set14.03.9
CR007655OT 04chr19:34034589-34034609+set24.44.2
CR007655OT 05chr2:19636770-19636790+set10.00.1
CR007655OT 05chr2: 19636770-19636790+set20.00.0
CR007655OT 06chr21:41298867-41298887+set10.10.2
CR007655OT 06chr21:41298867-41298887+set20.10.1
CR007655OT 07chr1:239287261-239287281−set1N/AN/A
CR007655OT 07chr1:239287261-239287281−set20.10.1
CR007655OT 08chr16:750824-750844−set10.10.1
CR007655OT 08chr16:750824-750844−set20.10.1
CR007665ONTchr4:105271340-105271360+set144.911.6
CR007665ONTchr4:105271340-105271360+set246.111.4
CR007667ONTchr4:105270426-105270446−set120.52.3
CR007667ONTchr4:105270426-105270446−set220.31.2
CR007667OT 01chr9:129294818-129294838−set10.10.1
CR007667OT 01chr9:129294818-129294838−set20.10.0
CR007671ONTchr4:105270350-105270370−set124.82.0
CR007671ONTchr4:105270350-105270370−set228.22.9
CR007671OT 01chr2:224983888-224983908−set10.10.1
CR007671OT 01chr2:224983888-224983908−set20.10.0
CR007671OT 02chr1:34852545-34852565+set1N/AN/A
CR007671OT 02chr1:34852545-34852565+set2N/AN/A
CR007671OT 03chr17:81589930-81589950+set15.40.5
CR007671OT 03chr17:81589930-81589950+set23.21.5
CR007675ONTchr4:105270268-105270288+set133.84.4
CR007675ONTchr4:105270268-105270288+set233.02.8
CR007675OT 01chrX:7078173-7078193−set11.60.2
CR007675OT 01chrX:7078173-7078193−set21.60.1
CR007675OT 02chr13:33934878-33934898+set10.00.1
CR007675OT 02chr13:33934878-33934898+set20.00.0
CR007676ONTchr4:105270194-105270214+set129.25.4
CR007676ONTchr4:105270194-105270214+set230.85.0
CR007676OT 01chr1:47907842-47907862+set10.10.1
CR007676OT 01chr1:47907842-47907862+set20.10.1
CR007676OT 02chr12:93080467-93080487+set10.10.1
CR007676OT 02chr12:93080467-93080487+set20.10.0
CR007676OT 03chrX:39677001-39677021+set10.00.1
CR007676OT 03chrX:39677001-39677021+set20.10.0
CR007677ONTchr4:105271203-105271223−set125.13.5
CR007677ONTchr4:105271203-105271223−set226.32.9
CR007677OT 01chr22:43125757-43125777+set10.10.1
CR007677OT 01chr22:43125757-43125777+set20.10.1
CR007677OT 02chr1:175060841-175060861−set10.10.1
CR007677OT 02chr1:175060841-175060861−set2N/AN/A
CR007677OT 03chr11:63558842-63558862−set10.10.0
CR007677OT 03chr11:63558842-63558862−set20.00.1
CR007684ONTchr4:105272182-105272202−set120.58.8
CR007684ONTchr4:105272182-105272202−set221.16.4
CR007687ONTchr4:105270809-105270829−set140.212.9
CR007687ONTchr4:105270809-105270829−set241.512.6
CR007691ONTchr4:105272465-105272485+set137.80.9
CR007691ONTchr4:105272465-105272485+set238.01.6
CR007691OT 01chr5:167581554-167581574−set10.00.1
CR007691OT 01chr5:167581554-167581574−set20.10.1
CR007703ONTchr4:105271526-105271546+set143.810.1
CR007703ONTchr4:105271526-105271546+set243.510.8
CR007703OT 01chr6:152567788-152567808+set1N/AN/A
CR007703OT 01chr6:152567788-152567808+set20.10.1
CR007703OT 02chrX:147775642-147775662−set10.10.0
CR007703OT 02chrX:147775642-147775662−set20.30.1
CR007703OT 03chr1:73224987-73225007+set10.20.1
CR007703OT 03chr1:73224987-73225007+set20.30.0
CR007703OT 04chrX:86735755-86735775+set10.10.1
CR007703OT 04chrX:86735755-86735775+set20.00.1
CR007703OT 05chr1:185142055-185142075+set10.10.0
CR007703OT 05chr1:185142055-185142075+set20.10.1
CR007703OT 06chr5:24716285-24716305+set10.10.1
CR007703OT 06chr5:24716285-24716305+set20.00.1
CR007709ONTchr4:105272323-105272343+set116.61.9
CR007709ONTchr4:105272323-105272343+set217.51.5
CR007709OT 01chr2:129192151-129192171−set10.10.1
CR007709OT 01chr2:129192151-129192171−set20.10.0
CR007709OT 02chr2:227643116-227643136−set10.60.1
CR007709OT 02chr2:227643116-227643136−set20.40.1
CR007709OT 03chr5:138393430-138393450−set11.80.2
CR007709OT 03chr5:138393430-138393450−set22.30.7
CR007709OT 04chr1:112957752-112957772+set10.10.1
CR007709OT 04chr1:112957752-112957772+set20.10.0
CR007709OT 05chr12:68577045-68577065−set10.10.1
CR007709OT 05chr12:68577045-68577065−set20.10.1
CR007709OT 06chr3:81269842-81269862+set10.00.1
CR007709OT 06chr3:81269842-81269862+set20.10.1
CR007709OT 07chr4:99925790-99925810+set10.00.1
CR007709OT 07chr4:99925790-99925810+set20.0N/A
CR007709OT 08chr4:12791779-12791799+set10.10.1
CR007709OT 08chr4:12791779-12791799+set20.00.1
CR007709OT 09chr6:31568852-31568872−set10.10.0
CR007709OT 09chr6:31568852-31568872−set20.20.1
CR007709OT 10chr7:54279191-54279211+set1N/AN/A
CR007709OT 10chr7:54279191-54279211+set20.20.1
CR007709OT 11chr7:19117788-19117808−set11.21.3
CR007709OT 11chr7:19117788-19117808−set21.00.4
CR007709OT 12chr8:116368538-116368558−set10.10.0
CR007709OT 12chr8:116368538-116368558−set20.00.1
CR007709OT 13chr8:96115257-96115277−set10.20.1
CR007709OT 13chr8:96115257-96115277−set2N/AN/A
CR007709OT 14chrX:139885150-139885170−set10.10.0
CR007709OT 14chrX:139885150-139885170−set20.10.0
CR007709OT 15chrX:14227411-14227431+set10.10.0
CR007709OT 15chrX:14227411-14227431+set20.10.1
CR007709OT 16chr2:54814529-54814549−set10.10.1
CR007709OT 16chr2:54814529-54814549−set2N/AN/A
CR007709OT 17chr9:101349182-101349202+set10.10.1
CR007709OT 17chr9:101349182-101349202+set2N/AN/A
CR007709OT 18chr10:93489165-93489185−set10.00.1
CR007709OT 18chr10:93489165-93489185−set2N/AN/A
CR007709OT 19chr21:20954203-20954223−set12.40.1
CR007709OT 19chr21:20954203-20954223−set22.20.3
CR007709OT 20chr4:5568958-5568978−set10.00.0
CR007709OT 20chr4:5568958-5568978−set20.00.0
“ONT” = on-target site; “OT” = off-target site; “N/A” = no data due to technical error; “SD” = standard deviation
TABLE 21 — Counts of in silico off-target loci identified for the TET2 gRNAs CR007626 (g1), CR007710 (g45), CR007633, CR007665, CR007677, CR007703, CR007671, CR007675, CR007684, CR007691, g59, CR007632 (g10), CR007648 (g20), CR007709 (g34), g21, g22, g23, g55, CR007627 (g2), g4, g17, g25, g42, g54, g58, g60, TI-7 (6900), and TI-8 (7600) with 0, 1, 2, 3 and 4 nucleotide mismatches and 5 nucleotide mismatches in RefSeq exons are shown. Number of in silico off-targets with N mismatches 5 in Ref Seq
gRNA name01234exonsTotal sites
CR007626 (g1)0001374684
CR007633000712036163
CR007710 (g45)00116165104286
CR0076650011422369307
CR0076770001517779271
CR0077030001628587388
CR0076710001012849187
CR0076750016632696
CR00768400115143102261
CR0076910001918882289
g5900119196128344
CR007632 (g10)00068564155
CR007648 (g20)000913268209
CR007709 (g34)00116294118429
g210011219098301
g2200089560163
g230001514172228
g5500029313111453
CR007627 (g2)00024852102
g40001253864
g1700077858143
g25000814190239
g4200099467170
g5400528344221598
g5800529659111804
g6000029231138398
TI-7 (6900)01911512554291809
TI-8 (7600)02453546254859
TABLE 22 — Top five editing repair pattern variants generated by editing T- cells with dual gRNA moleculess comprising the targeting domains of CR007626 (g1), CR007710 (g45), CR007633, CR007665, CR007677, CR007703, CR007671, CR007675, CR007684, CR007691, g59, CR007632 (g10), CR007648 (g20), CR007709 (g34), g21, g22, g23, g55, CR007627 (g2), g4, g17, g25, g42, g54, g58, and g60 are shown. Variant size, variant type (Ins = insertion, Del = deletion), reference allele, variant allele, variant start and end position relative to chromosome 4 reference genome build GRCh38, and representative allele frequencies are shown. Variant
gRNASizeSEQ IDVariantstart andAllele
name(bp)TypeReference alleleNO:alleleend positionfrequency
CR76261InsTTT105270640-10.73%
(gl)105270641
−1DelATA105270639-9.48%
105270640
−15DelCGGTCTTGTAATT10523C105270629-4.04%
GGA105270644
−17DelATGGATCGGTCTT10524A105270623-4.01%
GTAAT105270640
−6DelTTGTAATT105270634-3.82%
105270640
CR0077−9DelGAGGCAGTGG10525G105270643-8.60%
10 (g45)105270652
−11DelGCAGTGGTGAGG10526G105270646-4.82%
105270657
−6DelGCAGTGGG105270646-4.75%
105270652
−4DelGGCAGG105270645-4.15%
105270649
−1DelGGG105270645-3.51%
105270646
CR007633−28DelAGTACCCACTTAT10527A105271870-17.79%
AT105271898
GGTCATATTTCAG
A
1InsTTT105271880-16.86%
105271881
−1DelTTT105271879-3.88%
105271880
−2DelCTTC105271878-3.33%
105271880
−2DelTATT105271880-3.17%
105271882
CR007665−1DelAAA105271356-10.91%
105271357
1InsAAA105271357-6.84%
105271358
−22DelTAAATGATAACTG10528T105271348-6.51%
GGGCTATAGT105271370
−2DelTAAT105271355-5.71%
105271357
−7DelATGATAACA105271351-5.56%
105271358
CR007677−1DelAGA105271205-12.15%
105271206
−16DelCGTAGGTTCTGGT10529C105271202-9.79%
TTCC105271218
1InsGGG105271206-5.29%
105271207
−2DelGGTG105271206-4.08%
105271208
−4DelCGTAGC105271202-3.11%
105271206
CR0077031InsAAA105271543-22.22%
105271544
−7DelGTAACAAGG105271541-6.11%
105271548
−1DelTAT105271542-5.55%
105271543
−2DelAACA105271543-4.56%
105271545
−13DelGGGAAAAGTAAC10530G105271534-3.76%
AA105271547
CR007671−2DelGTGG105270353-30.10%
105270355
1InsGGT105270353-14.16%
105270354
−2DelTGGT105270351-5.08%
105270353
−13DelAAATCCTTGGTGT10531A105270344-4.91%
T105270357
−3DelGTGTG105270353-3.42%
105270356
CR0076751InsTTT105270285-50.24%
105270286
−19DelCTCTCATGATAGG10532C105270279-10.90%
TTGGCAC105270298
−28DelTTTGGCATAACTA10533T105270263-2.74%
G105270291
CACTCTCATGATA
GG
−14DelCTAGCACTCTCAT10534C105270273-1.95%
GA105270287
−1DelCAC105270283-1.12%
105270284
CR007684−1DelTTT105272184-21.58%
105272185
−2DelGTTG105272183-12.80%
105272185
1InsTTT105272185-8.54%
105272186
−16DelCCTGTTTTTGAAG10535C105272180-4.55%
AGGC105272196
−3DelTTTTT105272185-3.54%
105272188
CR0076911InsTTT105272482-46.22%
105272483
−1DelACA105272480-14.29%
105272481
2InsTTTT105272482-4.38%
105272484
−1DelCTC105272481-2.64%
105272482
−7DelTGAATACTT105272475-1.55%
105272482
g591InsTTT105271390-18.08%
105271391
−1DelGTG105271389-15.12%
105271390
−7DelTGTTTCATT105271388-7.29%
105271395
−12DelATGTTTCATTCCA10536A105271387-4.36%
105271399
−2DelTTTT105271390-1.50%
105271392
CR0076321InsAAA105272453-4.74%
(g10)105272454
−1DelCAC105272452-4.54%
105272453
−10DelGATCAACTAGG10537G105272449-1.97%
105272459
−9DelTCTGGATCAA10538T105272445-1.21%
105272454
−2DelAACA105272453-1.00%
105272455
CR007648−1DelAAA105271940-11.98%
(g20)105271941
−15DelGTACAAAGGAGG10539G105271936-2.76%
AGAG105271951
−10DelAGAGTACAAAG10540A105271933-2.47%
105271943
−2DelCAAC105271939-2.07%
105271941
1InsAAA105271941-2.01%
105271942
CR007709−1DelAAA105272339-6.79%
(g34)105272340
1InsAAA105272340-4.22%
105272341
−2DelAAAA105272338-2.50%
105272340
−6DelAGAAAGGA105272336-1.85%
105272342
−6DelAGAGAAAA105272334-1.22%
105272340
g211InsTTT105272074-2.42%
105272075
−7DelTGTCAGGTT105272074-0.92%
105272081
−7DelAGTTAGGTA105272067-0.64%
105272074
−2DelGGTG105272072-0.40%
105272074
−11DelAGGTGTCAGGTA10541A105272071-0.16%
105272082
g22−2DelGCTG105272312-3.01%
105272314
−1DelGCG105272312-1.65%
105272313
−3DelACAGA105272309-1.11%
105272312
−19DelGAACAAGGGTCA10542G105272295-0.89%
CCACAGCT105272314
−10DelCACCACAGCTA10543C105272305-0.80%
105272315
g231InsTTA105272327-6.43%
105272328
−4DelATAGAA105272326-4.90%
105272330
−8DelTGATAGACTT105272324-1.49%
105272332
−2DelTAGT105272327-1.17%
105272329
−10DelATAGACTCAGA10544A105272326-0.80%
105272336
g55−1DelAGA105272340-7.20%
105272341
−2DelAAGA105272339-4.11%
105272341
−3DelAAAGA105272338-2.00%
105272341
−7DelAGAGAAAGA105272334-1.63%
105272341
−2DelGGGG105272341-1.41%
105272343
CR007627−6DelGCCGTAGG105271200-6.43%
(g2)105271206
−1DelGCG105271200-4.18%
105271201
−15DelGAGGCACATTAG10545G105271189-3.69%
CCGT105271204
−2DelAGCA105271199-2.02%
105271201
−7DelACATTAGCA105271194-1.54%
105271201
g4−6DelGTTCTGGG105271207-0.73%
105271213
−2DelAGGA105271205-0.37%
105271207
−1DelGGG105271206-0.27%
105271207
−10DelTAGGTTCTGGT10546T105271204-0.14%
105271214
−16DelCGTAGGTTCTGGT10547C105271202-0.11%
TTCC105271218
g17−1DelTTT105271311-9.67%
105271312
1InsTTT105271312-6.24%
105271313
−15DelTGCTCATTATTAG10548T105271302-4.65%
GAG105271317
−20DelTCATTATTAGGAG10549T105271305-3.10%
GCTATGCT105271325
−2DelATTA105271310-2.89%
105271312
g25−3DelCATTC105271306-4.39%
105271309
−1DelTTT105271308-1.50%
105271309
1InsTTT105271309-1.05%
105271310
−15DelTCATTATTAGGAG10550T105271305-0.65%
GCT105271320
−4DelTTATTT105271308-0.45%
105271312
g421InsGGA105271461-13.54%
105271462
−13ComplexGAAGAATTTGCCT10551AAGAAT105271446-2.47%
CTGATAGATT105271466
−12DelCCTCTGATAGAGC10552C105271456-2.44%
105271468
−4DelGATAGG105271461-2.39%
105271465
−17DelGATAGAGCATGG10553G105271461-1.45%
GTTCTG105271478
g54−3DelGTGGG105270649-0.99%
105270652
1InsGGT105270652-0.91%
105270653
−7DelGTGAGGGGG105270652-0.89%
105270659
−11DelGGAGGCAGTGGT10554G105270642-0.85%
105270653
−1DelGGG105270651-0.74%
105270652
g581InsCCA105271175-10.79%
105271176
−4DelCAAACC105271175-4.01%
105271179
−1DelCAC105271175-1.91%
105271176
−6DelCAAACACC105271175-1.42%
105271181
−8DelATACAAACAA105271172-1.14%
105271180
g60−3DelAGAAA105271232-0.73%
105271235
−7DelAGAACAAAA105271235-0.11%
105271242
−8DelAGAAGAACAA105271232-0.10%
105271240
-1DelAGA105271235-0.09%
105271236
1InsAAA105271235-0.07%
105271236
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IPC · International Patent Classification
Section A — Human necessities
  • A61K35/17
Section C — Chemistry; metallurgy
  • C12N9/22
  • C07K14/705
  • C12N15/113
  • C12N15/86

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