IL302315A - Safe harbor loci - Google Patents

Description

WO 2022/093846 Allllllllllllllllllllllllllllllllll Published: — ״with international search report (Art. 21(3))— before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h))— ״with sequence listing part of description (Rule 5.2(a)) WO 2022/093846 PCT/US2021/056689 SAFE HARBOR LOCI CROSS REFERENCE TO RELATED APPLICATIONS [0001]This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63/179,143, filed on April 23, 2021, U.S. Provisional Patent Application No. 63/141,926, filed on January 26, 2021, and U.S. Provisional Patent Application No. 63/105,834, filed on October 26, 2020, the entire contents of which are incorporated by reference herein for all purposes.

SEQUENCE LISTING [0002]The instant application contains a Sequence Listing which will be submitted via EFS- Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on October 15, 2021, is named ANB-203WO_SequenceListing and is 623,177 bytes in size.

BACKGROUND [0003]Cancer continues to present a significant clinical burden despite the substantial research efforts and scientific advances in cancer therapies. Blood and bone marrow cancers are frequently diagnosed cancer types, including multiple myelomas, leukemia, and lymphomas. Current treatment options for these cancers are not effective for all patients and/or can have substantial adverse side effects. Other types of cancer also remain challenging to treat using existing therapeutic options. Cancer immunotherapies are a promising solution because they can be highly specific, allowing for increased therapeutic effectiveness and the mitigation of side effects. [0004]Genetically engineered immune cell therapy is a growing field with promising applications for the treatment of diseases including, but not limited to, cancer. Through the alteration of coding and/or non-coding genomic regions, researchers are identifying transgenes and insertion sites within cells that facilitate, for example, enhanced cell function, arrest cell growth, induced cell death, and tumor size/volume reduction. The identification of safe harbor sites (SHS) has improved outcomes of genome-engineering therapies. Well known SHS include the AAVS1 adeno-associated virus insertion site on chromosome 19, the human homolog of the murine Rosa26 locus, and the CCR5 chemokine receptor gene—the absence of which confers HIV resistance. (See, for example, Pellenz et al., 2018, the relevant disclosures of which are herein incorporated by reference). However, there is still a need for improved guidelines for gene editing therapies and additional SHS to address challenges such WO 2022/093846 PCT/US2021/056689 as poor knock-in (KI) efficiency, insertional oncogenesis, unstable and/or anomalous expression of transgenes and/or adjacent genes, etc..

SUMMARY [0005]The present disclosure is directed, inter alia, to safe harbor loci that exhibit high knock-in efficiency and stable expression of their transgenes. These safe harbor loci can be used to alter T cells for immunotherapy. These safe harbor loci are useful for the treatment of various diseases, including cancer. [0006]In one aspect, the present disclosure provides an engineered cell, comprising at least one sequence encoding a transgene, wherein the at least one sequence is inserted within a safe harbor locus, the safe harbor locus is at any one or more of the sgRNA target loci provided in Table 4; and wherein expression of the at least one sequence encoding the transgene is operatively linked to an endogenous promoter. In another aspect, the present disclosure provides an engineered cell, comprising at least one sequence encoding a transgene, wherein the at least one sequence is inserted within a safe harbor locus, the safe harbor locus is at any one or more of the sgRNA target loci provided in Table 4; and wherein expression of the at least one sequence encoding the transgene is operatively linked to an exogenous promoter. [0007]In some embodiments, the target locus is selected from: chrl0:33130000-33140000, chr!0:72290000-72300000, chrl 1:128340000-128350000, chrl 1:65425000-654270(NEAT1), chrl5:92830000-92840000, chrl6:11220000-11230000, chr2:87460000- 87470000, chr3:186510000-186520000, chr3:59450000-59460000, chr8:127980000- 128000000, and chr9:7970000-7980000. In some embodiments, the target locus is selected from: chrl0:72290000-72300000, chrl 1:128340000-128350000, chrl5:92830000-92840000, and chr!6:11220000-11230000. In some embodiments, the target locus is chrl 1:128340000- 128350000. In some embodiments, the target locus is chrl5:92830000-92840000. In some embodiments, the target locus is a gene selected from: APRT, B2M, CAPNS1, CBLB, CD2, CD3E, CD3G, CDS, EDF1, FIL, PTEN, PTPN2, PTPN6, PTPRC, PTPRCAP, RPS23, RTRAF, SERF2, SLC38A1, SMAD2, SOCS1, SRP14, SRSF9, SUB1, TET2, TIGIT, TRAC, and TRIM28. [0008]In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS88, GS89, GS90, GS91, GS92, GS93, GS94, GS95, GS96, GS97, GS98, GS99, GS100, GS101, GS102, GS103, GS104, GS105, GS106, GS107, GS108, GS109, GS110, GS111, GS112, GS113, GS114, GS115, GS116, GS117, GS118, GS119, GS120. In some embodiments, the safe harbor locus is selected from any one 2 WO 2022/093846 PCT/US2021/056689 of the integration sites in Table 4 designated: GS91, GS92, GS93, GS94, GS95, GS96, GS100, GS101, GS102, GS103, GS104, and GS105. In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS103, GS104, and GS105. In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS94, GS95, and GS96. In some embodiments, the safe harbor locus is the GS94 integration site in Table 4. In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS100, GS101, and GS102. In some embodiments, the safe harbor locus is the GS102 integration site in Table 4. In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS91, GS92, and GS93. [0009]In some embodiments, the exogenous promoter is an EFla promoter. In some embodiments, the engineered cell is a stem cell, a human cell, a primary cell, an hematopoietic cell, an adaptive immune cell, an innate immune cell, a T cell or a T cell progenitor. In some embodiments, the transgene encodes a recombinant protein, optionally a therapeutic agent. In some embodiments, the transgene encodes a chimeric antigen receptor (CAR). [0010]In another aspect, the present disclosure provides a composition comprising the engineered cell as described herein and a pharmaceutical excipient. [0011]In another aspect, the present disclosure provides a guide ribonucleic acids (gRNA) for editing a cell at a safe harbor locus, wherein gRNA comprises any one of the sgRNA sequences in Table 4. [0012]In some embodiments, the gRNA comprises any one of SEQ ID NOS: 1-120. In some embodiments, the gRNA comprises any one of SEQ ID NOS: 91-96 and 100-105. In some embodiments, the gRNA comprises SEQ ID NO:94 or SEQ ID NO: 102. In some embodiments, the gRNA comprises SEQ ID NO:94. In some embodiments, the gRNA comprises SEQ ID NO: 102. In some embodiments, the cell is a stem cell, a human cell, a primary cell, an hematopoietic cell, an adaptive immune cell, an innate immune cell, a T cell or a T cell progenitor. [0013]In another aspect, the present disclosure provides a method of editing a cell having chromosomal DNA, comprising inserting at least one sequence encoding a transgene within a safe harbor locus in the chromosomal DNA of the cell, wherein the safe harbor locus is any one or more of the sgRNA target loci provided in Table 4.

WO 2022/093846 PCT/US2021/056689 id="p-14" id="p-14" id="p-14" id="p-14" id="p-14" id="p-14" id="p-14" id="p-14"

[0014]In some embodiments, the target locus is selected from: chrlO:33130000-33140000, chr!0:72290000-72300000, chrl 1:128340000-128350000, chrl 1:65425000-654270(NEAT1), chrl5:92830000-92840000, chrl6:11220000-11230000, chr2:87460000- 87470000, chr3:186510000-186520000, chr3:59450000-59460000, chr8:127980000- 128000000, and chr9:7970000-7980000. In some embodiments, the target locus is selected from: chrl0:72290000-72300000, chrl 1:128340000-128350000, chrl5:92830000-92840000, and chr!6:11220000-11230000. In some embodiments, the target locus is chrl 1:128340000- 128350000. In some embodiments, the target locus is chrl5:92830000-92840000. In some embodiments, the target locus is a gene selected from: APRT, B2M, CAPNS1, CBLB, CD2, CD3E, CD3G, CDS, EDF1, FIL, PTEN, PTPN2, PTPN6, PTPRC, PTPRCAP, RPS23, RTRAF, SERF2, SLC38A1, SMAD2, SOCS1, SRP14, SRSF9, SUB1, TET2, TIGIT, TRAC, and TRIM28. [0015]In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS88, GS89, GS90, GS91, GS92, GS93, GS94, GS95, GS96, GS97, GS98, GS99, GS100, GS101, GS102, GS103, GS104, GS105, GS106, GS107, GS108, GS109, GS110, GS111, GS112, GS113, GS114, GS115, GS116, GS117, GS118, GS119, GS120. In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS91, GS92, GS93, GS94, GS95, GS96, GS100, GS101, GS102, GS103, GS104, and GS105. In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS103, GS104, and GS105. In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS94, GS95, and GS96. In some embodiments, the safe harbor locus is the GS94 integration site in Table 4. In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS100, GS101, and GS102. In some embodiments, the safe harbor locus is the GS102 integration site in Table 4. In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS91, GS92, and GS93. [0016]In some embodiments, the transgene encodes a recombinant protein, optionally a therapeutic agent. In some embodiments, the transgene encodes a chimeric antigen receptor (CAR). In some embodiments, the at least one sequence comprises an exogenous promoter and the exogenous promoter is operably linked to the transgene. In some embodiments, the exogenous promoter is an EFla promoter. In some embodiments, the cell is a stem cell, a human cell, a primary cell, an hematopoietic cell, an adaptive immune cell, an innate immune 4 WO 2022/093846 PCT/US2021/056689 cell, a T cell or T cell progenitor. In some embodiments, the at least one sequence is inserted using a homology-directed repair. In some embodiments, the at least one sequence is inserted using a homology independent targeted insertion. In some embodiments, the at least one sequence is inserted using one or more guide ribonucleic acids (gRNAs) and one or more Cas9 endonucleases. [0017]In some embodiments, the one or more gRNAs comprises any one of SEQ ID NOS: 1-120. In some embodiments, the one or more gRNAs comprises any one of SEQ ID NOS: 91-96 and 100-105. In some embodiments, the gRNA comprises SEQ ID NO:94 or SEQ ID NO: 102. In some embodiments, the gRNA comprises SEQ ID NO:94. In some embodiments, the gRNA comprises SEQ ID NO: 102. [0018]In another aspect, the present disclosure provides a method of editing a T cell, comprising contacting a T cell with one or more guide ribonucleic acids (gRNAs), at least one sequence encoding a transgene, and one or more Cas9 endonucleases, wherein the one or more gRNAs and Cas9 endonucleases facilitate the insertion of the at least one sequence into chromosomal DNA within a safe harbor locus, wherein the safe harbor locus is selected from any one or more of the sgRNA target loci in Table 4. [0019]In some embodiments, the one or more gRNAs comprises a sequence selected from any one of the sgRNA sequences in Table 4. In some embodiments, the one or more gRNAs comprises any one of SEQ ID NOS: 1-120. In some embodiments, the one or more gRNAs comprises any one of SEQ ID NOS: 91-96 and 100-105. In some embodiments, the gRNA comprises SEQ ID NO:94 or SEQ ID NO: 102. In some embodiments, the gRNA comprises SEQ ID NO:94. In some embodiments, the gRNA comprises SEQ ID NO: 102. [0020]In some embodiments, the target locus is selected from: chrl0:33130000-33140000, chrl0:72290000-72300000, chrl 1:128340000-128350000, chrl 1:65425000-654270(NEAT1), chrl5:92830000-92840000, chrl6:11220000-11230000, chr2:87460000- 87470000, chr3:186510000-186520000, chr3:59450000-59460000, chr8:127980000- 128000000, and chr9:7970000-7980000. In some embodiments, the target locus is selected from: chrl0:72290000-72300000, chrl 1:128340000-128350000, chrl5:92830000-92840000, and chr!6:11220000-11230000. In some embodiments, the target locus is chrl 1:128340000- 128350000. In some embodiments, the target locus is chrl5:92830000-92840000. In some embodiments, the target locus is a gene selected from: APRT, B2M, CAPNS1, CBLB, CD2, CD3E, CD3G, CDS, EDF1, FIL, PTEN, PTPN2, PTPN6, PTPRC, PTPRCAP, RPS23, WO 2022/093846 PCT/US2021/056689 RTRAF, SERF2, SLC38A1, SMAD2, S0CS1, SRP14, SRSF9, SUB1, TET2, TIGIT, TRAC, and TRIM28. [0021]In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS88, GS89, GS90, GS91, GS92, GS93, GS94, GS95, GS96, GS97, GS98, GS99, GS100, GS101, GS102, GS103, GS104, GS105, GS106, GS107, GS108, GS109, GS110, GS111, GS112, GS113, GS114, GS115, GS116, GS117, GS118, GS119, GS120. In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS91, GS92, GS93, GS94, GS95, GS96, GS100, GS101, GS102, GS103, GS104, and GS105. In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS103, GS104, and GS105. In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS94, GS95, and GS96. In some embodiments, the safe harbor locus is the GS94 integration site in Table 4. In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS100, GS101, and GS102. In some embodiments, the safe harbor locus is the GS102 integration site in Table 4. In some embodiments, the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS91, GS92, and GS93 [0022]In another aspect, the present disclosure provides an ex vivo method of obtaining an engineered cell or population thereof, comprising (a) obtaining a cell; and (b) genetically modifying the cell by inserting at least one sequence encoding a transgene within a safe harbor locus, wherein the safe harbor locus is selected from any one of the sgRNA target loci in Table 4. [0023]In some embodiments, obtaining the cell comprises: (i) collecting a tissue sample from a subject, (ii) isolating the cells from the tissue samples, and (iii) culturing the cells in vitro. In some embodiments, the tissue sample is a blood sample. In some embodiments, the cell is a stem cell, a human cell, a primary cell, an hematopoietic cell, an adaptive immune cell, an innate immune cell, a T cell or T cell precursor (T cell progenitor). In some embodiments, the at least one sequence is inserted using a homology-directed repair. In some embodiments, the at least one sequence is inserted using a homology independent targeted insertion. [0024]In some embodiments, the genetically modifying in step (b) comprises contacting the cell with one or more guide ribonucleic acids (gRNAs), the at least one sequence, and one or more Cas9 endonucleases, wherein the one or more gRNAs and Cas9 endonucleases facilitate 6 WO 2022/093846 PCT/US2021/056689 the insertion of the at least one sequence into chromosomal DNA within the safe harbor locus. In some embodiments, the one or more gRNAs comprises a sequence selected from any one of the sgRNA sequences in Table 4. [0025]In some embodiments, the transgene encodes a recombinant protein, optionally a therapeutic agent. In some embodiments, the transgene encodes a chimeric antigen receptor (CAR). In some embodiments, the at least one sequence comprises an exogenous promoter and the exogenous promoter is operably linked to the transgene. In some embodiments, the exogenous promoter is an EFla promoter. [0026]In yet another aspect, the present disclosure provides a method of treating a subject having or at risk of having a disease, comprising administering to the subject an effective amount of an engineered cell as described herein, a population thereof, or a composition as described herein. In some embodiments, the cell, the population thereof, or the composition is administered to the subject by infusion. [0027]In yet another aspect, the present disclosure provides a method of treating a subject having or at risk of having a disease, comprising (a) conducting any one of the methods described supra; and (b) administering to the subject an effective amount of a composition comprising the cell or a population thereof. In some embodiments, the composition is administered to the subject by infusion. In some embodiments, the disease is cancer. In some embodiments, the disease is blood cancer. [0028]In another aspect, the present disclosure provides a method of identifying a safe harbor locus, comprising: (a) identifying genes or non-coding regions in a chromosome that are above a threshold level for expression across developmental cell states and/or a threshold level for accessibility of chromatin; (b) generating a linear model that correlates the gene or non-coding region from step (a) with knock-in (KI) efficiency and estimates the KI efficiency of any gene or coding region on the chromosome; and (c) selecting the safe harbor locus based on threshold parameters; wherein the safe harbor locus is selected for insertion of at least one sequence encoding a transgene within a cell. [0029]In some embodiments, the threshold parameters include one or more of: stable expression of a transgene, knockout of the gene confers benefit to the function of the cell, no known function within the cell, stable transgene expression in vitro with or without CD3/CD28 stimulation, negligible off-target cleavage as detected by iGuide-Seq or CRISPR- Seq, less off-target cleavage relative to other loci as detected by iGuide-Seq or CRISPR-Seq, negligible transgene-independent cytotoxicity, negligible transgene-independent cytokine 7 WO 2022/093846 PCT/US2021/056689 expression, negligible transgene-independent chimeric antigen receptor expression, negligible deregulation or silencing of nearby genes, and positioned outside of a cancer-related gene. In some embodiments, the stable expression of a transgene at the safe harbor locus is less than or equal to 2-fold expression change over the course of at least 1, 2, 3, 4, 5, 6, or 7 days, and wherein expression change is measured by mean fluorescence intensity of a reporter gene encoded by the at least one sequence. In some embodiments, the accessibility of chromatin is measured using an assay for transposase-accessible chromatin using sequencing (ATAC-seq). In some embodiments, the level of expression across developmental cell states is measured using RNA sequencing (RNA-seq). [0030]In some embodiments, the cell is a stem cell, a human cell, a primary cell, an hematopoietic cell, an adaptive immune cell, an innate immune cell, a T cell or T cell progenitor. In some embodiments, the linear model has a coefficient of determination (Rvalue) of at least 30%. [0031]In yet another aspect, the present disclosure provides an engineered cell, composition, gRNA or method as described herein, wherein insertion within the safe harbor locus increase cell cytotoxicity of diseased cells. [0032]In yet another aspect, the present disclosure provides an engineered cell, composition, gRNA or method as described herein, wherein knock-in efficiency at the safe harbor locus is increased relative to other locations along the chromosome.

BRIEF DESCRIPTION OF THE DRAWINGS [0033]These and other features, aspects, and advantages of the present invention will become better understood with regard to the following description, and accompanying drawings, where: [0034] FIG. 1includes a schematic depicting the methodology used to identify safe harbor loci in the present disclosure, in some embodiments. [0035] FIGS. 2A-2Cinclude schematic depicting 3 top safe harbor loci known in the art: AAVS1 (FIG. 2A),CCR5 (FIG. 2B),and Rosa26 (FIG. 2C).The figures were retrieved from Sadelain, M., et al. (2012). Safe harbours for the integration of new DNA in the human genome. Nature reviews Cancer, 12(1), 51-58, the relevant disclosures of which are herein incorporated by reference in their entirety. [0036] FIG. 3includes a schematic outlining the data provided in Roth, T. L., et al. 2019. Rapid discovery of synthetic DNA sequences to rewrite endogenous T cell circuits. bioRxiv, WO 2022/093846 PCT/US2021/056689 604561, the relevant disclosures of which are herein incorporated by reference in their entirety. [0037] FIGS. 4A-4Binclude heatmaps with samples clustered based on activation status and cell type, generated with processed RNA-seq data. FIG. 4Aincludes a heatmap of samples generated with processed RNA-seq data. FIG. 4Bincludes a heatmap sample generated with processed RNA-seq data, showing the clustering of ~20k genes. [0038] FIGS. 5A-5Binclude plots generated using processed RNA-seq data. FIG. 5A includes a plot showing direct correlation between transcript expression data from Roth, T.L., et al. 2019 and transcript expression data generated by the inventors of the present disclosure. FIG.5Bincludes a heatmap showing clusters of the top 10% expressed genes. [0039] FIG. 6includes a heatmap of samples generated with processed ATAC-seq data. [0040] FIGS. 7A-7Bincludes plots depicting the signal enrichment at transcription start sites (TSS) (FIG.7A) and peak size distribution (FIG. 7B),generated with processed ATAC-seq data for coding regions. [0041] FIG. 8includes a plot depicting the open chromatin regions around the TRAC locus. [0042] FIG. 9includes a plot depicting KI (knock-in) efficiency for coding regions/genes with GFP as a reporter. [0043] FIG. 10includes a plot depicting KI efficiency for coding regions/genes with tNGFR as a reporter. [0044] FIG. 11includes plots showing scaled KI efficiency for 90 genes vs d2 (day-2) RNA- seq data, d4 (day-4) RNA-seq data and ATAC-seq data, utilized for the predictive linear model. [0045] FIG. 12includes a plot showing chromatin accessibility for a top candidate non- coding region, measured using ATAQ sequencing. [0046] FIG. 13Aincludes plots showing the cell counts for GFP controls used for the evaluation of candidate KI loci. FIG. 13Bincludes pmax (GFP_high) readings for GFP controls used for the evaluation of candidate KI loci. [0047] FIG. 14Aincludes plots showing the maximum episomal GFP expression (GFP_high) readings for non-targeting controls. FIG. 14Bincludes the cell count for non- targeting controls from donors 1, 2, and 3. [0048] FIG. 15includes the cell count and maximum GFP expression (GFP_high) readings for WT controls.

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[0049] FIG. 16includes plots showing the cell count and maximum GFP expression (GFP_high) readings when using sgRNA5, which targets a B2M safe harbor locus, and the construct expression was driven by an endogenous promoter. [0050] FIG. 17includes plots showing the cell count and maximum GFP expression (GFP_high) readings when using sgRNA5, which targets a B2M safe harbor locus, and the construct expression was driven by an EFla promoter. [0051] FIG. 18includes plots showing the cell count and maximum GFP expression (GFP_high) readings when using sgRNA79 to target a TRAC safe harbor locus, and the construct expression was driven by an endogenous promoter. [0052] FIG. 19includes plots showing the cell count and maximum GFP expression (GFP_high) readings when using sgRNA79, which targets a TRAC safe harbor locus, and the construct expression was driven by an exogenous promoter. [0053] FIG. 20includes plots showing TCR (T cell receptor) vs. GFP among all donors and time points when using sgRNA79, and the construct is driven by an endogenous promoter. [0054] FIG. 21includes plots showing TCR vs. GFP among all donors and time points when using sgRNA79 and the construct is driven by an exogenous promoter. [0055] FIG. 22includes plots showing the cell count and maximum GFP expression (GFP_high) readings when using sgRNA83, which targets a TRAC safe harbor locus, and the construct expression was driven by an endogenous promoter. [0056] FIG. 23includes plots showing the cell count and maximum GFP expression (GFP_high) readings when using sgRNA83, which targets a TRAC safe harbor locus, and the construct expression was driven by an exogenous promoter. [0057] FIG. 24includes plots showing TCR vs. GFP among all donors and time points when using sgRNA83 and the construct is driven by an endogenous promoter. [0058] FIG. 25includes plots showing TCR vs. GFP among all donors and time points when using sgRNA83 and the construct is driven by an exogenous promoter. [0059] FIG. 26includes plots illustrating potential sources of variation (e.g., edge effects and electroporation errors) observed between replicates and donors. [0060] FIG. 27includes plots illustrating potential sources of variation observed between replicates and donors, e.g., relating to inherent differences between donors. [0061] FIG. 28includes plots illustrating potential sources of variation observed between replicates and donors, e.g., relating to gating errors.

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[0062] FIG. 29includes plots showing the GFP mean fluorescence intensity (GFP MFI) and KI efficiency for top KI loci evaluated with endogenous promoters. [0063] FIG. 30includes plots showing the GFP mean fluorescence intensity (GFP MFI) and KI efficiency for top KI loci evaluated with the EFla promoter. [0064] FIGS. 31A-31Cinclude plots showing all the significant KI loci (top KI loci) as evaluated with endogenous and EFla promoters. FIG. 31Aincludes a plot showing that the expression from the EFla promoter was approximately 10 times higher than expression from an endogenous promoter. FIG. 31Bshows the top KI loci ranked by GFP MFI at week 3. FIG. 31Cshows the top integration loci ranked by GFP MFI (at weeks 3 and 4; donors 1-3). [0065] FIG. 32Aincludes a plot showing some target loci and their measured transgene expression levels. FIG. 32Bincludes plots showing the transgene (Prime Receptor (PrimeR)) and TCR expression for the control and insertion at GS94, GS102 and TRAC loci. [0066] FIG. 33Aincludes a plot showing the PrimeR levels measured for the indicated integration sites. FIG. 33Bincludes a schematic showing the GS94 integration site on Chromosome 11. [0067] FIG. 34Aincludes plots showing CAR induction and primeR expression of engineered T cells after 48 hours of coculturing with K562-CD19 cells. FIG. 34Bincludes plots showing the cytotoxity and cytokine secretion levels for engineered T cells 48 hours of coculturing with K562-CD19/MSLN cells. [0068] FIG. 35Aincludes a schematic showing the experimental overview for evaluating the effect of integration site on cytotoxicity. FIG. 35Bincludes plots showing the measured cytotoxicity for engineerred T cells cocultured for 48 hours with the K562 CD19+/MSLN+ or K562 CD19-/MSLN+ cells. [0069] FIG. 36Aincludes a schematic showing the experimental overview for evaluating the effect of integration site on cytokine secretion. FIG. 36Bincludes plots showing the measured cytokine levels for engineerred T cells cocultured for 48 hours with K5CD19+/MSLN+ cells. [0070] FIG. 37includes a schematic showing the in vitro experiment conducted to determin the effect of integration site on primeR-independent CAR expression. "Flow" refers to flow cytometry and "restim" refers to repetitive CD3/CD28 stimualation of the engineered T cells. "EP" refers to electroporation. [0071] FIGS. 38A and 38Binclude plots showing the stability of PrimeR expression over time when using the indicated integration sites. "Flow" refers to flow cytometry and "restim" 11 WO 2022/093846 PCT/US2021/056689 refers to repetitive CD3/CD28 stimualation of the engineered T cells. "EP" refers to electroporation. In FIG. 38B,the PrimeR expression is normalized to the expression from using the TRAC integration site. [0072] FIG. 39Aincludes a schematic showing the iGuide-Seq assay technique. FIG. 39B includes a plot showing the on-target efficiency, using iGuide Seq assay, for the indicated integration sites. FIG. 39Cincludes schematics from the iGuide-Seq analysis showing that GS94 had no reproducible putatitve off-targets across two donors. [0073] FIG. 40includes a schematic showing the iGuide-Seq workflow and data. [0074] FIG. 41includes a plot showing rhAmp-seq analysis of putative off-target sites identified by iGUIDE-seq and Elevation prediction. [0075] FIG. 42includes plots showing RNA-seq analysis of cells with GS94, GS102 and TRAC knock-in of CD19/MSLN circuits. Scatterplot of gene expression in cells with integration at the GS94 locus (y-axis) vs cells with integration at either the TRAC or the GS102 locus (x-axis) in two donors. The yellow dots correspond to ETS1 and FLU. In blue are the genes that were found to be differentially expressed using edgeR (fold-change > 0, FDR-corrected p-value < 0.01, average counts-per-million across compared conditions at least 2). [0076] FIG. 43includes plots showing the absence of cytokine-independent growth in cells with CD19/MSLN circuit KI at GS94. [0077] FIG. 44shows a diagram of a 8.3 kb cassette that was inserted into the GS94 safe harbor locus. [0078] FIG. 45shows the expression of a 8.3 kb transgene circuit comprising a priming receptor and CAR in K562 cells. [0079] FIG. 46shows that non-viral editing generated less differentiated T cells.

DETAILED DESCRIPTION [0080]The present disclosure provides safe harbor loci and methods for identifying safe harbor loci that exhibit high integration efficiency (e.g., high knock-in (KI) efficiency), high and constant levels of transgene expression, and such benefits independent of T cell activation/differentiation state. In some embodiments, the safe harbor loci also exhibit minimal to no disruption to T cell function and/or capacity for product manufacturing. In some embodiments, these loci are useful for effective and safe integration and expression of transgenes in T cells (e.g. in CAR T therapies). In some embodiments, the methods described WO 2022/093846 PCT/US2021/056689 herein can be used for the identification of safe harbor loci for insertion of transgenes in other types of cells. [0081] FIG. 1illustrates the overall approach that the inventors of the present disclosure used to identify safe harbor loci. In some embodiments, the present disclosure provides a method comprising the identification of genes within a genome and non-coding regions with sustained expression in a treatment cell (e.g. T cell) and using a predictive model of KI efficiency as a function of T cell chromatic state and computational analysis to predict candidate integration sites. The method further comprises evaluating the candidate integration sites for actual KI efficiency, sustained levels of transgene expression of a transgene, and minimal disruption to the treatment cell phenotype (e.g., T cell function and/or capacity for treatment product expansion and manufacturing). In some embodiments, the safe harbor loci allow for integration of a transgene driven by an endogenous promoter. In some embodiments, the safe harbor loci allow for integration of a transgene driven by an exogenous promoter (e.g. EFla promoter). [0082]To facilitate an understanding of the present disclosure, a number of terms and phrases are defined below. Unless otherwise defined herein, scientific and technical terms used in this application shall have the meanings that are commonly understood by those of ordinary skill in the art. Generally, nomenclature used in connection with, and techniques of pharmacology, cell and tissue culture, molecular biology, cell and cancer biology, neurobiology, neurochemistry, virology, immunology, microbiology, genetics and protein and nucleic acid chemistry, described herein, are those well-known and commonly used in the art. In case of conflict, the present specification, including definitions, will control. [0083]Unless otherwise defined, all terms of art, notations and other scientific terminology used herein are intended to have the meanings commonly understood by those of skill in the art. In some cases, terms with commonly understood meanings are defined herein for clarity and/or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a difference over what is generally understood in the art. The techniques and procedures described or referenced herein are generally well understood and commonly employed using conventional methodologies by those skilled in the art, such as, for example, the widely utilized molecular cloning methodologies described in Sambrook et al., Molecular Cloning: A Laboratory Manual 4th ed. (2012) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. As appropriate, procedures involving the use of WO 2022/093846 PCT/US2021/056689 commercially available kits and reagents are generally carried out in accordance with manufacturer-defined protocols and conditions unless otherwise noted. [0084]As used herein, the singular forms "a," "an," and "the" include the plural referents unless the context clearly indicates otherwise. The terms "include," "such as," and the like are intended to convey inclusion without limitation, unless otherwise specifically indicated. [0085]As used herein, the term "comprising" also specifically includes embodiments "consisting of’ and "consisting essentially of’ the recited elements, unless specifically indicated otherwise. [0086]The term "about" indicates and encompasses an indicated value and a range above and below that value. In certain embodiments, the term "about" indicates the designated value ± 10%, ± 5%, or ± 1%. In certain embodiments, where applicable, the term "about" indicates the designated value(s) ± one standard deviation of that value(s). [0087]As used herein, the term "gene" refers to the basic unit of heredity, consisting of a segment of DNA arranged along a chromosome, which codes for a specific protein or segment of protein. A gene typically includes a promoter, a 5' untranslated region, one or more coding sequences (exons), optionally introns, a 3' untranslated region. The gene may further comprise a terminator, enhancers and/or silencers. [0088]As used herein, the term "locus" refers to a specific, fixed physical location on a chromosome where a gene or genetic marker is located. [0089]As used herein, the term "target locus" refers to a locus on a chromosome within which a safe harbor locus can be used for the insertion of a sequence. A target locus can consist of multiple potential safe harbor loci (integration sites). Examples of target loci are provided in Table 4, as sgRNA target loci. The notation used for the sgRNA target loci in Table 4 refers to the genomic region of the target locus, defined by the chromosome of the target locus and the coordinate range for that target locus. For example, chrl0:33130000- 33140000 refers to a target locus on ChrlO (chromosome 10) starting from coordinate 33130000 and ending with coordinate 33140000. [0090]The term "safe harbor locus" refers to a locus at which genes or genetic elements can be incorporated without disruption to expression or regulation of adjacent genes. These safe harbor loci are also referred to as safe harbor sites (SHS). As used herein, a safe harbor locus refers to an "integration site" or "knock-in site" at which a sequence encoding a transgene, as defined herein, can be inserted. In some embodiments the insertion occurs with replacement of a sequence that is located at the integration site. In some embodiments, the insertion occurs 14 WO 2022/093846 PCT/US2021/056689 without replacement of a sequence at the integration site. Examples of integration sites contemplated are provided in Table 4. [0091]As used herein, the term "insert" refers to a nucleotide sequence that is integrated (inserted) at a safe harbor site. The insert can be used to refer to the genes or genetic elements that are incorporated at the safe harbor site using, for example, homology-directed repair (HDR) CRISPR/Cas9 genome-editing or other methods for inserting nucleotide sequences into a genomic region known to those of ordinary skill in the art. [0092]The "CRISPR/Cas" system refers to a widespread class of bacterial systems for defense against foreign nucleic acid. CRISPR/Cas systems are found in a wide range of eubacterial and archaeal organisms. CRISPR/Cas systems include type I, II, and III sub- types. Wild-type type II CRISPR/Cas systems utilize an RNA-mediated nuclease,Cas9 in complex with guide and activating RNA to recognize and cleave foreign nucleic acid. Guide RNAs having the activity of both a guide RNA and an activating RNA are also known in the art. In some cases, such dual activity guide RNAs are referred to as a small guide RNA (sgRNA). [0093]Cas9 homologs are found in a wide variety of eubacteria, including, but not limited to bacteria of the following taxonomic groups: Actinobacteria, Aquificae, Bacteroidetes- Chlorobi, Chlamydiae-Verrucomicrobia, Chlroflexi, Cyanobacteria, Firmicutes, Proteobacteria, Spirochaetes, and Thermotogae. An exemplary Cas9 protein is the Streptococcus pyogenes Cas9 protein. Additional Cas9 proteins and homologs thereof are described in, e.g., Chylinksi, et al., RNA Biol. 2013 May 1; 10(5): 726-737 ; Nat. Rev. Microbiol. 2011 lune; 9(6): 467-477; Hou, etal., Proc Natl Acad Sci USA. 2013 Sep 24;110(39):15644-9; Sampson et al., Nature. 2013 May 9;497(7448):254-7; and linek, et al., Science. 2012 Aug 17;337(6096):816-21. The Cas9 nuclease domain can be optimized for efficient activity or enhanced stability in the host cell. [0094]As used herein, the term "Cas9" refers to an RNA-mediated nuclease (e.g., of bacterial or archeal orgin, or derived therefrom). Exemplary RNA-mediated nuclases include the foregoing Cas9 proteins and homologs thereof, and include but are not limited to, CPF(See, e.g., Zetsche etal., Cell, Volume 163, Issue 3, p759-771, 22 October 2015). Similarly, as used herein, the term "Cas9 ribonucleoprotein" complex and the like refers to a complex between the Cas9 protein, and a crRNA (e.g., guide RNA or small guide RNA), the Casprotein and a trans-activating crRNA (tracrRNA), the Cas9 protein and a small guide RNA, WO 2022/093846 PCT/US2021/056689 or a combination thereof (e.g, a complex containing the Cas9 protein, a tracrRNA, and a crRNA guide RNA). [0095]As used herein, the terms "T lymphocyte" and "T cell" are used interchangeably and refer to cells that have completed maturation in the thymus, and identify certain foreign antigens in the body. The terms also refer to the major leukocyte types that have various roles in the immune system, including activation and deactivation of other immune cells. The T cell can be any T cell such as a cultured T cell, e.g., a primary T cell, or a T cell derived from a cultured T cell line, e.g., a Jurkat, SupTl, etc., or a T cell obtained from a mammal. The T cell can be a CD3 + cell. The T cell can be any type of T cell, CD4 + / CDS + double positive T cells, CD4 + helper T cells (e.g. Thl and Th2 cells), CDS + T cells (e.g. cytotoxic T cells), peripheral Including but not limited to blood mononuclear cells (PBMC), peripheral blood leukocytes (PBL), tumor infiltrating lymphocytes (TIL), memory T cells, naive T cells, regulatory T cells, y5 T cells, etc. It can be any T cell at any stage of development. Additional types of helper T cells include Th3 (Treg) cells, Thl? cells, Th9 cells, or Tfh cells. Additional types of memory T cells include cells such as central memory T cells (Tcm cells), effector memory T cells (Tem cells and TEMRA cells). A T cell can also refer to a genetically modified T cell, such as a T cell that has been modified to express a T cell receptor (TCR) or a chimeric antigen receptor (CAR). T cells can also be differentiated from stem cells or progenitor cells (e.g., precursor cells). [0096]،،CD4 + T cells" refers to a subset of T cells that express CD4 on their surface and are associated with a cellular immune response. CD4 + T cells are characterized by a post- stimulation secretion profile that can include secretion of cytokines such as IFN-y, TNF-a, IL-2, IL-4 and IL-10. "CD4" is a 55 kD glycoprotein originally defined as a differentiation antigen on T lymphocytes, but was also found on other cells including monocytes / macrophages. The CD4 antigen is a member of the immunoglobulin superfamily and has been implicated as an associative recognition element in MHC (major histocompatibility complex) class II restricted immune responses. On T lymphocytes, the CD4 antigen defines a helper / inducer subset. [0097]،،CDS + T cells" refers to a subset of T cells that express CDS on their surface, are MHC class I restricted, and function as cytotoxic T cells. The "CDS" molecule is a differentiation antigen present on thymocytes, as well as on cytotoxic and suppressor T lymphocytes. The CDS antigen is a member of the immunoglobulin superfamily and is an WO 2022/093846 PCT/US2021/056689 associative recognition element in major histocompatibility complex class I restriction interactions. [0098]As used herein, the term "ex vivo" generally includes experiments or measurements made in or on living tissue, preferably in an artificial environment outside the organism, preferably with minimal differences from natural conditions. [0099]As used herein, the term "construct" refers to a complex of molecules, including macromolecules or polynucleotides. [00100]As used herein, the term "integration" refers to the process of stably inserting one or more nucleotides of a construct into the cell genome, i.e., covalently linking to a nucleic acid sequence in the chromosomal DNA of the cell. It may also refer to nucleotide deletions at a site of integration. Where there is a deletion at the insertion site, "integration" may further include substitution of the endogenous sequence or nucleotide deleted with one or more inserted nucleotides. [00101]As used herein, the term "exogenous" refers to a molecule or activity that has been introduced into a host cell and is not native to that cell. The molecule can be introduced, for example, by introduction of the encoding nucleic acid into host genetic material, such as by integration into a host chromosome, or as non-chromosomal genetic material, such as a plasmid. Thus, the term, when used in connection with expression of an encoding nucleic acid, refers to the introduction of the encoding nucleic acid into a cell in an expressible form. The term "endogenous" refers to a molecule or activity that is present in a host cell under natural, unedited conditions. Similarly, the term, when used in connection with expression of the encoding nucleic acid, refers to expression of the encoding nucleic acid that is contained within the cell and not introduced exogenously. [00102]As used herein, a "polynucleotide donor construct" refers to a nucleotide sequence (e.g. DNA sequence) that is genetically inserted into a polynucleotide and is exogenous to that polynucleotide. The polynucleotide donor construct is transcribed into RNA and optionally translated into a polypeptide. The polynucleotide donor construct can include prokaryotic sequences, cDNA from eukaryotic mRNA, genomic DNA sequences from eukaryotic (e.g., mammalian) DNA, and synthetic DNA sequences. For example, the polynucleotide donor construct can be a miRNA, shRNA, natural polypeptide (i.e., a naturally occurring polypeptide) or fragment thereof or a variant polypeptide (e.g. a natural polypeptide having less than 100% sequence identity with the natural polypeptide) or fragments thereof.17 WO 2022/093846 PCT/US2021/056689 id="p-103" id="p-103" id="p-103" id="p-103" id="p-103" id="p-103" id="p-103" id="p-103"

[00103]As used herein, the term "transgene" refers to a polynucleotide that has been transferred naturally, or by any of a number of genetic engineering techniques from one organism to another. It is optionally translated into a polypeptide. It is optionally translated into a recombinant protein. A "recombinant protein" is a protein encoded by a gene — recombinant DNA — that has been cloned in a system that supports expression of the gene and translation of messenger RNA (see expression system). The recombinant protein can be a therapeutic agent, e.g. a protein that treats a disease or disorder disclosed herein. As used, transgene can refer to a polynucleotide that encodes a polypeptide. A transgene can also refer to a non-encoding sequence, such as, but not limited to shRNAs, miRNAs, and miRs. [00104]The terms "protein," "polypeptide," and "peptide" are used herein interchangeably. [00105]As used herein, the term "operably linked" refers to the binding of a nucleic acid sequence to a single nucleic acid fragment such that one function is affected by the other. For example, if a promoter is capable of affecting the expression of a coding sequence or functional RNA (i.e., the coding sequence or functional RNA is under transcriptional control by the promoter), the promoter is operably linked thereto. Coding sequences can be operably linked to control sequences in both sense and antisense orientation. [00106]As used herein, the term "developmental cell states" refers to, for example, states when the cell is inactive, actively expressing, differentiating, senescent, etc. developmental cell state may also refer to a cell in a precursor state (e.g., a T cell precursor or T cell progenitor). [00107]As used, the term "encoding" refers to a sequence of nucleic acids which codes for a protein or polypeptide of interest. The nucleic acid sequence may be either a molecule of DNA or RNA. In preferred embodiments, the molecule is a DNA molecule. In other preferred embodiments, the molecule is a RNA molecule. When present as a RNA molecule, it will comprise sequences which direct the ribosomes of the host cell to start translation (e.g., a start codon, ATG) and direct the ribosomes to end translation (e.g., a stop codon). Between the start codon and stop codon is an open reading frame (ORF). Such terms are known to one of ordinary skill in the art. [00108]The term "inserting" refers to a manipulation of a nucleotide sequence to introduce a non-native sequence. This is done, for example, via the use of restriction enzymes and ligases whereby the DNA sequence of interest, usually encoding the gene of interest, can be incorporated into another nucleic acid molecule by digesting both molecules with 18 WO 2022/093846 PCT/US2021/056689 appropriate restriction enzymes in order to create compatible overlaps and then using a ligase to join the molecules together. One skilled in the art is very familiar with such manipulations and examples may be found in Sambrook et al. (Sambrook, Fritsch, & Maniatis, "Molecular Cloning: A Laboratory Manual", 2nd ed., Cold Spring Harbor Laboratory, 1989), which is hereby incorporated by reference in its entirety including any drawings, figures and tables. [00109]As used herein, the term "subject" refers to a mammalian subject. Exemplary subjects include humans, monkeys, dogs, cats, mice, rats, cows, horses, camels, goats, rabbits, pigs and sheep. In certain embodiments, the subject is a human. In some embodiments the subject has a disease or condition that can be treated with an engineered cell provided herein or population thereof. In some aspects, the disease or condition is a cancer. [00110]As used herein, the term "promoter" refers to a nucleotide sequence (e.g. DNA sequence) capable of controlling the expression of a coding sequence or functional RNA. The promoter sequence consists of proximal and more distal upstream elements, the latter elements often referred to as enhancers. A promoter can be derived from natural genes in its entirety, can be composed of different elements from different promoters found in nature, and/or may comprise synthetic DNA segments. A promoter, as contemplated herein, can be endogenous to the cell of interest or exogenous to the cell of interest. It is appreciated by those skilled in the art that different promoters can induce gene expression in different tissue or cell types, or at different developmental stages, or in response to different environmental conditions. As is known in the art, a promoter can be selected according to the strength of the promoter and/or the conditions under which the promoter is active, e.g., constitutive promoter, strong promoter, weak promoter, inducible/repressible promoter, tissue specific Or developmentally regulated promoters, cell cycle-dependent promoters, and the like. [00111]A promoter can be an inducible promoter (e.g., a heat shock promoter, tetracycline- regulated promoter, steroid-regulated promoter, metal-regulated promoter, estrogen receptor- regulated promoter, etc.). The promoter can be a constitutive promoter (e.g., CMV promoter, UBC promoter). In some embodiments, the promoter can be a spatially restricted and/or temporally restricted promoter (e.g., a tissue specific promoter, a cell type specific promoter, etc.). See for example US Application No. 15/715,068, the disclosures of which are herein incorporated by reference in their entirety. [00112]Gene editing, as contemplated herein, may involve a gene (or nucleotide sequence) knock-in or knock-out. As used herein, the term "knock-in" refers to an addition of a DNA sequence, or fragment thereof into a genome. Such DNA sequences to be knocked-in 19 WO 2022/093846 PCT/US2021/056689 may include an entire gene or genes, may include regulatory sequences associated with a gene or any portion or fragment of the foregoing. For example, a polynucleotide donor construct encoding a recombinant protein may be inserted into the genome of a cell carrying a mutant gene. In some embodiments, a knock-in strategy involves substitution of an existing sequence with the provided sequence, e.g., substitution of a mutant allele with a wild-type copy. On the other hand, the term "knock-out" refers to the elimination of a gene or the expression of a gene. For example, a gene can be knocked out by either a deletion or an addition of a nucleotide sequence that leads to a disruption of the reading frame. As another example, a gene may be knocked out by replacing a part of the gene with an irrelevant (.e.g., non-coding) sequence. [00113]As used herein, the term "non-hom 01 ogous end joining" or NHEJ refers to a cellular process in which cut or nicked ends of a DNA strand are directly ligated without the need for a homologous template nucleic acid. NHEJ can lead to the addition, the deletion, substitution, or a combination thereof, of one or more nucleotides at the repair site. [00114]As used herein, the term "homology directed repair" or HDR refers to a cellular process in which cut or nicked ends of a DNA strand are repaired by polymerization from a homologous template nucleic acid. Thus, the original sequence is replaced with the sequence of the template. The homologous template nucleic acid can be provided by homologous sequences elsewhere in the genome (sister chromatids, homologous chromosomes, or repeated regions on the same or different chromosomes). Alternatively, an exogenous template nucleic acid can be introduced to obtain a specific HDR-induced change of the sequence at the target site. In this way, specific mutations can be introduced at the cut site. [00115]The terms "vector" and "plasmid" are used interchangeably and as used herein refer to polynucleotide vehicles useful to introduce genetic material into a cell. Vectors can be linear or circular. Vectors can integrate into a target genome of a host cell or replicate independently in a host cell. Vectors can comprise, for example, an origin of replication, a multicloning site, and/or a selectable marker. An expression vector typically comprises an expression cassette. Vectors and plasmids include, but are not limited to, integrating vectors, prokaryotic plasmids, eukaryotic plasmids, plant synthetic chromosomes, episomes, viral vectors, cosmids, and artificial chromosomes. [00116]As used herein the term "expression cassette" is a polynucleotide construct, generated recombinantly or synthetically, comprising regulatory sequences operably linked to a selected polynucleotide to facilitate expression of the selected polynucleotide in a host cell.20 WO 2022/093846 PCT/US2021/056689 For example, the regulatory sequences can facilitate transcription of the selected polynucleotide in a host cell, or transcription and translation of the selected polynucleotide in a host cell. An expression cassette can, for example, be integrated in the genome of a host cell or be present in an expression vector. [00117]As used herein, the phrase "subject in need thereof’ refers to a subject that exhibits and/or is diagnosed with one or more symptoms or signs of a disease or disorder as described herein. [00118]A "chemotherapeutic agent" refers to a chemical compound useful in the treatment of cancer. Chemotherapeutic agents include "anti-hormonal agents" or "endocrine therapeutics" which act to regulate, reduce, block, or inhibit the effects of hormones that can promote the growth of cancer. [00119]The term "composition" refers to a mixture that contains, e.g., an engineered cell or protein contemplated herein. In some embodiments, the composition may contain additional components, such as adjuvants, stabilizers, excipients, and the like. The term "composition" or "pharmaceutical composition" refers to a preparation which is in such form as to permit the biological activity of an active ingredient contained therein to be effective in treating a subject, and which contains no additional components which are unacceptably toxic to the subject in the amounts provided in the pharmaceutical composition. [00120]As used herein, the term "effective amount" refers to the amount of a compound (e.g., a compositions described herein, cells described herein) sufficient to effect beneficial or desired results. An effective amount can be administered in one or more administrations, applications or dosages and is not intended to be limited to a particular formulation or administration route. As used herein, the term "treating" includes any effect, e.g., lessening, reducing, modulating, ameliorating or eliminating, that results in the improvement of the condition, disease, disorder, and the like, or ameliorating a symptom thereof. [00121]The terms "modulate" and "modulation" refer to reducing or inhibiting or, alternatively, activating or increasing, a recited variable. [00122]The terms "increase" and "activate" refer to an increase of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or greater in a recited variable. [00123]The terms "reduce" and "inhibit" refer to a decrease of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or greater in a recited variable.21 WO 2022/093846 PCT/US2021/056689 Safe Harbor Loci [00124]Gene editing therapies include, for example, viral vector integration and site specific integration. Site-specific integration is a promising alternative to random integration of viral vectors, as it mitigates the risks of insertional mutagenesis or insertional oncogenesis (Kolb et al. Trends Biotechnol. 2005 23:399-406; Porteus et al. Nat Biotechnol. 2005 23:967- 973; Paques et al. Curr Gen Ther. 2007 7:49-66). However, site specific integration continues to face challenges such as poor knock-in efficiency, risk of insertional oncogenesis, unstable and/or anomalous expression of adjacent genes or the transgene, low accessibility (e.g. within kB of adjacent genes), etc.. These challenges can be addressed, in part, through the identification and use of safe harbor loci or safe harbor sites (SHS), which are sites in which genes or genetic elements can be incorporated without disruption to expression or regulation of adjacent genes. [00125]The most widely used of the putative human safe harbor sites is the AAVS1 site on chromosome 19q, which was initially identified as a site for recurrent adenoassociated virus insertion. Other potential SHS have been identified on the basis of homology, with sites first identified in other species (e.g., the human homolog of the permissive murine Rosa26 locus) or among the growing number of human genes that appear non-essential under some circumstances. One putative SHS of this type is the CCR5 chemokine receptor gene, which, when disrupted, confers resistance to human immunodeficiency virus infection. Additional potential genomic SHS have been identified in human and other cell types on the basis of viral integration site mapping or gene-trap analyses, as was the original murine Rosa26 locus. The three top SHS, AAVS1, CCR5, and Rosa26, are in close proximity to many protein coding genes and regulatory elements. (See FIG. 2from Sadelain, M., et al.(2012). Safe harbours for the integration of new DNA in the human genome. Nature reviews Cancer, 12(1), 51-58, the relevant disclosures of which are herein incorporated by reference in their entirety). [00126]The AAVS1 (also known as the PPP1R12C locus) on human chromosome 19 is a known SHS for hosting transgenes (e.g. DNA transgenes) with expected function. It is at position 19ql3.42. It has an open chromatin structure and is transcription-competent. The canonical SHS locus for AAVS1 is chrl9: 55,625,241-55,629,351. See Pellenz et al. "New Human Chromosomal Sites with "Safe Harbor" Potential for Targeted Transgene Insertion." Human gene therapy vol. 30,7 (2019): 814-828, the relevant disclosures of which are herein WO 2022/093846 PCT/US2021/056689 incorporated by reference. An exemplary AAVS1 target gRNA and target sequence are provided below:• AAVS1-gRNA sequence:ggggccactagggacaggatGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTA GTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTT• AAVS1 target sequence: ggggccactagggacaggat [00127] CCR5,which is located on chromosome 3 at position 3p21.31, encodes the major co-receptor for HIV-1. Disruption at this site in the CCR5 gene has been beneficial in HIV/AIDS therapy and prompted the development of zinc-finger nucleases that target its third exon. The canonical SHSlocus for CCR5is chr3: 46,414,443-46,414,942. See Pellenz et al. "New Human Chromosomal Sites with "Safe Harbor" Potential for Targeted Transgene Insertion." Human gene therapy vol. 30,7 (2019): 814-828, the relevant disclosures of which are herein incorporated by reference. [00128]The mouse Rosa26 locus is particularly useful for genetic modification as it can be targeted with high efficiency and is expressed in most cell types tested. Irion et al. 20("Identification and targeting of the ROSA26 locus in human embryonic stem cells." Nature biotechnology 25.12 (2007): 1477-1482, the relevant disclosure of which are herein incorporated by reference) identified the human homolog, human ROSA26, in chromosome (position 3p25.3).The canonical SHS locus for human Rosa26 (hR0sa26) is chr3: 9,415,082- 9,414,043. See Pellenz et al. "New Human Chromosomal Sites with "Safe Harbor" Potential for Targeted Transgene Insertion." Human gene therapy vol. 30,7 (2019): 814-828, the relevant disclosures of which are herein incorporated by reference. [00129]Additional examples of safe harbor sites are provided in Pellenz et al. "New Human Chromosomal Sites with "Safe Harbor" Potential for Targeted Transgene Insertion." Human gene therapy vol. 30,7 (2019): 814-828, the relevant disclosures of which are herein incorporated by reference. [00130]The present disclosure is directed to methods for identifying safe harbor loci with benefits including, but not limited to, high knock-in efficiency and high expression of transgene. An example of applications of the presently disclosed methods is the identification of safe harbor loci for insertion of transgenes (e.g., chimeric antigen receptors (CAR)) into T- cells. In some embodiments, the safe harbor loci of the present disclsoure are useful for the insertion of a sequence encoding a transgene. In some embodiments, the safe harbor sites allow for high transgene expression (sufficient to allow for transgene functionality or 23 WO 2022/093846 PCT/US2021/056689 treatment of a disease of interest) and stable expression of the transgene over several days, weeks or months. In some embodiments, knockout of the gene at the safe harbor locus confers benefit to the function of the cell, or the gene at the safe harbor locus has no known function within the cell. In some embodiments the safe harbor locus results in stable transgene expression in vitro with or without CD3/CD28 stimulation, negligible off-target cleavage as detected by iGuide-Seq or CRISPR-Seq, less off-target cleavage relative to other loci as detected by iGuide-Seq or CRISPR-Seq, negligible transgene-independent cytotoxicity, negligible transgene-independent cytokine expression, negligible transgene- independent chimeric antigen receptor expression, negligible deregulation or silencing of nearby genes, and positioned outside of a cancer-related gene. [00131]As used, a "nearby gene" can refer to a gene that is within about 100kB, about 125kB, about 150kB, about 175kB, about 200kB, about 225kB, about 250kB, about 275kB, about 300kB, about 325kB, about 350kB, about 375kB, about 400kB, about 425kB, about 450kB, about 475kB, about 500kB, about 525kB, about 550kB away from the safe harbor locus (integration site). [00132]In some embodiments, the present disclosure contemplates inserts that comprise one or more transgenes. The transgene can encode a therapeutic protein, an antibody, a peptide, a suicide gene, an apoptosis gene or any other gene of interest. The safe harbor loci identified using the method described herein allow for transgene integration that results in , for example, enhanced therapeutic properties. These enhanced therapeutic properties, as used herein, refer to an enhanced therapeutic property of a cell when compared to a typical immune cell of the same normal cell type. For example, an NK cell having "enhanced therapeutic properties" has an enhanced, improved, and/or increased treatment outcome when compared to a typical, unmodified and/or naturally occurring NK cell. The therapeutic properties of immune cells can include, but are not limited to, cell transplantation, transport, homing, viability, self-renewal, persistence, immune response control and regulation, survival, and cytotoxicity. The therapeutic properties of immune cells are also manifested by: antigen-targeted receptor expression; HLA presentation or lack thereof; tolerance to the intratumoral microenvironment; induction of bystander immune cells and immune regulation; improved target specificity with reduction; resistance to treatments such as chemotherapy. [00133]As used herein, the term "insert size" refers to the length of the nucleotide sequence being integrated (inserted) at the safe harbor site. In some embodiments, the insert size comprises at least about 100, 200, 300, 400 or 500 basepairs. In some embodiments, the 24 WO 2022/093846 PCT/US2021/056689 insert size comprises about 500 nucleotides or basepairs. In some embodimetns, the insert size comprises up to 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 kbp (kilo basepairs) or the sizes in between. In some embodiments, the insert size is greater than 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 kbp or the sizes in between. In some embodiments, the insert size is within the range of 3-15 kbp or is any number in that range. In some embodiments, the insert size is within the range of 1.5-8.3 kbp or is any number in that range. In some embodiments, the insert size is within the range of 1.5-15 kbp or is any number in that range. In some embodiments, the insert size is within the range of 0.5-20 kbp or is any number in that range. In some embodiments, the insert size is 0.5-10, 0.6-10, 0.7-10, 0.8-10, 0.9-10, 1-10, 2-10, 3- 10, 4-10, 5-10, 6-10, 7-10, 8-10, 9-10 kbp. In some embodiments, the insert size is 0.5-11, 0.6-11, 0.7-11, 0.8-11, 0.9-11, 1-11, 2-11, 3-11, 4-11, 5-11, 6-11, 7-11, 8-11, 9-11, or 10-kbp. In some embodiments, the insert size is 0.5-12, 0.6-12, 0.7-12, 0.8-12, 0.9-12, 1-12, 2- 12, 3-12, 4-12, 5-12, 6-12, 7-12, 8-12, 9-12, 10-12, or 11-12 kbp. In some embodiments, the insert size is 0.5-13, 0.6-13, 0.7-13, 0.8-13, 0.9-13, 1-13, 2-13, 3-13, 4-13, 5-13, 6-13, 7-13, 8-13, 9-13, 10-13, 11-13, or 12-13 kbp. In some embodiments, the insert size is 0.5-14, 0.6- 14, 0.7-14, 0.8-14, 0.9-14, 1-14, 2-14, 3-14, 4-14, 5-14, 6-14, 7-14, 8-14, 9-14, 10-14, 11-14, 12-14 or 13-14 kbp. In some embodiments, the insert size is 0.5-15, 0.6-15, 0.7-15, 0.8-15, 0.9-15, 1-15, 2-15, 3-15, 4-15, 5-15, 6-15, 7-15, 8-15, 9-15, 10-15, 11-15, 12-15, 13-15, or 14-15 kbp. In some embodiments, the insert size is 0.5-16, 0.6-16, 0.7-16, 0.8-16, 0.9-16, 1- 16, 2-16, 3-16, 4-16, 5-16, 6-16, 7-16, 8-16, 9-16, 10-16, 11-16, 12-16, 13-16, 14-16 or 15-kbp. In some embodiments, the insert size is 0.5-17, 0.6-17, 0.7-17, 0.8-17, 0.9-17, 1-17, 2- 17, 3-17, 4-17, 5-17, 6-17, 7-17, 8-17, 9-17, 10-17, 11-17, 12-17, 13-17, or 14-17, 15-17 or 16-17 kbp. In some embodiments, the insert size is 0.5-18, 0.6-18, 0.7-18, 0.8-18, 0.9-18, 1- 18, 2-18, 3-18, 4-18, 5-18, 6-18, 7-18, 8-18, 9-18, 10-18, 11-18, 12-18, 13-18, 14-18, 15-18, 16-18 or 17-18 kbp. In some embodiments, the insert size is 0.5-19, 0.6-19, 0.7-19, 0.8-19, 0.9-19, 1-19, 2-19, 3-19, 4-19, 5-19, 6-19, 7-19, 8-19, 9-19, 10-19, 11-19, 12-19, 13-19, 14- 19, 15-19, 16-19, 17-19, or 18-19 kbp. In some embodiments, the insert size is 0.5-20, 0.6-20, 0.7-20, 0.8-20, 0.9-20, 1-20, 2-20, 3-20, 4-20, 5-20, 6-20, 7-20, 8-20, 9-20, 10-20, 11-20, 12- 20, 13-20, 14-20, 15-20, 16-20, 17-20, 18-20, or 19-20 kbp. [00134]The inserts of the present disclosure refer to nucleic acid molecules or polynucleotide inserted at a safe harbor site. In some embodiments, the nucleotide sequence is a DNA molecule, e.g., genomic DNA, or comprises deoxy-ribonucleotides. In some 25 WO 2022/093846 PCT/US2021/056689 embodiments, the insert comprises a smaller fragment of DNA, such as a plastid DNA, mitochondrial DNA, or DNA isolated in the form of a plasmid, a fosmid, a cosmid, a bacterial artificial chromosome (BAC), a yeast artificial chromosome (YAC), and/or any other sub-genome segment of DNA. In some embodiments, the insert is an RNA molecule or comprises ribonucleotides. The nucleotides in the insert are contemplated as naturally occuring nucleotides, non-naturally occuring, and modified nucleotides. Nucleotides may be modified chemically or biochemically, or may contain non-natural or derivatized nucleotide bases, as will be readily appreciated by those of skill in the art. Such modifications include, for example, labels, methylation, substitution of one or more of the naturally occurring nucleotides with an analog, internucleotide modifications. The polynucleotides can be in any topological conformation, including single-stranded, double-stranded, partially duplexed, triplexed, hairpinned, circular conformations, and other three-dimension conformations contemplated in the art. [00135]The inserts can have coding and/or non-coding regions. The insert can comprises a non-coding sequence (e.g., control elements, e.g., a promoter sequence). In some embodiments, the insert encodes transcription factors. In some embodiments, the insert encodes an antigen binding receptors such as single receptors, T-cell receptors (TCRs), syn- notch, CARs, mAbs, etc. In some embodiments, the inserts are RNAi molecules, including, but not limited to, miRNAs, siRNA, shRNAs, etc. In some embodiments, the the insert is a human sequence. In some embodiments, the insert is chimeric. In some embodiments, the insert is a multi-gene/multi-module therapeutic cassette. A multi-gene/multi-module therapeutic cassette referst to an insert or cassette having one or more than one receptor (e.g., synthetic receptors), other exogenous protein coding sequences, non-coding RNAs, transcriptional regulatory elements, and/or insulator sequences, etc. [00136]Various cell types are contemplated as having the safe harbor sites in the present disclosure. A cell comprising a safe harbor site and/or a cell comprising an insert at a safe harbor site as described in the present disclosure can be referred to as an engineered cell. The cells can include, but are not limited to, eukaryotic cells, prokaryotic cells, animal cells, plant cells, fungal cells and the like. Optionally, the cell is a mammalian cell, for example, a human cell. In some embodiments, that engineered cell is a stem cell, a human cell, a primary cell, an hematopoietic cell, an adaptive immune cell, an innate immune cell, a T cell or a T cell progenitor. Non-limiting examples of immune cells that are contemplated in the present disclosure include T cell, B cell, natural killer (NK) cell, NKT/iNKT cell, 26 WO 2022/093846 PCT/US2021/056689 macrophage, myeloid cell, and dendritic cells. Non-limiting examples of stem cells that are contemplated in the present disclosure include pluripotent stem cells (PSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), embryo-derived embryonic stem cells obtained by nuclear transfer (ntES; nuclear transfer ES), male germline stem cells (GS cells), embryonic germ cells (EG cells), hematopoietic stem/progenitor stem cells (HSPCs), somatic stem cells (adult stem cells), hemangioblasts, neural stem cells, mesenchymal stem cells and stem cells of other cells (including osteocyte, chondrocyte, myocyte, cardiac myocyte, neuron, tendon cell, adipocyte, pancreocyte, hepatocyte, nephrocyte and follicle cells and so on). In some embodiments, the engineered cells is a T cell, NK cells, iPSC, and HSPC. In some embodiments, the engineered cells used in the present disclosure are human cell lines grown in vitro (e.g. deliberately immortalized cell lines, cancer cell lines, etc?). [00137]The methods for integrating the inserts at the safe harbor sites can be viral or non- viral delivery techniques. [00138]In some embodiments, the nucleic acid sequence is inserted into the genome of the engineered cell by introducing a vector, for example, a viral vector, comprising the nucleic acid. Examples of viral vectors include, but are not limited to, adeno-associated viral (AAV) vectors, retroviral vectors or lentiviral vectors. In some embodiments, the lentiviral vector is an integrase-deficient lentiviral vector. [00139]In some embodiments, the nucleic acid sequence is inserted into the genome of the T cell via non-viral delivery. In non-viral delivery methods, the nucleic acid can be naked DNA, or in a non-viral plasmid or vector. Non-viral delivery techniques can be site-specific integration techniques, as described herein or known to those of ordinary skill in the art. Examples of site-specific techniques for integration into the safe harbor loci include, without limitation, homology-dependent engineering using nucleases and homology independent targeted insertion using Cas9. In some embodiments, the non-viral delivery method comprises electroporation. [00140]In some embodiments, the insert is integrated at a safe harbor site by introducing into the engineered cell, (a) a targeted nuclease that cleaves a target region in the safe harbor site to create the insertion site; and (b) the nucleic acid sequence (insert), wherein the insert is incorporated at the insertion site by, e.g., HDR. Examples of non-viral delivery techniques that can be used in the methods of the present disclosure are provided in US Application Nos. 16/568,116 and 16/622,843, the relevant disclosures of which are herein incorporated by reference in their entirety.27 WO 2022/093846 PCT/US2021/056689 id="p-141" id="p-141" id="p-141" id="p-141" id="p-141" id="p-141" id="p-141" id="p-141"

[00141]The engineered cell can retain its undifferentiated state after insertion of the transgenes. In some embodiments, the engineered cell is undifferentiated. In some embodiments, the engineered cell is undifferentiated after insert of the transgene. In some embodiments, the engineered cell is CD45RA+ and CCR7+ after insertion of the transgene. In some embodiments, the engineered cell is CD45RA+CCR7+CD27+ after insertion of the transgene.

CAR T cell Therapy [00142]Chimeric antigen receptor (CAR) T cells are T cells that have been genetically engineered to produce an artificial T-cell receptor for use in immunotherapy. Chimeric antigen receptors are receptor proteins that have been engineered to confer T cells with the ability to target a specific protein. The genetic modification of lymphocytes (e.g. T cells) by incorporation of, for example, CARs, and administration of the engineered cells to a subject is an example of "adoptive cell therapy". As used herein, the term "adoptive cell therapy" refers to cell-based immunotherapy for transfusion of autologous or allogeneic lymphocytes, referred to as T cells or B cells. In this CAR therapy approach, cells are expanded and cultured ex vivo and genetically modified, prior to transfusion. [00143]The expression of CARs allows the engineered T-cells to target and bind specific proteins, for example, tumor antigens. In CAR therapy, T-cells are harvested from a subject—they can be autologous T-cells from the subject own blood or from a donor that will not be receiving the CAR therapy. Once isolated, the T-cells are genetically modified with a CAR, expanded ex vivo, and administered to the subject (z.e. patient) by, e.g. infusion. [00144]The CARs may be introduced into the T-cells using, for example, a viral technique (e.g., retroviral integration) or site-specific technique. With site specific integration of the transgenes (e.g. CARs), the transgenes may be targeted to a safe harbor locus.Examples of site-specific techniques for integration into the safe harbor loci include, without limitation, homology-dependent engineering using nucleases and homology independent targeted insertion using Cas9. [00145]The engineered CAR T cells have applications to immune-oncology. The CAR, for example, can be selected to target a specific tumor antigen. Examples of cancers that can be effectively targeted using CAR T cells are blood cancers. In some embodiments, CAR T cell therapy can be used to treat solid tumors.

WO 2022/093846 PCT/US2021/056689 Gene editing [00146]The terms "gene editing" or "genome editing", as used herein, refer to a type of genetic manipulation in which DNA is inserted, replaced, or removed from the genome using artificially manipulated nucleases or "molecular scissors". It is a useful tool for elucidating the function and effect of sequence-specific genes or proteins or altering cell behavior (e.g. for therapeutic purposes). [00147]Currently available genome editing tools include zinc finger nucleases (ZFN) and transcription activator-like effector nucleases (T ALENs) to incorporate genes at safe harbor loci (.e.g. the adeno-associated virus integration site 1 (AAVS1) safe harbor locus). The DICE (dual integrase cassette exchange) system utilizing phiC31 integrase and Bxbl integrase is a tool for target integration. Additionally, clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) techniques can be used for targeted gene insertion. [00148]Site specific gene editing approaches can include homology dependent mechanisms or homology independent mechanisms. [00149]All methods known in the art for targeted insertion of gene sequences are contemplated in the methods described herein to insert constructs at safe harbor loci.

Crispr-Cas Gene editing [00150]One effective example of gene editing is the Crisp-Cas approach (e.g. Crispr- Cas9). This approach incorporates the use of a guide polynucleotide (e.g. guide ribonucleic acid or gRNA) and a cas endonuclease (e.g. Cas9 endonuclease). [00151]As used herein, a polypeptide referred to as a "Cas endonuclease" or having "Cas endonuclease activity" refers to a CRISPR-related (Cas) polypeptide encoded by a Cas gene, wherein a Cas polypeptide is a target DNA sequence that can be cleaved when operably linked to one or more guide polynucleotides (see, e.g., US Pat. No. 8,697,359). Also included in this definition are variants of Cas endonuclease that retain guide polynucleotide-dependent endonuclease activity. The Cas endonuclease used in the donor DNA insertion method detailed herein is an endonuclease that introduces double-strand breaks into DNA at the target site (e.g., within the target locus or at the safe harbor site). [00152]As used herein, the term "guide polynucleotide" relates to a polynucleotide sequence capable of complexing with a Cas endonuclease and allowing the Cas endonuclease to recognize and cleave a DNA target site. The guide polynucleotide can be a single molecule or a double molecule. The guide polynucleotide sequence can be an RNA sequence, a DNA sequence, or a combination thereof (RNA-DNA combination sequence). A guide 29 WO 2022/093846 PCT/US2021/056689 polynucleotide comprising only ribonucleic acid is also referred to as "guide RNA". In some embodiments, a polynucleotide donor construct is inserted at a safe harbor locus using a guide RNA (gRNA) in combination with a cas endonuclease (e.g. Cas9 endonuclease). [00153]The guide polynucleotide includes a first nucleotide sequence domain (also referred to as a variable targeting domain or VT domain) that is complementary to a nucleotide sequence in the target DNA, and a second nucleotide that interacts with a Cas endonuclease polypeptide. It can be a double molecule (also referred to as a double-stranded guide polynucleotide) comprising a sequence domain (referred to as a Cas endonuclease recognition domain or CER domain). The CER domain of this double molecule guide polynucleotide comprises two separate molecules that hybridize along the complementary region. The two separate molecules can be RNA sequences, DNA sequences and/or RNA- DNA combination sequences. [00154]Genome editing using CRISPR-Cas approaches relies on the repair of site-specific DNA double-strand breaks (DSBs) induced by the RNA-guided Cas endonuclease (e.g. Cas endonuclease). Homology-directed repair (HDR) of these DSBs enables precise editing of the genome by introducing defined genomic changes, including base substitutions, sequence insertions, and deletions. Conventional HDR-based CRISPR/Cas9 genome-editing involves transfecting cells with Cas9, gRNA and donor DNA containing homologous arms matching the genomic locus of interest. [00155]HITI (homology independent targeted insertion) uses a non-homologous end joining (NHEJ)-based homology-independent strategy and the method can be more efficient than HDR. Guide RNAs (gRNAs) target the insertion site. For HITI, donor plasmids lack homology arms and DSB repair does not occur through the HDR pathway. The donor polynucleotide construct can be engineered to include Cas9 cleavage site(s) flanking the gene or sequence to be inserted. This results in Cas9 cleavage at both the donor plasmid and the genomic target sequence. Both target and donor have blunt ends and the linearized donor DNA plasmid is used by the NHEJ pathway resulting integration into the genomic DSB site. (See, for example, Suzuki, K., et al. (2016). In vivo genome editing via CRISPR/Casmediated homology-independent targeted integration. Nature, 540(7631), 144-149, the relevant disclosures of which are herein incorporated in their entirety). [00156]Methods for conducing gene editing using CRISPR-Cas approaches are known to those of ordinary skill in the art. (See, for example, US Application Nos. US16/312,676, US 15/303,722, and US 15/628,533, the disclosures of which are herein incorporated by 30 WO 2022/093846 PCT/US2021/056689 reference in their entirety). Additionally, uses of endonucleases for inserting transgenes into safe harbor loci are described, for example, in US Application No. 13/036,343, the disclosures of which are herein incorporated by reference in their entirety. [00157]The guide RNAs and/or mRNA (or DNA) encoding an endonuclease can be chemically linked to one or more moi eties or conjugates that enhance the activity, cellular distribution, or cellular uptake of the oligonucleotide. Non-limiting examples of such moieties include lipid moieties such as a cholesterol moiety, cholic acid, a thioether, a thiocholesterol, an aliphatic chain (e.g., dodecandiol or undecyl residues), a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethylammonium 1 ,2-di-O-hexadecyl- rac-glycero-3-H- phosphonate, a polyamine or a polyethylene glycol chain, adamantane acetic acid, a palmityl moiety and an octadecylamine or hexylamino-carbonyl-t oxycholesterol moiety. See for example US Application No. 15/715,068, the disclosures of which are herein incorporated by reference in their entirety.

Therapeutic Applications [00158]For therapeutic applications, the engineered cells, populations thereof, or compositions thereof are administered to a subject, generally a mammal, generally a human, in an effective amount. [00159]The engineered cells may be administered to a subject by infusion (e.g., continuous infusion over a period of time) or other modes of administration known to those of ordinary skill in the art. [00160]The engineered cells provided herein can be administered as part of a pharmaceutical compositions. In some embodimetns, the present disclosure provides compositions comprising a guide RNA of the present disclosure. The pharmaceutical composition may comprise one or more pharmaceutical excipients. Any suitable pharmaceutical excipient may be used, and one of ordinary skill in the art is capable of selecting suitable pharmaceutical excipients. Accordingly, the pharmaceutical excipients provided below are intended to be illustrative, and not limiting. Additional pharmaceutical excipients include, for example, those described in the Handbook of Pharmaceutical Excipients, Rowe etal. (Eds.) 6th Ed. (2009), incorporated by reference in its entirety. [00161]The engineered cells provided herein not only find use in gene therapy but also in non-pharmaceutical uses such as, e.g., production of animal models and production of recombinant cell lines expressing a protein of interest.

WO 2022/093846 PCT/US2021/056689 id="p-162" id="p-162" id="p-162" id="p-162" id="p-162" id="p-162" id="p-162" id="p-162"

[00162]The engineered cells of the present disclosure can be any cell, generally a mammalian cell, generally a human cell that has been modified by integrating a transgene at a safe harbor locus described herein. In some embodiments, the engineered cells are immune cells. In some embodiments, the engineered cells are lymphocytes. In some embodiments, the engineered cells are T cells or T cell progenitors. [00163]The engineered cells, compositions and methods of the present disclosure are useful for therapeutic applications such as CAR T cell therapy and TCR T cell therapy. In some embodiments, the insertion of a sequence encoding a transgene within a safe harbor locus maintains the TCR expression relative to instances when there is no insertion and enables transgene expression while maintaining TCR function. [00164]Various diseases treated using the engineered cells, populations thereof, or compositions thereof are provided herein. Non-limiting examples of such diseases include alopecia areata, autoimmune hemolytic anemia, autoimmune hepatitis, cancer, dermatomyositis, diabetes (type 1), certain juvenile idiopathic arthritis, glomerulonephritis, Graves' disease, Guillain Valley Syndrome, idiopathic thrombocytopenic purpura, myasthenia gravis, certain myocarditis, multiple sclerosis, pemphigus/pemphigoid, pernicious anemia, polyarteritis nodosa, polymyositis, primary bile With cirrhosis, psoriasis, rheumatoid arthritis, scleroderma/systemic sclerosis, Sjogren's syndrome, systemic lupus erythematosus, certain thyroiditis, certain uveitis, vitiligo, multiple vasculitis (Wegener)); autoimmune disorders including, but not limited to, granulomatosis; hematopoietic tumors including but not limited to acute and chronic leukemia, lymphoma, multiple myeloma and myelodysplastic syndrome; tumors of the prostate, breast, lung, colon, uterus, skin, liver, bone, pancreas, ovary, testis, bladder, kidney, head, neck, stomach, cervix, rectum, larynx, or esophagus solid tumors; HIV (human immunodeficiency virus) related disorders, RSV (respiratory syncytial virus) related disorders; EBV (Epstein-Barr virus) related disorders; CMV (cytomegalovirus) related disorders; and infectious diseases including, but not limited to, adenovirus-related disorders and BK polyomavirus-related disorders. [00165]Cancers that can be treated with the engineered cells (e.g., CAR T-cells) of the present disclosure, populations thereof, or compositions thereof include blood cancers. In some embodiments, the cancer treated using the engineered cells (e.g., CAR T-cells) described herein, populations thereof, or compositions thereof is a hematologic malignancy or leukemia. In some embodiments, the engineered cells (e.g., CAR T-cells) described herein, populations thereof, or compositions thereof are used for the treatment of acute 32 WO 2022/093846 PCT/US2021/056689 lymphoblastic leukemia (ALL) or diffuse large B-cell lymphoma (DLBCL). In some embodiments, the cancer is acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplasia, myelodysplastic syndromes, acute T-lymphoblastic leukemia, or acute promyelocytic leukemia, chronic myelomonocytic leukemia, or myeloid blast crisis of chronic myeloid leukemia. Examples of cancers treatable using the engineered cells (e.g., CAR T-cells) described herein include, without limitation, breast cancer, ovarian cancer, esophageal cancer, bladder or gastric cancer, salivary duct carcinoma, salivary duct carcinomas, adenocarcinoma of the lung or aggressive forms of uterine cancer, such as uterine serous endometrial carcinoma. In some other embodiments, the cancer is brain cancer, breast cancer, cervical cancer, colon cancer, colorectal cancer, endometrial cancer, esophageal cancer, leukemia, lung cancer, liver cancer, melanoma, ovarian cancer, pancreatic cancer, rectal cancer, renal cancer, stomach cancer, testicular cancer, or uterine cancer. In yet other embodiments, the cancer is a squamous cell carcinoma, adenocarcinoma, small cell carcinoma, melanoma, neuroblastoma, sarcoma (e.g., an angiosarcoma or chondrosarcoma), larynx cancer, parotid cancer, biliary tract cancer, thyroid cancer, acral lentiginous melanoma, actinic keratoses, acute lymphocytic leukemia, acute myeloid leukemia, adenoid cystic carcinoma, adenomas, adenosarcoma, adenosquamous carcinoma, anal canal cancer, anal cancer, anorectum cancer, astrocytic tumor, bartholin gland carcinoma, basal cell carcinoma, biliary cancer, bone cancer, bone marrow cancer, bronchial cancer, bronchial gland carcinoma, carcinoid, cholangiocarcinoma, chondrosarcoma, choroid plexus papilloma/carcinoma, chronic lymphocytic leukemia, chronic myeloid leukemia, clear cell carcinoma, connective tissue cancer, cystadenoma, digestive system cancer, duodenum cancer, endocrine system cancer, endodermal sinus tumor, endometrial hyperplasia, endometrial stromal sarcoma, endometrioid adenocarcinoma, endothelial cell cancer, ependymal cancer, epithelial cell cancer, Ewing's sarcoma, eye and orbit cancer, female genital cancer, focal nodular hyperplasia, gallbladder cancer, gastric antrum cancer, gastric fundus cancer, gastrinoma, glioblastoma, glucagonoma, heart cancer, hemangioblastomas, hemangioendothelioma, hemangiomas, hepatic adenoma, hepatic adenomatosis, hepatobiliary cancer, hepatocellular carcinoma, Hodgkin's disease, ileum cancer, insulinoma, intraepithelial neoplasia, interepithelial squamous cell neoplasia, intrahepatic bile duct cancer, invasive squamous cell carcinomajejunum cancer,joint cancer, Kaposi's sarcoma, pelvic cancer, large cell carcinoma, large intestine cancer, leiomyosarcoma, lentigo maligna melanomas, lymphoma, male genital cancer, malignant melanoma, malignant mesothelial tumors, 33 WO 2022/093846 PCT/US2021/056689 medulloblastoma, medulloepithelioma, meningeal cancer, mesothelial cancer, metastatic carcinoma, mouth cancer, mucoepidermoid carcinoma, multiple myeloma, muscle cancer, nasal tract cancer, nervous system cancer, neuroepithelial adenocarcinoma nodular melanoma, non-epithelial skin cancer, non-Hodgkin's lymphoma, oat cell carcinoma, oligodendroglial cancer, oral cavity cancer, osteosarcoma, papillary serous adenocarcinoma, penile cancer, pharynx cancer, pituitary tumors, plasmacytoma, pseudosarcoma, pulmonary blastoma, rectal cancer, renal cell carcinoma, respiratory system cancer, retinoblastoma, rhabdomyosarcoma, sarcoma, serous carcinoma, sinus cancer, skin cancer, small cell carcinoma, small intestine cancer, smooth muscle cancer, soft tissue cancer, somatostatin- secreting tumor, spine cancer, squamous cell carcinoma, striated muscle cancer, submesothelial cancer, superficial spreading melanoma, T cell leukemia, tongue cancer, undifferentiated carcinoma, ureter cancer, urethra cancer, urinary bladder cancer, urinary system cancer, uterine cervix cancer, uterine corpus cancer, uveal melanoma, vaginal cancer, verrucous carcinoma, VIPoma, vulva cancer, well-differentiated carcinoma, or Wilms tumor. [00166]In some embodiments, the present disclosure provides methods of treating a subject in need of treatment by administering to the subject a composition comprising any of the engineered cells described herein. As used, the terms "treat," "treatment," and the like refer generally to obtaining a desired pharmacological and/or physiological effect. That effect is preventive in terms of complete or partial prevention of the disease and/or therapeutic in terms of partial or complete cure of the disease and/or adverse effects resulting from the disease. The term "treatment", as used herein, encompasses any treatment of a disease in a subject (e.g., mammal, e.g., human). Treatment may also refer to the administration of the engineered cells provided herein to a subject that is susceptible to the disease but has not yet been diagnosed as suffering from it, including preventing the disease from occurring; inhibiting disease progression; or reducing the disease (i.e., causing a regression of the disease). Further, treatment may stabilize or reduce undesirable clinical symptoms in subjects (e.g., patients). The cells provided herein populations thereof, or compositions thereof may be administered before, during or after the occurrence of the disease or injury. [00167]In certain embodiments, the subject has a disease, condition, and/or injury that can be treated and/or ameliorated by cell therapy. In some embodiments, the subject in need of cell therapy is a subject having an injury, disease, or condition, thereby causing cell therapy (e.g., therapy in which cellular material is administered to the subject). However, it is contemplated that it is possible to treat, ameliorate and/or reduce the severity of at least one34 WO 2022/093846 PCT/US2021/056689 symptom associated with the injury, disease or condition. In certain embodiments, a subject in need of cell therapy includes, but is not limited to, a bone marrow transplant or stem cell transplant candidate, a subject who has received chemotherapy or radiation therapy, a hyperproliferative disease or cancer (e.g., a hematopoietic system), a subject having or at risk of developing a hyperproliferative disease or cancer), a subject having or at risk of developing a tumor (e.g., solid tumor), viral infection or virus. It is also intended to encompass subjects suffering from or at risk of suffering from a disease associated with an infection. [00168]In some embodiments, the present disclosure provides a composition of the present disclosure along with instructions for use. The instructions for use can be present in the kits as a package insert, in the labeling of the container of the kit or components thereof, or can be in digital form (e.g. on a CD-ROM, via a link on the internet). A kit can include one or more of a genome-targeting nucleic acid, a polynucleotide encoding a genome- targeting nucleic acid, a site-directed polypeptide, and/or a polynucleotide encoding a site- directed polypeptide. Additional components within the kits are also contemplated, for example, buffer (such as reconstituting buffer, stabilizing buffer, diluting buffer), and/or one or more control vectors.

Combination Therapies [00169]In some embodiments, an engineered cells of the present disclosure or composition thereof is administered with at least one additional therapeutic agent. Any suitable additional therapeutic agent may be administered with an engineered cell provided herein, populations thereof, or compositions thereof. In some aspects, the additional therapeutic agent is selected from radiation, an ophthalmologic agent, a cytotoxic agent, a chemotherapeutic agent, a cytostatic agent, an anti-hormonal agent, an immunostimulatory agent, an anti-angiogenic agent, and combinations thereof. [00170]In some embodiments, an engineered cell of the present disclosure or composition thereof is administered with a steroid. The administration of a steroid can prevent or mitigate the risk of a subject receiving the engineered cell(s) or composition thereof having an autoimmune reaction. [00171]The additional therapeutic agent may be administered by any suitable means. In some embodiments, the engineered cells described herein, populations thereof, or compositions thereof and the additional therapeutic agent is administered in the same pharmaceutical composition, e.g. by infusion. In some embodiments, the engineered cells 35 WO 2022/093846 PCT/US2021/056689 described herein and additional therapeutic agent are included in different pharmaceutical compositions. [00172]The pharmaceutical composition may comprise one or more pharmaceutical excipients. Any suitable pharmaceutical excipient may be used, and one of ordinary skill in the art is capable of selecting suitable pharmaceutical excipients. Accordingly, the pharmaceutical excipients provided below are intended to be illustrative, and not limiting. Additional pharmaceutical excipients include, for example, those described in the Handbook of Pharmaceutical Excipients, Rowe el al. (Eds.) 6th Ed. (2009), incorporated by reference in its entirety. [00173]Various modes of administering the additional therapeutic agents are contemplated herein. In some embodiments, the additional therapeutic agent is administered by any suitable mode of administration. Generally, modes of administration include, without limitation, intravitreal, subretinal, suprachoroidal, intraarterial, intradermal, intramuscular, intraperitoneal, intravenous, nasal, parenteral, topical, pulmonary, and subcutaneous routes. [00174]In embodiments where the engineered cells provided herein and the additional therapeutic agent are included in different pharmaceutical compositions, administration of the engineered cells provided herein can occur prior to, simultaneously, and/or following, administration of the additional therapeutic agent.

Additional Embodiments [00175]In some aspects, provided herein are engineered cells, comprising at least one sequence encoding a transgene, wherein the at least one sequence is inserted within a safe harbor locus; wherein the safe harbor locus is at any one or more of the sgRNA target loci selected from: chrl0:33130000-33140000, chr!0:72290000-72300000, chrl 1:128340000- 128350000, chrl 1:65425000-65427000 (NEAT1), chrl5:92830000-92840000, chrl6:11220000-11230000, chr2:87460000-87470000, chr3:186510000-186520000, chr3:59450000-59460000, chr8:127980000-128000000, chr9:7970000-7980000, APRT, B2M, CAPNS1, CBLB, CD2, CD3E, CD3G, CDS, EDF1, FTL, PTEN, PTPN2, PTPN6, PTPRC, PTPRCAP, RPS23, RTRAF, SERF2, SLC38A1, SMAD2, SOCS1, SRP14, SRSF9, SUB1, TET2, TIGIT, TRAC, and TRIM28 [00176]In some embodiments, expression of the at least one sequence encoding the transgene is operatively linked to an endogenous promoter. [00177]In some embodiments, expression of the at least one sequence encoding the transgene is operatively linked to an exogenous promoter.36 WO 2022/093846 PCT/US2021/056689 id="p-178" id="p-178" id="p-178" id="p-178" id="p-178" id="p-178" id="p-178" id="p-178"

[00178]In some embodiments, the target locus is selected from: chrlO:33130000- 33140000, chr!0:72290000-72300000, chrl 1:128340000-128350000, chrl 1:65425000- 65427000 (NEAT1), chrl5:92830000-92840000, chrl6:11220000-11230000, chr2:87460000-87470000, chr3:186510000-186520000, chr3:59450000-59460000, chr8:127980000-128000000, and chr9:7970000-7980000. [00179]In some embodiments, the target locus is chrl 1:128340000-128350000 or chrl 5:92830000-92840000. [00180]In some embodiments, the target locus is a gene selected from: APRT, B2M, CAPNS1, CBLB, CD2, CD3E, CD3G, CDS, EDF1, FTL, PTEN, PTPN2, PTPN6, PTPRC, PTPRCAP, RPS23, RTRAF, SERF2, SLC38A1, SMAD2, S0CS1, SRP14, SRSF9, SUB1, TET2, TIGIT, TRAC, and TRIM28. [00181]In some embodiments, the safe harbor locus is the GS94 or GS102 integration site in Table 4. [00182]In some embodiments, the exogenous promoter is an EFla promoter. [00183]In some embodiments, the engineered cell is a natural killer (NK) cell, an induced pluripotent stem cells (iPSC), a human pluripotent stem cell (HSPC), a T cell or a T cell progenitor. [00184]In some embodiments, the transgene encodes a recombinant protein, a therapeutic agent, or a chimeric antigen receptor (CAR). [00185]In some aspects, provided herein are compositions comprising the engineered cell described herein and a pharmaceutical excipient. [00186]In some aspects, provided herein are guide ribonucleic acids (gRNA) for editing a cell at a safe harbor locus, wherein the gRNA comprises any one of SEQ ID NOS: 1-120. [00187]In some aspects, provided herein are methods of editing a cell having chromosomal DNA, comprising inserting at least one sequence encoding a transgene within a safe harbor locus in the chromosomal DNA of the cell, wherein the safe harbor locus is at any one or more of the sgRNA target loci selected from: chrl 0:33130000-33140000, chrl0:72290000-72300000, chrl 1:128340000-128350000, chrl 1:65425000-654270(NEAT1), chrl5:92830000-92840000, chrl6:11220000-11230000, chr2:87460000- 87470000, chr3:186510000-186520000, chr3:59450000-59460000, chr8:127980000- 128000000, chr9:7970000-7980000, APRT, B2M, CAPNS1, CBLB, CD2, CD3E, CD3G, CDS, EDF1, FTL, PTEN, PTPN2, PTPN6, PTPRC, PTPRCAP, RPS23, RTRAF, SERF2, SLC38A1, SMAD2, SOCS1, SRP14, SRSF9, SUB1, TET2, TIGIT, TRAC, and TRIM2837 WO 2022/093846 PCT/US2021/056689 id="p-188" id="p-188" id="p-188" id="p-188" id="p-188" id="p-188" id="p-188" id="p-188"

[00188]In some embodiments, the target locus is selected from: chrlO:33130000- 33140000, chr!0:72290000-72300000, chrl 1:128340000-128350000, chrl 1:65425000- 65427000 (NEAT1), chrl5:92830000-92840000, chrl6:11220000-11230000, chr2:87460000-87470000, chr3:186510000-186520000, chr3:59450000-59460000, chr8:127980000-128000000, and chr9:7970000-7980000. [00189]In some embodiments, the target locus is chrl 1:128340000-128350000 or chrl 5:92830000-92840000. [00190]In some embodiments, the target locus is a gene selected from: APRT, B2M, CAPNS1, CBLB, CD2, CD3E, CD3G, CDS, EDF1, FTL, PTEN, PTPN2, PTPN6, PTPRC, PTPRCAP, RPS23, RTRAF, SERF2, SLC38A1, SMAD2, S0CS1, SRP14, SRSF9, SUB1, TET2, TIGIT, TRAC, and TRIM28. [00191]In some embodiments, the transgene encodes a recombinant protein, a therapeutic agent, or a chimeric antigen receptor (CAR). [00192]In some embodiments, the at least one sequence comprises an exogenous promoter and the exogenous promoter is operably linked to the transgene. [00193]In some embodiments, the cell is a T cell or T cell progenitor. [00194]In some embodiments, the at least one sequence is inserted using a homology- directed repair or a homology independent targeted insertion. [00195]In some embodiments, the at least one sequence is inserted using one or more guide ribonucleic acids (gRNAs) and one or more Cas9 endonucleases, wherein the one or more gRNAs comprises any one of SEQ ID NOS: 1-120. [00196]In some aspects, provided herein are ex vivo methods of obtaining an engineered cell or population thereof, comprising: obtaining a cell; genetically modifying the cell by inserting at least one sequence encoding a transgene within a safe harbor locus, wherein the safe harbor locus is at any one or more of the sgRNA target loci selected from: chrl0:33130000-33140000, chrl0:72290000-72300000, chrl 1:128340000-128350000, chrl 1:65425000-65427000 (NEAT1), chrl5:92830000-92840000, chrl6:l 1220000- 11230000, chr2:87460000-87470000, chr3:186510000-186520000, chr3:59450000- 59460000, chr8:127980000-128000000, chr9:7970000-7980000, APRT, B2M, CAPNS1, CBLB, CD2, CD3E, CD3G, CDS, EDF1, FTL, PTEN, PTPN2, PTPN6, PTPRC, PTPRCAP, RPS23, RTRAF, SERF2, SLC38A1, SMAD2, SOCS1, SRP14, SRSF9, SUB1, TET2, TIGIT, TRAC, and TRIM28.

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[00197]In some embodiments, obtaining the cell comprises: (i) collecting a tissue sample from a subject, (ii) isolating the cells from the tissue samples, and (iii) culturing the cells in vitro. [00198]In some embodiments, the cell is a stem cell, a natural killer (NK) cell, an induced pluripotent stem cells (iPSC), a human pluripotent stem cell (HSPC), a T cell or a T cell progenitor. [00199]In some embodiments, the at least one sequence is inserted using a homology- directed repair or a homology independent targeted insertion. [00200]In some embodiments, the genetically modifying in step (b) comprises contacting the cell with one or more guide ribonucleic acids (gRNAs), the at least one sequence, and one or more Cas9 endonucleases, wherein the one or more gRNAs and Cas9 endonucleases facilitate the insertion of the at least one sequence into chromosomal DNA within the safe harbor locus and wherein the one or more gRNAs comprises any one of SEQ ID NOS: 1-120. [00201]In some embodiments, the at least one sequence comprises an exogenous promoter and the exogenous promoter is operably linked to the transgene. [00202]In some aspects, provided herein are methods of treating a subject having or at risk of having a disease, comprising administering to the subject an effective amount of the engineered cell described herein. [00203]In some aspects, provided herein are methods of treating a subject having or at risk of having a disease, comprising: conducting the method described herein; and administering to the subject an effective amount of a composition comprising the cell or a population thereof. [00204]In some embodiments, the disease is cancer.

EXAMPLES [00205]The following are examples of methods and compositions of the invention. It is understood that various other embodiments may be practiced, given the general description provided herein. [00206]Below are examples of specific embodiments for carrying out the present invention. The examples are offered for illustrative purposes only, and are not intended to limit the scope of the present invention in any way. Efforts have been made to ensure accuracy with respect to numbers used (e.g., amounts, temperatures, etc.), but some experimental error and deviation should, of course, be allowed for.

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[00207]The practice of the present invention will employ, unless otherwise indicated, conventional methods of protein chemistry, biochemistry, recombinant DNA techniques and pharmacology, within the skill of the art. Such techniques are explained fully in the literature. See, e.g., T.E. Creighton, Proteins: Structures and Molecular Properties (W.H. Freeman and Company, 1993); A.L. Lehninger, Biochemistry (Worth Publishers, Inc., current addition); Sambrook, et al., Molecular Cloning: A Laboratory Manual (2nd Edition, 1989); Methods In Enzymology (S. Colowick and N. Kaplan eds., Academic Press, Inc.);Remington's Pharmaceutical Sciences, 18th Edition (Easton, Pennsylvania: Mack Publishing Company, 1990).

Example 1: Identification of Knock-In Loci in Coding Regions [00208]The objective of the experiments in this set of examples was to identify T-cell knock-in (KI) loci in coding regions outside of the T Cell Receptor Alpha Constant (TRAC) locus. To select candidate loci, the criteria and requirements shown in Table 1 were used.

Table 1:Criteria used for identification of candidate knock-in loci within coding regions Criteria Detailed Requirements Datasets Considered for identification of loci KI efficiency • High expression atd2 (day 2)• Similar expressiondynamics as TRAC (stable expression upon activation)• Accessible chromatin• gRNA editing efficiency • Knock in efficiency data on ~90 genes derived from Roth, T. L., et al. 2019. (Rapid discovery of synthetic DNA sequences to rewrite endogenous T cell circuits. bioRxiv, 604561.)• Bulk RNA-seq data at dO, d2, d3 and d4:■ (i) publicly available data;■ (ii) data derived from Roth, T. L., et al. 2019. (Rapid discovery of synthetic DNA sequences to rewrite endogenous T cell circuits. bioRxiv, 604561.); and■ (iii) internally generated data• Bulk ATAC-seq data at dO, d2, d3 and d4:■ (i) data derived from Roth, T. L., et al. 2019. (Rapid discovery of synthetic DNA sequences to rewrite endogenous T cell circuits. bioRxiv, 604561.); and■ (ii) internally generated data Safety • Does not affect proliferation, cytolytic activity or signaling of T cells• Be careful with tumor suppressors and oncogenes • T cell screening data• Achilles ’ project on cancer cell lines data• Annotated oncogenes and tumor suppressors from TCGA• Annotated !unctions in immune cells WO 2022/093846 PCT/US2021/056689 id="p-209" id="p-209" id="p-209" id="p-209" id="p-209" id="p-209" id="p-209" id="p-209"

[00209]Generally, the requirements for candidate KI loci within the coding regions was that the coding gene is not essential for T cell function or the knock-out of that gene would be beneficial to chimeric antigen receptor therapy (CAR T) functions. [00210]As shown in Table 1, some of the data utilized, for comparison purposes, to identify candidate KI loci was sourced, in part, from Roth, T. L., et al. 2019 (Rapid discovery of synthetic DNA sequences to rewrite endogenous T cell circuits. bioRxiv, 604561), the relevant disclosures of which are herein incorporated by reference in their entirety. A summary of data in the Roth, T.L. et al. paper is shown in FIG. 3. [00211] FIG 4Aand FIG 4Bshow the processed RNA-seq data, showing that samples cluster based on activation status and by cell type. Donor 4 (AKI4) was identified as an outlier, as it clustered differently than the others, and was removed from remaining analysis. The transcript expression data from RNA-seq experiments on the 90 genes cited in the Roth, T.L. et al. paper was correlated to transcript expression data in Roth, T.L. et al. paper. (See FIG. 5Aand FIG. 5B) [00212] FIG. 6shows the process ATAC-seq data, which focused on the 10 kb area around the transcription start site (TSS). Again, donor 4 (AKI4) was identified as an outlier, based on expression profile in both CD4 and CDS cells, and was removed from remaining analysis. The results of the remaining ATAC-seq analysis are shown in FIGS. 7A-8.The data in FIG.7 Afor TSS enrichment scores also indicated that all libraries were high quality.The data on open chromatin regions around the TRAC locus revealed the highest signal near exon rather than exon 1 (FIG. 8). Determination of Knock-In Efficiency: [00213]The KI efficiency results (obtained using the model described infra) based on the donors, 2 gRNA, and 2 replicates/gRNAs from the Roth, T.L. et al. paper are shown in FIG. 9and FIG. 10 [00214]A linear model was built to estimate KI efficiency of approximately 90 genes using RNA-seq and ATAC-seq data. The linear model captured 33% of the variation in the data (i.e. R2=0.33). FIG. 11shows KI efficiency versus day 2 (d2) RNA-seq data, day 4 (d4) RNA seq data, and d2 ATAC data. The linear model was applied to remaining candidate genes to estimate their KI efficiency. [00215]The candidate coding loci were selected by first ranking all genes in the pooled data sets by predicted KI efficiency, using RNA-seq expression data from d2 (day 2). Candidate coding loci were required to be stably expressed during T cell activation (e.g.,41 WO 2022/093846 PCT/US2021/056689 <=2-fold expression change relative to day 0 (dO). The candidate loci also had to be accessible based on ATAC-seq data. Using that selection process/requirements, 16 well- characterized coding genes (with known functions) were selected as candidate genes. The knockout of these 16 would confer a benefit to the function of CAR T cells (e.g. B2M, CDS, SMAD2, PTPRC, CD3E). An additional 12 coding genes with high predicted KI efficiency and no apparent essential function (inert coding genes) were selected as candidate genes. (See Table 2). Table 2:KI Candidate Loci selected Genes with Known Functions Inert Coding Genes B2M (-70%) CD2 SUB1CD3E (-50%) SMAD2 EDF1PTPRC (-50%) SLC38A1 CAPNS1CD3G (-30%) TIGIT SRP14 ןTested in Roth, T.L. et al paper (reported editing efficiency from Roth, T.L. et al paper) SOCS1 RTRAFPTPN2 APRTCBLB PTPRCAPPTEN SRSF9PTPN6 FTLCD5 TRIM28TET2 SERF2TRAC RPS23 Example 2: Identification of Knock-In Loci in Gene Deserts [00216]The criteria for selection of candidate loci in non-coding regions or gene deserts is summarized in Table 3.

Table 3:Criteria used for identification of candidate knock-in loci within non-coding regions Criteria Detailed Requirements Datasets Considered for identification of loci KIefficiency• Accessible chromatin • Bulk ATAC-seq data at dO, d2, d3 and d4:■ (i) data derived from Roth, T. L., et al.2019. (Rapid discovery of synthetic DNA sequences to rewrite endogenous T cell circuits. bioRxiv, 604561.); and■ (ii) internally generated data Safety• >10kb from cancer-related genes or TADS• Ensembl genes WO 2022/093846 PCT/US2021/056689 • >10kb from any miRNA/functional small RNAs• >10kb from any 5' gene end• >10kb from any regulatory regions (ultra-conserved elements, enhancers) • Annotated oncogenes and tumor suppressors from TCGA• Annotated enhancers from Encode and papers id="p-217" id="p-217" id="p-217" id="p-217" id="p-217" id="p-217" id="p-217" id="p-217"

[00217]To select candidate regions within the non-coding regions, the inventors here started by looking in highly accessible regions of the genome (10 kb windows). The most accessible region overlapped with (i) annotated protein coding genes (>50% accessible regions), (ii) pseudogenes and noncoding RNAs (-20% accessible regions), and (iii) enhancer/regulatory regions (-20% accessible regions). The candidate genes were required to be < 10 kb from the coding regions. A few regions that overlapped with long intergenic noncoding RNAs (lincRNAs) but did not have apparent function in T cells were also considered. [00218]Examples of other criteria that have been used in the art for selection of SHSare described, for example in Pellenz, S., el at (2019). New human chromosomal sites with "safe harbor" potential for targeted transgene insertion. Human gene therapy, 30(7), 814-828, the relevant disclosures of which are herein incorporated by reference in their entirety. [00219] FIG. 12is a plot showing the normalized ATAQ SEQ data for a top candidate non-coding region. [00220]Using the above-described selection process/requirement, 11 candidate regions in gene deserts were selected. In total, there were 39 KI candidate loci, including those in coding and non-coding regions that would be evaluated as safe harbor loci (predicted loci).

Example 3: Experimental Evaluation of Predicted Loci [00221] Materials • 120 sgRNAs were ordered from Synthego, 3 sgRNAs per region, and editing efficiency was assessed by next generation sequencings (NGS).■ 87 targeted coding genes■ 33 targeted gene deserts• 189 constructs were synthesized by Genscript■ Homology arm: 450bp each■ eGFP was used as the reporter43 WO 2022/093846 PCT/US2021/056689 ■ Vector b ackb one: pUC 5 7 -Kan b ackb one■ 78 with endogenous promoters■ 111 with EF1 a-HTLV promoter• Constructs were sequence verified by Genscript and majority were internally verified by sequencing. The sgRNA sequences are provided in Table 4 and the construct sequences are provided in Table 5. [00222] Methods [00223] To evaluate the effectiveness of the predicted loci, the following were used: [00224] (87 endogenous constructs + 120 exogenous construct)*2 = 414 wells + Controls=460 [00225] 3 donors, 2 replicates at 3 time points: wkl (d6=day 6), wk3 (d21=day 21) andwk4 (d28=day 28) [00226]Controls [00227]DNA-only (no ribonucleoprotein (RNP)): episomal expression (n=8) [00228]DNA + non-targeting guides + RNP: to check if DNA delivery is more efficient with RNP (n=8) [00229]pMax GFP was measured to check if transfection is ok (n=3). [00230] WT cells with no electroporation [00231] WT cells with electroporation [00232]Controls were spread out across plates. [00233]Cells were electroporated without RNP/HDR to check if cell counting makessense. [00234] 2 more donors were added and changed to 3 replicates at 1 time point: wkl (d6) [00235]FACS panel: GFP, TCR, Zombie [00236]Washed every 3 wells. [00237]The secondary data collected included: RNA-seq data: at dO, d2, and d4 (to determine stable expression) and ATAC-seq data: at d2 (to identify activated cells). The methods used for conducting the RNA-seq and ATAC-seq experiments are in Roth, T. L., et al. 2019. (Rapid discovery of synthetic DNA sequences to rewrite endogenous T cell circuits. bioRxiv, 604561), which is herein incorporated by reference in its entirety. [00238]Automated gating was performed on FACS data, using .fcs files. For constructs with endogenous promoters, all 5 donors and all 3 time points were used. For constructs with EFla promoter, used 3 donors (donors 1-3) and 2 time points (wk3 and wk4).44 WO 2022/093846 PCT/US2021/056689 id="p-239" id="p-239" id="p-239" id="p-239" id="p-239" id="p-239" id="p-239" id="p-239"

[00239]To summarize data, wells with a %KI efficiency (% GFP high cells) <=10% (likely a gating error, experimental error or minimal integration) were removed. Loci were then ranked by median expression among donors and median %KI efficiency among donors. [00240]Loci significance was calculated using robust rank aggregation, which was the methodology used for consistent ranking of loci among donors and time points. Methods for conducting robust rank aggregation are known in the art. (See, for example, Koide, R., et al. (2012). Robust rank aggregation for gene list integration and meta-analysis. Bioinformatics (Oxford, England), 28(4), 573-580, the disclosure of which is herein incorporated by reference in its entirety). [00241] Results [00242]The results from the analysis of controls and experimental groups is shown in FIGS. 13A-25. [00243]The results of the pmax_GFP control experiments revealed that donor 5 had significantly higher cell count than other donors. Generally, the GFPhigh readings decreased overtime, as expected. (FIGS. 13A and 13B). [00244]Experiments to analyze non-targeting controls for changes in episomal GFP expression, revealed that episomal GFP expression decreased to less than 0.05 over time. (FIGS. 14A and 14B) Some of the outliers were attributed to gating errors, which were most severe in donor 3. WT control experiments also exhibited <0.05 GFP high readings, as expected (FIG. 15). [00245]As shown in FIG. 16 and FIG. 17, there was a more consistent trend among donors when using sgRNA5 to target the B2M safe harbor locus. [00246]A comparison of GFP expression trends between sgRNA79 and sgRNA83 for TRAC insertion and expression with an endogenous reporter revealed that donor 2 trends were different between sgRNA79 and sgRNA83, while donor 4 trends were the same (FIG. and FIG. 22). Some potential reasons for the observed variation between replicates and donors include: [00247] (1) manual handling of a large number of plates (e.g., FIG. 26): [00248]Edge effects [00249]Electroporation errors [00250] (2) Inherent differences among donors (e.g., FIG. 27): [00251]There were consistent differences with certain wells throughput the assay (spanning multiple weeks)45 WO 2022/093846 PCT/US2021/056689 id="p-252" id="p-252" id="p-252" id="p-252" id="p-252" id="p-252" id="p-252" id="p-252"

[00252]There were variable cell numbers between donors [00253] (3) Gating errors (e.g. FIG. 28): [00254] 1 peak vs >2 peaks in GFP signals Example 4: Ranking Loci by Expression and KI Efficiency [00255]The loci were ranked based on mean florescence intensity (MFI) of reporter gene, GFP, and KI efficiency. [00256] FIG. 29shows GFP MFI and KI efficiency for all significant loci having endogenous promoters. The B2M locus reported the highest GFP MFI. The TRAC locus was among the top 10 MFI. The highest GFP MFI readings were reported in week 1 and reduced slightly in weeks 3 and 4. The results also showed most top loci have more than 1 sgRNA. With regard to KI efficiency, the SOCS1 locus reported the highest KI efficiency. Overall, KI efficiency showed greater variation among donors than GFP MFI. [00257] FIG. 30shows GFP MFI and KI efficiency for all significant loci having exogenous promoters (e.g. EFla promoters). The TRAC locus reported the highest GFP MFI. There was comparable expression between weeks 3 and 4. The results also showed most top loci have more than 1 sgRNA. With regard to KI efficiency, the SOCS1 locus reported the highest KI efficiency. Overall, KI efficiency showed less variation when driven by the exogenous promoters than when driven by endogenous promoters. [00258] FIGS. 31A, 31B, and 31Cshow GFP MFI and KI efficiency for all significant loci having endogenous and exogenous (e.g., EFla) promoters. The results showed that expression driven by EFla promoters is about 10 X higher than endogenous promoters (FIG. 31 A).With regard to KI efficiency, the SOCS1 locus reported the highest KI efficiency. At weeks 3 and 4, KI efficiency was higher when driven by the exogenous promoters than when driven by endogenous promoters.

Example 5: Evaluation of TCR expression in candidate noncoding sites [00259]This experiment was conducted to identify target loci and integration sites that enable high transgene expression without disrupting the TCR. Some gene deserts (e.g. gene deserts 2, 3, 5, and 6) were identified as having high transgene expression (FIG. 32A). [00260]To evaluate and identify preferred knock-in sites, TCR expression was measured following circuit cassette knock in of PrimeR (Prime Receptor (Myc)). Myc denotes an N- terminal Myc epitope tag to facilate detection of surface expressed primer receptor. Briefly, CD3-CD28 Dynabead-activated T cells were electroporated with sgRNA/Cas9 RNPs WO 2022/093846 PCT/US2021/056689 targeting the indicated sites (see FIG. 32B and 33A),as well as HDRTs with homology arms directing HDR-mediated integration into the indicated sites. At day 6 post-electroporation, cells were stained with anti-TCRalpha/beta and anti-myc antibodies and analyzed on an Attune NxT flow cytometer. As shown in FIG. 32B,the TCR expression was maintained at GS94 and GS102 candidate integration (knock-in) sites. Only 2/3 of the cells that had circuit cassette knock in of PrimeR at GS79 (TRAC) locus maintatined TCR expression. These results indicated that the GS94 and GS102 sites showed better potential for TCR stimulation. [00261]The percentage of cells showing effective knock-in (based on measurements of PrimeR) was 36% ± 4% when using the GS94 integration site, as compared to 32% ± 5% when using the TRAC integration site. These results revealed integration sites, including GS94, that supported reproducibly high circuit cassette knockin rates. See FIG. 33A.

Example 6: Evaluation of GS94 circuit expression and function [00262]GS94 is a candidate integration site located on chromosome H’s distal q arm. It is within 180-350kb of the promoters for ETS1 and FLU (FIG. 33B),however that is considered low-risk for integration vector gene therapy. The circuit expression and function potential of the GS94 gene was evaluated. [00263]T cells underwent circuit cassette integration with PrimeR at GS79 (TRAC) integration site and GS94 integration site. The cells were cocultured with K562 C19 cells for hours and then the PrimeR induced CAR MFI was compared to the PrimeR MFI. [00264]Briefly, T cells generated as described in the Example above were cocultured with K562 CD19+/MSLN- cells at day 7 post-electroporation. MSLN (mesothelin) is a gene that is overexpressed in human pancreatic cancer. Cells were then stained with anti-FLAG antibody h post initiation of coculture and analyzed on an Attune NxT flow cytometer. The results revealed that GS94 yields superior CAR induction with high prime R expression following the 48-hour coculture with the K562 C19 cells. See FIG. 34A. GS94 resulted in prime antigen-dependent CAR expression that was approximately two-fold higher than the expression in several other candidate integration sites as well as the TRAC integration site. Additionally, on average, the prime receptor surface expression level was no less than 50% of expression level when using the TRAC integration site. Cytotoxicity and Cytokine Secretion [00265]To evaluate the effect of the candidate integration site on cytotoxicity and cytokine secretion, T cells that had undergone circuit cassette integration with PrimeR at GS79 (TRAC) integration site and GS94 integration site were cocultured with K547 WO 2022/093846 PCT/US2021/056689 C19/MSLN cells for 48 hours. MSLN is a gene that is overexpressed in human pancreatic cancer. The cells were treated at a 1:1 effectortarget cell ratio (1:1 E:T)). Briefly, T cells generated as described above were cocultured with K562 CD19+/MSLN+ cells at day 7 post- electroporation. 48h post initiation of coculture, supernatants were collected and analyzed via Luminex for cytokine levels. The cytokines measure were IL-2, INFg, and TNF. Cytotoxicity was analyzed by measuring luciferase activity of remaining target cells after 48h. Each of the data points in FIG. 34B represent two replicates and the lines represent the range of cytotoxicity for the replicates. As shown in FIG. 34B, the GS94 integration sites resulted in superior cycotoxic ability and cytokine secretion following the 48-hour coculture with K5C19/MSLN cells. Prime-independent cytotoxicity [00266]To compare the effect of the candidate integration site on cytotoxicity versus prime-independent cytotoxicity, T cells that had undergone circuit cassette integration with PrimeR at GS79 (TRAC) integration site and GS94 integration site were cocultured with K562 CD19+/MSLN+ cells or K562 CD19-/MSLN+ cells ("K562_MSLN") at day 7 post- electroporation for 48 hours. 0.3, 1.0, and 3.0 E:T cell ratios were tested. See FIG. 35A and FIG. 35B. At 48h post initiation of coculture, cytotoxicity was analyzed by measuring luciferase activity of remaining target cells As shown in FIG. 35B, the GS94 integration site resulted in equivalent cytotoxic potential to the TRAC integration site and there was no prime-independent cytotoxicity. Prime-independent cytokine section [00267]To compare the effect of the candidate integration site on cytoxicity versus prime- independent cytotoxicity, T cells that had undergone circuit cassette integration with PrimeR at GS79 (TRAC) integration site and GS94 integration site, generated as described above, were cocultured with K562 CD19+/MSLN+ cells. A group that had target cells only (E:T = 0; Targets only) was compared to a group with an E:T cell ratio of 1. Following the 48 h coculture with the K562 CD19++/MSLN+ cells, supernatant was collected and analyzed via Luminex for cytokine levels to measure secretion of IL-2, INFg and TNF cytokines. See FIG. 36A and FIG. 36B. As shown in FIG. 36B, the GS94 integration site resulted in equivalent cytokine secretion to the TRAC integration site and and there was no prime-independent secretion of IL-2, INFg or TNF. Prime-independent CAR expression WO 2022/093846 PCT/US2021/056689 id="p-268" id="p-268" id="p-268" id="p-268" id="p-268" id="p-268" id="p-268" id="p-268"

[00268]To evaluate the effect of the candidate integration site on prime-independent CAR expression, T cells that had undergone circuit cassette integration with PrimeR at GS(TRAC) integration site, GS94 integration site, and GS102 integration site were cultured in vitro for 32 days. The cells were treated with repetitive CD3/CD28 stimulation at days 5, 12, and 28 of the experiment. On Day 16, the cells were evaluated for CAR expression using a flow cytometry assay. As shown in FIG. 37,T cell activation through TCR did not result in prime R-independent CAR expression from circuit cassette integration at the candidate integration sites. [00269]T cells generated as described above were cultured in 96-well plates, with T cell growth medium being exchanged every 2 days. At days 5, 12, 19 and 28, T cells were stimulated with 1:1 CD3/CD28 Dynabeads. Cells were analyzed for PrimeR expression by myc epitope tag staining, and for CAR expression by FLAG epitope tag staining at the indicated time points. Flow analysis was performed on an Attune NxT flow cytometer.

Example 7: Evaluating stability of prime receptor expression over several weeks [00270]To evaluate the effect of the candidate integration sites on stable (sustained) expression of PrimeR, T cells that had undergone circuit cassette integration with PrimeR at the integration sites indicated in FIG. 38were cultured in vitro for 32 days. Briefly, T cells generated as described above were cultured in 96-well plates, with T cell growth medium being exchanged every 2 days. At days 5, 12, 19 and 28, T cells were stimulated with 1:CD3/CD28 Dynabeads repetitive stimulation. Flow cytometry assays were run on days and 32 using an Attune NxT flow cytometer. The cells were analyzed for PrimeR expression by myc epitope tag staining. As shown in FIGS. 38A and 38B,the GS94 integration site resulted in stable PrimeR expression over at least a 4-week period.

Example 8: Evaluation of on-target editing efficiency [00271]To evaluate the on-target editing efficiency of candidate knock-in sites, iGUIDE- Seq assay was used. The methods used for conducting the iGUIDE-Seq assay are illustrated in FIG. 39Aand provided in Nobles et al., Genome Biology (2019), which is hereby incorporated by reference in its entitrety. As shown in FIG. 39B, the GS94 integration site had the highest on-target editing efficiency of the evaluated candidate integration sites. As shown in FIG. 39C, GS94 resulted in no putative off-target editing as observed with two donors.

WO 2022/093846 PCT/US2021/056689 Example 9: Evaluation of GS94 knock-in Methods [00272] Elevation prediction:Computational predictions of potential off-target sites from (gs94) were performed using Elevation-search (algorithm described in Listgarten et al. 2018. Prediction of off-target activities for the end-to-end design of CRISPR guide RNAs. Nat Biomed Engr 2,37-48; software obtained from https://github.com/Microsoft/Elevation). All sites identified by Elevation-search were subjected to analysis using rhAmp-seq. [00273] rhAmpSeq:49 candidate off-target sites for GS94 identified by iGUIDE or the Elevation prediction algorithm and the GS94 target site were characterized by rhAmpSeq (Integrated DNA Technologies, Inc.). This targeted amplification enables NGS-based quantification of the editing occurring at numerous sites simultaneously. Genomic DNA from T cells from at least 2 donors that had been treated singly with each of the following 7 guides: GS84, GS94, GS95, GS96, GS102, GS108, and GS138 was isolated with the GenFind VDNA purification system (Beckman Coulter). Two separate rhAmpSeq amplification pools were used to cover the 50 loci, the procedure was performed as recommended by Integrated DNA Technologies for each of the samples. The rhAmpSeq libraries were sequenced on a MiniSeq with a Mid Output Kit (300-cycles) (Illumina). The CRISPRess02 algorithm (https://github.com/pinellolab/CRISPResso2) was used to determine the percentage of insertions and deletions at each of the amplified loci. Statistical significance (FDR-adjusted p-value < 0.001) using a chi-squared test was only observed at the GS94 site. [00274] RNA-seq:To evaluate changes induced by GS94 integration at the transcriptional level, a CD19/MSLN circuit was integrated at the GS79 (TRAC), GS94, and GS1integration sites. On day 6 post-integration, led edited cells were sorted using a BD FACSAria based on transgene expression. RNA was isolated from sorted T cells with the RNeasy kit (Qiagen). Purified RNA was converted into an NGS library using the TruSeq RNA Library Prep Kit v2 (Illumina). Libraries were sequenced on either the NovaSeq 60or NextSeq 550 instruments (Illumina). The STAR 2.7.3a aligner (Dobin A. et al.Bioinformatics. 2013. 29:15-21) was used to align the RNA-seq data against the reference human GRCh38 transcriptome and to obtain gene-level read counts. edgeR (Robinson MD et al. Bioinformatics. 2010. 26: 139-140) was used to compute differential expression, combining data across both donors. The only genes within 300Kb of the GS94 site, ETS1 and FLU, were not differentially expressed in cells with integration at the GS94 integration site compared to cells with integration at any of the other two loci. At an FDR-adjusted p-value WO 2022/093846 PCT/US2021/056689 cutoff of 0.01, the number of differentially expressed genes was minimal (<100 genes genome-wide). [00275] Cytokine-independent growth assay:To evaluate the safety of the primary T cells with GS94 locus KI, cytokine-independent growth assay was performed to evaluate the potential for oncogenic transformation. Briefly, primary human T cells that had undergone CD19/MSLN circuit cassette integration at GS94 locus were thawed and recovered overnight. IxlO6 cells were then seeded in one well of a 24 well-GRex plate, culturing for 5 days in the medium with or without cytokines. Cell number and viability were recorded at days 0, 3 and 5. As a positive control, IxlO6 Jurkat cells were cultured in the medium without cytokines in parallel. As shown in FIG. 43,while GS94 KI T cells maintained good viability and total cell count when cultured with cytokine, the viability of GS94 KI T cells drastically decreased over the course of 5 days when cultured without cytokine and there was no viable cell left on day 5. The positive control Jurkat cells maintained good viability and expansion without cytokine throughout the assay. Taken together, this data shows that GS94 edited primary human T cells still depend on exogenous cytokine for growth, survival and expansion, therefore, there is no concern for cellular transformation. Results [00276]The specificity of CRISPR reagents (e.g. SpCas9 complexed with sgRNA) targeting candidate loci including GS94 was evaluated by iGUIDE-seq (FIG. 40).GS94- targeting CRISPR RNP showed the highest percentage of iGUIDE-seq oligo cassette trapping events of all candidates evaluated, and the control sgRNA sequences from the iGUIDE-seq paper showed similar specificities to what was reported in the original publication, suggesting that the assay performed as expected. [00277]Putative off-target sites were taken from the iGUIDE-seq output, which already suggested that the putative sites were spurious. Additional target sites were predicted by a computational approach (Elevation software package). rhAmp-seq was used to prepare high- throughput sequencing libraries for each of the putative off-target sites, and the method was applied to DNA samples from T cells electroporated with CRISPR RNPs targeting the candidate target sites. The resulting NGS data were processed with CRISPRess02 software, and the frequency of insertions and deletions (indels) was taken as indication of CRISPR cleavage activity, as is common in the field. T cells electroporated with GS94-targeting CRISPR RNP showed no greater frequency of indels at the set of putative off-target sites than T cells treated with CRISPR RNP targeting other sites, consistent with the GS94-targeting51 WO 2022/093846 PCT/US2021/056689 CRISPR RNP having no consequential or detectable off-target activity, and therefore being the most specific out of the set evaluated (FIG. 41). [00278]Potential effects of transgene integration at the GS94 site on the regulation of the T cell transcriptome were evaluated by knocking in a large cassette to the site, growing T cells for several days, sorting cells expressing the transgene within the cassette, and then collecting RNA from the cells. RNA-seq libraries were prepared and sequenced, and analysis of the resulting Illumina sequencing data revealed no biologically or statistically significant differences in expression of any genes within 300kb of the GS94 site in cells with integrations at GS94 compared to cells with integration at TRAC or the GS102 sites (FIG. 42).Furthermore, other gene expression differences that reached statistical significance were minimal in number and in effect size, consistent with them being noise in the comparison. [00279]To assess whether transgene integration at GS94 could confer a transformed phenotype, cells with integrations at the GS94 site were cultured with and without cytokines in vitro. Cells remained alive and viable with cytokine addition, but died without cytokine supplementation and lost their viability (FIG. 43).The positive control Jurkat cells remained viable and proliferated. Overall, this indicates that integration of a transgene at GS94 does not confer capacity for cytokine-independent growth, which is a hallmark of T cell transformation.

Example 10: In vivo Insertion of a CAR expressing cassette [00280]In vivo efficacy of T cells with a transgene cassette expressing a CAR recognizing a tumor antigen, or a CAR recognizing a tumor antigen under control of a priming receptor recognizing an antigen in the anatomical vicinity of the tumor, is assessed against human tumor cells such as K562 engineered to express the CAR antigen or to express antigens recognized by both the priming receptor and the CAR. Tumor cells (e.g. Ie6) are subcutaneously injected into the flank of NSG mice (Jackson Laboratories). Tumor growth is assessed by dimensional measurement by calipers every 2-4 days. When the tumor volume reaches -100 cubic mm, mice are intravenously injected with 5e6 T cells with a CAR or prime-CAR circuit cassette integrated at a specific site by CRISPR-mediated insertion, or with T cells engineered with CRISPR RNP alone, or with PBS alone as a sham injection. Tumor growth is monitored and mice are euthanized when tumor volume reaches 2000 cubic mm. Peripheral blood is bled from mice through a retro-orbital procedure, and flow cytometry and/or ddPCR is used to observe engineered T cell expansion over time. At time of sacrifice, spleen, blood, tumor and/or other tissue is analyzed via flow cytometry, ddPCR, 52 WO 2022/093846 PCT/US2021/056689 and/or immunohistochemistry for the presence of engineered T cells. The results demonstrate that T cells engineered with cassette integration at one of the defined genomic loci lead to tumor regression and clearance in injected mice as compared to T cells without cassette integration, and that engineered T cells are detectable in the peripheral blood and tissues of injected mice.

Example 11: Evaluation of non-viral insertion of a large 8.3kb expression cassette in GS94 [00281]Next, an 8.3 kb insert was inserted into a T cell at the GS94 safe harbor loci using materials/methods as previously described. A diagram of the cassette is provided in FIG. 44. [00282]Construct generation [00283]To generate plasmid constructs for knock-in, synthetic DNA was ordered from Twist, IDT and GENEWIZ and assembled via Gibson Assembly and Golden Gate Assembly. Plasmids contained homology arms homologous to sequences flanking the CRISPR target sites in the genome of 1.2kb or 450 bp in length. [00284]T cell engineering [00285]T-cells were enriched from peripheral blood mononuclear cells (PBMCs) obtained from normal donor Leukopaks (STEMCELL Technologies) using Lymphoprep (STEMCELL Technologies) and the EasySep Human T-Cell Isolation Kit (STEMCELL Technologies). T- cells were subsequently activated with CD3/CD28 Dynabeads at 1:1 bead to cell ratio (ThermoFisher, 40203D) in TexMACS medium (Miltenyi 130-197-196) supplemented with 3% human AB serum (Gemini Bio) and 12.5 ng/ml human IL-7 and IL-15 (Miltenyi premium grade) and cultured at 37°C, 5% CO2 for 48 hours before electroporation. [00286]CRISPR RNP were prepared by combining 120 pM sgRNA (Synthego) targeting DNA sequence GAGCCATGCTTGGCTTACGA (GS94, SEQ ID NO: 94), 62.5 pM sNLS- SpCas9-sNLS (Aldevron) and P3 buffer (Lonza) at a volume ratio of 5:1:3:6, and incubated for 15 minutes at room temperature. An optimized amount of plasmid DNA, determined by dose titration experiments (ranging from 0.5-3 micrograms) was mixed with 3.5 pl of RNP. T-cells were counted, debeaded, centrifuged at 90 X G for 10 minutes and resuspended at 10A6 cells/14.5 pl of P3 with supplement added (Lonza). 14.5 pl of T-cell suspension was added to the DNA/RNP mixture, transferred to Lonza 384-well nucleocuvette plate, and pulsed in a Lonza HT Nucleofector System with code EH-115. Cells were allowed to rest for minutes at room temperature before transfer to 96-well plates (Sarstedt) in TexMACS medium supplemented with 12.5 ng/ml human IL-7 and IL-15 (Miltenyi premium grade).

WO 2022/093846 PCT/US2021/056689 id="p-287" id="p-287" id="p-287" id="p-287" id="p-287" id="p-287" id="p-287" id="p-287"

[00287]Transgene expression was detected by staining with anti-Myc antibody (Cell Signaling Technology clone 9B11) and anti-Flag antibody (RnD systems, clone 1042E) and analyzed on an Attune NxT Flow Cytometer. Other antibodies used were live/dead Fixable Near-IR (Thermo Fisher), TCRalpha/beta antibody (BioLegend clone IP26), CD4 antibody (BioLegend clone RPA-T4), CDS antibody (BioLegend clone SKI). [00288]Priming receptor induction [00289]To assess functional activity of the transgene (ie. synthetic circuit), edited T cells were co-cultured with target cell line expressing priming antigen at 1:1 E:T ratio, and incubated for 24hrs. T cells were harvested and stained with anti-Myc and anti-Flag antibodies to assess for Priming Receptor and CAR expression, respectively. [00290]To assess whether the 8.3kb transgene integration at GS94 resulted in functional knock-in, cells were cultured with parental K562 cells and K562 cells expressing the cognate priming antigen at a 1:1 E:T cell ratio. Cells were assayed by flow cytometry after 48 hours as previously described. K562 cells with priming antigen induced CAR expression, while control parental K562 cells did not (FIG. 45).Overall, this indicates that the Priming Receptor induced CAR expression after insertion of a 8.3kb transgene circuit. Thus, insertion of the 8.3 kb transgene circuit resulted in expression of multiple functional genes.

Example 12: T cell differentiation post editing [00291] Methods [00292]Two donor T cells edited as described above with a priming receptor and CAR synthetic circuit were phenotypically profiled with cell surface T cell subset markers by flow cytometry. Resting T cells were taken from in vitro culture conditions, rinsed with PBS prior to staining with Zombie-Aqua viability dye, CD4, CD8, CD45RA, CCR7 and CD27 with FMOs used as controls for gating and analyzed with an Attune NxT. In FlowJo, single, viable lymphocytes were selected by SSC and FSC and subset profiling by a combination of CCR7, CD27, CD45RA were used to identify Naive- or stem cell memory- (Tn/Tscm: CD45RA+CCR7+CD27+), central memory- (Tcm: CD45RA-CCR7+CD27+), effector memory- (Tem: CD45RA-CCR7-CD27-), or terminal effector- (Tte: CD45RA+CCR7-CD27- ) T cells on CD4+ and CD8+ subpopulations. [00293] Results [00294]The non-viral editing generated a less differentiated T cell product (FIG. 46).In both donors, the non-viral editing did not contribute to an expansion of terminally differentiated T cells, as the major subset of T cells in both subpopulations retained positive 54 WO 2022/093846 PCT/US2021/056689 expression of CD45RA and CCR7. (FIG. 46).This suggests that the edited T cells contain the capacity to expand, survive and persist in vivo.

References [00295]Eyquem, J., Mansilla-Soto, J., Giavridis, T., van der Stegen, S. J., Hamieh, M., Cunanan, K. M., ... & Sadelain, M. (2017). Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature, 543(1643), 113-117. [00296]Sadelain, M., Papapetrou, E. P., & Bushman, F. D. (2012). Safe harbours for the integration of new DNA in the human genome. Nature reviews Cancer, 12(1), 51-58. [00297]Irion, S.,Luche, EL, Gadue, P., Fehling, H. J., Kennedy, M., & Keller, G. (2007). Identification and targeting of the ROSA26 locus in human embryonic stem cells. Nature biotechnology, 25(12), 1477-1482. [00298]Pellenz, S., Phelps, M., Tang, W., Hovde, B. T., Sinit, R. B., Fu, W., ... & Monnat Jr, R. J. (2019). New human chromosomal sites with "safe harbor" potential for targeted transgene insertion. Human gene therapy, 30(1), 814-828. [00299]Roth, T. L., Li, P. J., Nies, J. F., Yu, R., Nguyen, M. L., Lee, Y., ... & Nguyen, D.N. (2019). Rapid discovery of synthetic DNA sequences to rewrite endogenous T cell circuits. bioRxiv, 604561.

TABLE 4:SGRNA SEQUENCES USED FOR EVALUATION OF PREDICTED LOCI sgRNA ID sgRNA Sequence sgRNA_start_coor GRCH38 sgRNA Target Loci Integra tion Site Median (% Modified), summarize d from 2 donors, 2 primersets sgRNA_ GCACCTGAATACCACGCCTG (SEQ. ID NO:1) chrl6:88811818 APRT APRT79.28sgRNA_ CGCCTGCGATGTAGTCGATG (SEQ ID NO:2) chrl6:88811551 APRT APRT78.60sgRNA_ CAGGACGGGCGAGATGTCCC (SEQ ID NO:3) chrl6:88811640 APRT APRT85.25sgRNA_ CTGAATCTTTGGAGTACCTG (SEQ ID NO:4) chrl5:44715425 B2M B2M78.51sgRNA_ GGCCACGGAGCGAGACATCT (SEQ ID NO:5) chrl5:44711550 B2M B2M94.75sgRNA_AAGTCAACTTCAATGTCGGA (SEQ ID NO:6) chrl5:44715515 B2M B2M70.97sgRNA_ GCTTGGAGGCCTGATCAGCG (SEQ ID NO:7) chrl9:36141111 CAPNS1CAP NS 89.34 WO 2022/093846 PCT/US2021/056689 sgRNA_ CTTATCTCTTCGCAGCGAGG (SEQID N0:8) chrl9:36142301 CAPNS1CAP NS 91.09sgRNA_ CACACATTACTCCAACATTG (SEQID N0:9) chrl9:36142676 CAPNS1CAP NS 71.98sgRNA_ TTCCGCAAAATAGAGCCCCA (SEQID NO:10) chr3:105746019 CBLB CBLB91.55sgRNA_ TGCACAGAACTATCGTACCA (SEQID NO:11) chr3:105751622 CBLB CBLB91.43sgRNA_ GCAATAAGACTCTTTAAAGA (SEQID N0:12) chr3:105853470 CBLB CBLB76.18sgRNA_ CAAAGAGATTACGAATGCCT(SEQID N0:13) chrl:116754658 CD2 CD289.80sgRNA_ CAAGGCACCCCAGGTTTCCA(SEQID N0:14) chrl:116754663 CD2 CD292.70sgRNA_ TTACGAATGCCTTGGAAACC (SEQID N0:15) chrl:116754666 CD2 CD292.82sgRNA_ CAGAGACGCATCTGACCCTC (SEQID N0:16) chrll:118315540 CD3E CD3E90.96sgRNA_ CATGCAGTTCTCACACACTG (SEQID N0:17) chrll:118313715 CD3E CD3E87.47sgRNA_ GTGTGAGAACTGCATGGAGA(SEQID N0:18) chrll:118313715 CD3E CD3E86.65sgRNA_ TCTCATTTCAGGAAACCACT (SEQID N0:19) chrll:118349748 CD3G CD3G87.24sgRNA_ AGTCATACACCTTAACCAAG (SEQID NQ:20) chrll:118349754 CD3G CD3G87.99sgRNA_ TTCAAGGAAACCAGTTGAGG (SEQID N0:21) chrll:118352458 CD3G CD3G86.55sgRNA_ GAGCCTTGCCTGGAAATCTG (SEQID NO:22) chrll:61118177 CDS CDS84.03sgRNA_ AAGCGTCAAAAGTCTGCCAG (SEQID NO:23) chrll:61118324 CDS CDS89.19sgRNA_ CGTTCCAACTCGAAGTGCCA (SEQID NO: 24) chrll:61118121 CDS CDS83.11sgRNA_ GAGCGACTGGGACACGGTGA (SEQID NO:25) chr9:136866246 EDF1 EDF188.84sgRNA_ GCTGCGCAAGAAGGGCCCTA (SEQID NO:26) chr9:136866211 EDF1 EDF191.04sgRNA_ TTGTTCTGGCCAGCAGCCCC (SEQID NO: 27) chr9:136863433 EDF1 EDF185.98sgRNA_ CTTCCAGAGCCACATCATCG (SEQID NO:28) chrl9:48965791 FTL FTL93.10sgRNA_ GGGACTCACCAGAGAGAGGT (SEQID NO:29) chrl9:48965601 FTL FTL88.86sgRNA_ CGGTCGAAATAGAAGCCCTA (SEQID NQ:30) chrl9:48965770 FTL FTL93.14sgRNA_ AAAAGGATATTGTGCAACTG (SEQID NO:31) chrl0:87933015 PTEN PTEN92.37sgRNA_ TGTGCATATTTATTACATCG (SEQID NO:32) chrl0:87933183 PTEN PTEN90.64sgRNA_ TTTGTGAAGATCTTGACCAA (SEQID NO:33) chrl0:87933087 PTEN PTEN85.36 WO 2022/093846 PCT/US2021/056689 sgRNA_TGTCATGCTGAACCGCATTG (SEQID NO:34) chr!8:12830972 PTPN2 PTPN287.94sgRNA_CCACTCTATGAGGATAGTCA (SEQID NO:35) chr!8:12859219 PTPN2 PTPN292.45sgRNA_ TTGACATAGAAGAGGCACAA (SEQID NO:36) chr!8:12836828 PTPN2 PTPN293.96sgRNA_ GAGTACTACACTCAGCAGCA (SEQID NO:37) chr!2:6952098 PTPN6 PTPN689.61sgRNA_ TCACGCACAAGAAACGTCCA (SEQID NO:38) chrl2:6954872 PTPN6 PTPN682.74sgRNA_ AGGTCTCGGTGAAACCACCT (SEQID NO:39) chrl2:6951610 PTPN6 PTPN691.27sgRNA_ AGCATTATCCAAAGAGTCCG (SEQID NQ:40) chrl:198696873 PTPRC PTPRC88.88sgRNA_ ATATTAA 1 1C1 1ACCAGTGG(SEQID N0:41) chrl:198692370 PTPRC PTPRC88.95sgRNA_ AGCTTTAAATCAAGGTTCAT (SEQID NO:42) chrl:198756176 PTPRC PTPRC96.89sgRNA_ ATCCCGAGCCCTAAGGTGCA (SEQID NO:43) chrll:67436325 PTPRCAPPTPRCAP84.08sgRNA_GGCAGCGCGGAGGACAGCGT (SEQID NO:44) chrll:67436285 PTPRCAPPTPRCAP97.74sgRNA_ CTCAGGGGGCTACTACCACC (SEQID NO:45) chrll:67436170 PTPRCAPPTPRCAP91.50sgRNA_ GTCACCGACGAGACCAGAAG (SEQID NO:46) chr5:82277810 RPS23 RPS2379.40sgRNA_ GTCGTGGACTTCGTACTGCT (SEQID NO:47) chr5:82277843 RPS23 RPS2383.07sgRNA_ TAAHillAGGCAAGTGTCG (SEQID NO:48) chr5:82277860 RPS23 RPS2361.94sgRNA_ TTAGCTGTTAGACTTGAATA (SEQID NO:49) chrl4:51993810 RTRAF RTRAF85.50sgRNA_ CGAGAGCCGTCAACTTGCGT (SEQID NQ:50) chrl4:51989652 RTRAF RTRAF85.64sgRNA_ CGGCTTCAACTGCAAAGGTG(SEQID N0:51) chr!4:51989700 RTRAF RTRAF88.77sgRNA_ TATGAAAAAGCAGAGCGACT (SEQID NO:52) chrl5:43793025 SERF2 SERF289.61sgRNA_TCTGGCGGGCGAGCTCACGC (SEQID NO:53) chr!5:43792989 SERF2 SERF286.73sgRNA_ CTCACGCTGGTTACCGCCTA (SEQID NO:54) chrl5:43792977 SERF2 SERF280.57sgRNA_ AAAGATTACGAACTTCCCTG (SEQID NO:55) chrl2:46207559 SLC38A1SLC38A92.24sgRNA_ GTTAAAAACAGACATGCCTA (SEQID NO:56) chrl2:46229232 SLC38A1SLC38A91.51sgRNA_ ATGCCTAAGGAGGTTGTACC (SEQID NO:57) chrl2:46229246 SLC38A1SLC38A79.48sgRNA_ CTCCAGGTATCCCATCGAAA (SEQID NO:58) chr!8:47869418 SMAD2 SMAD279.53sgRNA_ CACCAAATACGATAGATCAG (SEQID NO:59) chr!8:47870532 SMAD2 SMAD286.61 WO 2022/093846 PCT/US2021/056689 sgRNA_ TGGCGGCGTGAATGGCAAGA (SEQID NO:60) chr!8:47896729 SMAD2 SMAD282.91sgRNA_ TAGGATGGTAGCACACAACC (SEQID N0:61) chrl6:11255478 S0CS1 SOCS192.25sgRNA_ CAGCAGCAGAGCCCCGACGG (SEQID NO:62) chrl6:11255432 S0CS1 SOCS183.79sgRNA_ CGGCGTGCGAACGGAATGTG (SEQID NO:63) chrl6:11255296 S0CS1 SOCS184.24sgRNA_ TATAGACGCTGCCCGACGTC (SEQID NO:64) chrl5:40038895 SRP14 SRP1495.12sgRNA_ TCCAAAGAAGGGTACTGTGG (SEQID NO:65) chrl5:40038368 SRP14 SRP1492.14sgRNA_ ACAGTACCCTTCTTTGGAAT (SEQID NO:66) chrl5:40038358 SRP14 SRP1465.82sgRNA_ GCGACGGGCGCATCTACGTG (SEQID NO:67) chrl2:120469572 SRSF9 SRSF983.68sgRNA_ CCCGACCTCCATAAGTCCTG (SEQID NO:68) chrl2:120465700 SRSF9 SRSF992.56sgRNA_ GGGGTCCTCGAAGCGCACGA (SEQID NO:69) chrl2:120469426 SRSF9 SRSF989.94sgRNA_ TGCTCTGTTTAGAAGATGAC (SEQID NQ:70) chr5:32591641 SUB1 SUB179.36sgRNA_ ATATTCTTTTCTAGTTAAAG (SEQID N0:71) chr5:32591566 SUB1 SUB170.93sgRNA_ CCTGTAAAGAAACAAAAGAC (SEQID NO:72) chr5:32591614 SUB1 SUB193.66sgRNA_ TGGAGAAAGACGTAACTTCG (SEQID NO:73) chr4:105234315 TET2 TET283.53sgRNA_ TCTGCCCTGAGGTATGCGAT (SEQID NO:74) chr4:105234747 TET2 TET290.97sgRNA_ ATTCCGCTTGGTGAAAACGA (SEQID NO:75) chr4:105235656 TET2 TET289.62sgRNA_ CAGGCACAATAGAAACAACG (SEQID NO:76) chr3:114295571 TIGIT TIGIT92.65sgRNA_ CCATTTGTAATGCTGACTTG (SEQID NO:77) chr3:114295700 TIGIT TIGIT60.75sgRNA_ CTGGGTCACTTGTGCCGTGG (SEQID NO:78) chr3:114295634 TIGIT TIGIT87.99sgRNA_ GTCAGGGTTCTGGATATCTG (SEQID NO:79) chrl4:22547508 TRAC TRAC98.20sgRNA_ TGGATTTAGAGTCTCTCAGC (SEQID NQ:80) chrl4:22547541 TRAC TRAC88.15sgRNA_ CTGCGGCTGTGGTCCAGCTG(SEQID N0:81) chrl4:22550661 TRAC TRAC94.77sgRNA_ ACAAAACTGTGCTAGACATG (SEQID NO:82) chrl4:22547658 TRAC TRAC87.86sgRNA_ 1 1C1 1CCCCAGCCCAGGTAA (SEQID NO:83) chrl4:22547778 TRAC TRAC89.85sgRNA_ CGTCATGAGCAGATTAAACC (SEQID NO:84) chrl4:22550625 TRAC TRAC95.81sgRNA_ GAGAGCGCCTGCGACCCGAG (SEQID NO:85) chr!9:58544980 TRIM28 TRIM2889.44 WO 2022/093846 PCT/US2021/056689 sgRNA_ CCAGCGGGTGAAGTACACCA (SEQID NO:86) chr!9:58544869 TRIM28 TRIM2894.79sgRNA_ GGAGCGCTTTTCGCCGCCAG (SEQID NO:87) chr!9:58544839 TRIM28 TRIM2891.81 sgRNA_ TGAGGCCTGGACCTTATGCA (SEQID NO:88)chrl0:33134193 chrl0:33130000- 33140000 desert_ (GS88)69.44 sgRNA_ CCTGGTGGAGTGAACCATGA (SEQID NO:89)chrl0:33132917 chrl0:33130000- 33140000 desert_ (GS89)95.25 sgRNA_ CAAGCACTTAGGTTCCCCTG (SEQID NQ:90)chrl0:33134633 chrl0:33130000- 33140000 desert_ (GS90)91.13 sgRNA_ GGTCTCCCTACAATTCAGCG (SEQID N0:91)chrl0:72294568 chrl0:72290000- 72300000 desert_ (GS91)92.02 sgRNA_ CACAGCGCGTGACTGCAATG (SEQID NO:92)chrl0:72298268 chrl0:72290000- 72300000 desert_ (GS92)90.22 sgRNA_ TCTGGGGCACCAATTCTAGG (SEQID NO:93)chrl0:72292786 chrl0:72290000- 72300000 desert_ (GS93)86.35 sgRNA_ GAGCCATGCTTGGCTTACGA (SEQID NO:94)chrll:128342576 chrll:128340000-128350000 desert_ (GS94)91.24 sgRNA_ GTACAAGTACTTATCTCATG (SEQID NO:95)chrll:128343592 chrll:128340000- 128350000 desert_ (GS95)89.02 sgRNA_ GAGATAACAACATAACAACA (SEQID NO:96)chrll:128347170 chrll:128340000- 128350000 desert_ (GS96)96.47 sgRNA_ CATATTCCATAGTCTTTGGG (SEQID NO:97)chrll:65425000 chrll:65425000- 654270(NEAT1) desert_ (GS97)88.54 sgRNA_ CTGCCCCTTAGCAACTTAGG (SEQID NO:98)chrll:65425507 chrll:65425000- 654270(NEAT1) desert_ (GS98)92.76 sgRNA_ TGTTTAAAAATATGTTGACA (SEQID NO:99)chrll:65426264 chrll:65425000- 654270(NEAT1) desert_ (GS99)90.76 sgRNA_ 100CCAGGAATGGAAACTCACGC (SEQID NQ:100)chr!5:92830315 chrl5:92830000- 92840000 desert_ (GS1)87.84 sgRNA_ 101GAGGCCGCTGAATTAACCCG(SEQID NQ:101)chr!5:92831850 chrl5:92830000- 92840000 desert_ (GS1)85.32 WO 2022/093846 PCT/US2021/056689 sgRNA_ 102ATACACGCACACTTGCAGAA (SEQID NO:102)chrl5:92831131 chr!5:92830000- 92840000 desert_ (GS1)99.92 sgRNA_ 103GAGCAGACAGAAACCCAGGG (SEQID NO:103)chrl6:11225670 chrl6:11220000- 11230000 desert_ (GS1)87.92 sgRNA_ 104TGAGTCTCCAAACAGAACAG (SEQID NQ:104)chr!6:11226284 chrl6:11220000- 11230000 desert_ (GS1)88.53 sgRNA_ 105TAATATCACTGACTTCACGG (SEQID NQ:105)chr!6:11225029 chrl6:11220000- 11230000 desert_ (GS1)87.65 sgRNA_ 106TACACACAATGTAAGCAGCA (SEQID NQ:106)chr2:87467461 chr2:87460000- 87470000 desert_ (GS1)71.79 sgRNA_ 107GGGAGCTCAATTCGAAACCA (SEQID NQ:107)chr2:87468809 chr2:87460000- 87470000 desert_ (GS1)65.89 sgRNA_ 108TTGGACAGGTGAGACAGTCG (SEQID NQ:108)chr2:87467001 chr2:87460000- 87470000 desert_ (GS1)72.64 sgRNA_ 109AAGCTCACTCAGATAGTGTG (SEQID NQ:109)chr3:186511316 chr3:186510000- 186520000 desert_ (GS1)76.89 sgRNA_ 110CAGGAGAACCACCTTACACG(SEQID NQ:110)chr3:186515260 chr3:186510000- 186520000 desert_ (GS110)86.31 sgRNA_ 111GGACAGACCCTGATTCACAA(SEQID NO:111)chr3:186519655 chr3:186510000- 186520000 desert_ (GS111)85.47 sgRNA_ 112ACATGGCAGTCTATGAACAG(SEQID N0:112)chr3:59451154 chr3:59450000- 59460000 desert_ (GS112)87.77 sgRNA_ 113CCTATAGAGAGTACTACTTG(SEQID N0:113)chr3:59456416 chr3:59450000- 59460000 desert_ (GS113)79.33 sgRNA_ 114CCAACCGGGTCTTCATTACG(SEQID N0:114)chr3:59457029 chr3:59450000- 59460000 desert_ (GS114)92.21 WO 2022/093846 PCT/US2021/056689 sgRNA_ 115TCAAGCGTAGAGTTCCGAGT(SEQID NO:115)chr8:127993006 chr8:127980000- 128000000 desert_ (GS115)93.07 sgRNA_ 116TCATGCAATTATGGACCCAG(SEQID NO:116)chr8:127994663 chr8:127980000- 128000000 desert_ (GS116)89.40 sgRNA_ 117CGGGAAAGTGACTGGCCATG(SEQID NO:117)chr8:127996766 chr8:127980000- 128000000 desert_ (GS117)87.45 sgRNA_ 118TGAGATTGAAATCAAATCGG(SEQID NO:118)chr9:7974159chr9:7970000-7980000 desert_ (GS118)84.84 sgRNA_ 119TATGCAATATTCATCACGCG(SEQID NO:119)chr9:7977914chr9:7970000-7980000 desert_ (GS119)85.44 sgRNA_ 120AATGTGTTAAATCAAATGCA (SEQID NQ:120)chr9:7976895chr9:7970000-7980000 desert_ (GS1)83.48 TABLE 5:CONSTRUCTS USED FOR EVALUATION OF PREDICTED LOCI Construct name Sequence Length pARBI- 903: APRT_1_E ndogeno us_l ATCTCGGCCAATAAAGGAGAAAGGGCGCGGCCCGTACGCGCGCCAGGTGCGTGGGCGAG ACCAGCTCACGCCCCTCCTCCAGCCGCCAAGGCCCCGGCCCACAGCTGCCTGGCTGCAGTC AGAAGCGTAGCCCGAGACAAGGAAGGGCGCCTTGACTCGCACTTTTGTCCGGTTCGAACGT TCTGctcagtggtgcgtggaatgcgagcgcgtcttaaaatcgatggcgcctaggagtccatgaaatacggTACAGG CTTCCGGCGACGGATGCCCCGCCCCTCACCCACGCTCCGCCCTCCGGGGATGCCCCACCCCT CGTGGCGGTCCCGCCCGTCCCCGCGCAGGCGCGCTCGGGCTGCCGCTGGCTCTTCGCACGC GGCCATGGCCGACTCCGAGCTGCAGCTGGTTGAGCAGCGGATCCGCAGCTTCCCCGACTTC CCCACCCCAtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggccccA TGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACG GCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACG GCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTC GTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGC ACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAG GACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAAC CGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTG GAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCA AGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTA CCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGC ACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAG TTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagctt ataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtc caaactcatcaatgtatcttatGGCGTGGTATTCAGGTGCACGCACAGGCCGCCCTCGTGGCGCCC CGACCTGCGGGCCTACGGATGGGAGCGCGTGGCCCGCGACCTCCGGGCGGGCGGGGCGG GAACCCTCGTCTTTCGCCCCCGGGGCCCTGCCCTCCTTCGGCCCCGGCGTCACCAGGCCTGT 1806 WO 2022/093846 PCT/US2021/056689 CCTTGGGTCCAGGGACATCTCGCCCGTCCTGAAGGACCCCGCCTCCTTCCGCGCCGCCATCG GCCTCCTGGCGCGACACCTGAAGGCGACCCACGGGGGCCGCATCGACTACATCGCAGGCG AGTGCCCAGTGGCCGCATCTAGGGCGCTTCCGCCTCTGCGCGCGCCGAGGGCAGCACGTG GGCTCTGCGCGTCTGCTTGGGGGAGGGCCTTTGGGGTGCTTCAGGGGGCGCCGGGACGG GCGCCGTGCTTGGGTCGCCCGGGAAGGGTTGTGAGATTGAGCCCpARBI- 904: APRT2E ndogeno us_2 TGCCCCGCCCCTCACCCACGCTCCGCCCTCCGGGGATGCCCCACCCCTCGTGGCGGTCCCGC CCGTCCCCGCGCAGGCGCGCTCGGGCTGCCGCTGGCTCTTCGCACGCGGCCATGGCCGACT CCGAGCTGCAGCTGGTTGAGCAGCGGATCCGCAGCTTCCCCGACTTCCCCACCCCAGGCGT GGTATTCAGGTGCACGCACAGGCCGCCCTCGTGGCGCCCCGACCTGCGGGCCTACGGATG GGAGCGCGTGGCCCGCGACCTCCGGGCGGGCGGGGCGGGAACCCTCGTCTTTCGCCCCCG GGGCCCTGCCCTCCTTCGGCCCCGGCGTCACCAGGCCTGTCCTTGGGTCCAGGGACATCTC GCCCGTCCTGAAGGACCCCGCCTCCTTCCGCGCCGCCATCGGCCTCCTGGCGCGACACCTG AAGGCGACCCACGGGGGCCGCATCtccggatccggagagggcaggggatctctccttacttgtggcgacgtg gaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCC TGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAG GGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCG TGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCC GACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGC GCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGG GCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACA TCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAA GCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGT GCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCC GACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGAT CACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGT ACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattttttt cactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGACTACATCGCAGGCGAGTGCCCAGT GGCCGCATCTAGGGCGCTTCCGCCTCTGCGCGCGCCGAGGGCAGCACGTGGGCTCTGCGC GTCTGCTTGGGGGAGGGCCTTTGGGGTGCTTCAGGGGGCGCCGGGACGGGCGCCGTGCTT GGGTCGCCCGGGAAGGGTTGTGAGATTGAGCCCCCGAGGCCGCCGCGCTGTGCAGGCGTC CTTCCCGCAGGTTCCGGGTCCCCAGCCCAGGACAGGCGTGACCGAGTTGCCGGGTCAGTTG GTCTCCCTGGAGTGCCCAAGCTGAATCCACAGGGCCCAGCTGCCTTGCTTCTTGTTCCTTCT GCGAGCTGGTATTGAGCGCCTGCCACGAGCCAGGCCTTCCCTGGTGAAGATCACGGAATG CCCACCCAGGGAAGGGAGGCCTGGAGGCCTCCGGGAGAGCCCAAGAGGTGGCCCAGGGA GA 1806 pARBI- 905: APRT3E ndogeno us_3 CGTTCTGctcagtggtgcgtggaatgcgagcgcgtcttaaaatcgatggcgcctaggagtccatgaaatacggTAC AGGCTTCCGGCGACGGATGCCCCGCCCCTCACCCACGCTCCGCCCTCCGGGGATGCCCCAC CCCTCGTGGCGGTCCCGCCCGTCCCCGCGCAGGCGCGCTCGGGCTGCCGCTGGCTCTTCGC ACGCGGCCATGGCCGACTCCGAGCTGCAGCTGGTTGAGCAGCGGATCCGCAGCTTCCCCG ACTTCCCCACCCCAGGCGTGGTATTCAGGTGCACGCACAGGCCGCCCTCGTGGCGCCCCGA CCTGCGGGCCTACGGATGGGAGCGCGTGGCCCGCGACCTCCGGGCGGGCGGGGCGGGAA CCCTCGTCTTTCGCCCCCGGGGCCCTGCCCTCCTTCGGCCCCGGCGTCACCAGGCCTGTCCTT GGGTCCAGGtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggcccc ATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGAC GGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTAC GGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCC TCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCA GCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCA AGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGA ACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGC TGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCAT CAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCA CTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTG AGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTG GAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgc 1806 WO 2022/093846 PCT/US2021/056689 dgLlldlddlgglldLdddldddgLddldgLdlLdLdddlllLdLdddldddgLdlllllllLdLlgLdllLldgllglggl ttgtccaaactcatcaatgtatcttatGACATCTCGCCCGTCCTGAAGGACCCCGCCTCCTTCCGCGCC GCCATCGGCCTCCTGGCGCGACACCTGAAGGCGACCCACGGGGGCCGCATCGACTACATC GCAGGCGAGTGCCCAGTGGCCGCATCTAGGGCGCTTCCGCCTCTGCGCGCGCCGAGGGCA GCACGTGGGCTCTGCGCGTCTGCTTGGGGGAGGGCCTTTGGGGTGCTTCAGGGGGCGCCG GGACGGGCGCCGTGCTTGGGTCGCCCGGGAAGGGTTGTGAGATTGAGCCCCCGAGGCCG CCGCGCTGTGCAGGCGTCCTTCCCGCAGGTTCCGGGTCCCCAGCCCAGGACAGGCGTGACC GAGTTGCCGGGTCAGTTGGTCTCCCTGGAGTGCCCAAGCTGAATCCACAGGGCCCAGCTGC CTTG CTTCTTGTTCCTTCTG CG AG CTG GTATTG AG CG CCTG CCACG ApARBI- 906: B2M_1_E ndogeno us_4 AGTAATTTGATGGGGGCTATTATGAACTGAGAAATGAACTTTGAAAAGTATCTTGGGGCCA AATCATGTAGACTCTTGAGTGATGTGTTAAGGAATGCTATGAGTGCTGAGAGGGCATCAGA AGTCCTTGAGAGCCTCCAGAGAAAGGCTCTTAAAAATGCAGCGCAATCTCCAGTGACAGAA GATACTGCTAGAAATCTGCTAGAAAAAAAACAAAAAAGGCATGTATAGAGGAATTATGAG GGAAAGATACCAAGTCACGGTTTATTCTTCAAAATGGAGGTGGCTTGTTGGGAAGGTGGA AGCTCATTTGGCCAGAGTGGAAATGGAATTGGGAGAAATCGATGACCAAATGTAAACACTT GGTGCCTGATATAGCTTGACACCAAGTTAGCCCCAAGTGAAATACCCTGGCAATATTAATGT GTCTTTTCCCGATATTCCTCAGGTtccggatccggagagggcaggggatctctccttacttgtggcgacgtgga ggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCT GGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGG GCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGT GCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCG ACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCG CACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGC GACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATC CTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGC AGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGC AGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGA CAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCAC ATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACA Aatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcact gcattctagttgtggtttgtccaaactcatcaatgtatcttatACTCCAAAGATTCAGGTTTACTCACGTCATC CAGCAGAGAATGGAAAGTCAAATTTCCTGAATTGCTATGTGTCTGGGTTTCATCCATCCGAC ATTGAAGTTGACTTACTGAAGAATGGAGAGAGAATTGAAAAAGTGGAGCATTCAGACTTGT CTTTCAGCAAGGACTGGTC1 1 1L1 ATCTCTTGTACTACACTGAATTCACCCCCACTGAAAAAG ATGAGTATGCCTGCCGTGTGAACCATGTGACTTTGTCACAGCCCAAGATAGTTAAGTGGGG TAAGTCTTACATTCTTTTGTAAGCTGCTGAAAGTTGTGTATGAGTAGTCATATCATAAAGCT GCTTTGATATAAAAAAGGTCTATGGCCATACTACCCTGAATGAGTCCCATCCCATCTGATAT AAACAATCTGCATATTGGGATTGTCAGGGAATGTTCTTAAAGATCAGA 1806 pARBI- 907: B2M_2_E ndogeno us_5 AAGATCTTAATCTTCTGGGTTTCCGTTTTCTCGAATGAAAAATGCAGGTCCGAGCAGTTAAC TG G CTG G G G CACCATTAG C AAGTCACTTAG CATCTCTG G G G CCAGTCTG CAAAG CG AG G G GGCAGCCTTAATGTGCCTCCAGCCTGAAGTCCTAGAATGAGCGCCCGGTGTCCCAAGCTGG GGCGCGCACCCCAGATCGGAGGGCGCCGATGTACAGACAGCAAACTCACCCAGTCTAGTG CATGCCTTCTTAAACATCACGAGACTCTAAGAAAAGGAAACTGAAAACGGGAAAGTCCCTC TCTCTAACCTGGCACTGCGTCGCTGGCTTGGAGACAGGTGACGGTCCCTGCGGGCCTTGTC CTGATTGGCTGGGCACGCGTTTAATATAAGTGGAGGCGTCGCGCTGGCGGGCATTCCTGAA GCTGACAGCATTCGGGCCGAGATGtccggatccggagagggcaggggatctctccttacttgtggcgacgtg gaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCC TGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAG GGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCG TGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCC GACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGC GCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGG GCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACA TCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAA GCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGT 1806 WO 2022/093846 PCT/US2021/056689 GCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCC GACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGAT CACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGT ACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattttttt cactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTCTCGCTCCGTGGCCTTAGCTGTGCTCG CGCTACTCTCTC HILI GGCCTGGAGGCTATCCAGCGTGAGTCTCTCCTACCCTCCCGCTCTG GTCCTTCCTCTCCCG CTCTG CACCCTCTGTG G CCCTCG CTGTG CTCTCTCG CTCCGTG ACTTCC CTTCTCCAAGTTCTCCTTGGTGGCCCGCCGTGGGGCTAGTCCAGGGCTGGATCTCGGGGAA GCGGCGGGGTGGCCTGGGAGTGGGGAAGGGGGTGCGCACCCGGGACGCGCGCTACTTGC CCCTTTCGGCGGGGAGCAGGGGAGACCTTTGGCCTACGGCGACGGGAGGGTCGGGACAA AGTTTAGGGCGTCGATAAGCGTCAGAGCGCCGAGGTTGGGGGAGGGTTTCTCTTCCGCTCT TTCGCGGGGCCTCTGGCTCCCCCAGCGCAGCTGGAGTGGGGGACGGGTAGGCTCGpARBI- 908:B2M_3_E ndogeno us_6 AGGAATGCTATGAGTGCTGAGAGGGCATCAGAAGTCCTTGAGAGCCTCCAGAGAAAGGCT CTTAAAAATGCAGCGCAATCTCCAGTGACAGAAGATACTGCTAGAAATCTGCTAGAAAAAA AACAAAAAAGGCATGTATAGAGGAATTATGAGGGAAAGATACCAAGTCACGGTTTATTCTT CAAAATGGAGGTGGCTTGTTGGGAAGGTGGAAGCTCATTTGGCCAGAGTGGAAATGGAAT TGGGAGAAATCGATGACCAAATGTAAACACTTGGTGCCTGATATAGCTTGACACCAAGTTA GCCCCAAGTGAAATACCCTGGCAATATTAATGTGTCTTTTCCCGATATTCCTCAGGTACTCCA AAGATTCAGGTTTACTCACGTCATCCAGCAGAGAATGGAAAGTCAAATTTCCTGAATTGCTA TGTGTCTGGGTTTCATCCATCCtccggatccggagagggcaggggatctctccttacttgtggcgacgtggagg agaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGG TCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGC GATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGC CCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGAC CACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCA CCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCG ACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCC TGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCA GAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCA GCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGAC AACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACA TGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAA atgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactg cattctagttgtggtttgtccaaactcatcaatgtatcttatGACATTGAAGTTGACTTACTGAAGAATGGA GAGAGAATTGAAAAAGTGGAGCATTCAGACTTGTCTTTCAGCAAGGACTGGTCI 1 ILIATCT CTTGTACTACACTGAATTCACCCCCACTGAAAAAGATGAGTATGCCTGCCGTGTGAACCATG TGACTTTGTCACAGCCCAAGATAGTTAAGTGGGGTAAGTCTTACATTCTTTTGTAAGCTGCT GAAAGTTGTGTATGAGTAGTCATATCATAAAGCTGCTTTGATATAAAAAAGGTCTATGGCC ATACTACCCTGAATGAGTCCCATCCCATCTGATATAAACAATCTGCATATTGGGATTGTCAG GGAATGTTCTTAAAGATCAGATTAGTGGCACCTGCTGAGATACTGATGCACAGCATGGTTT CTGAACCAGTAGTTTCCCTGCAGTTGAGCAGGGAGCAGCAGCAGCACTTG 1806 pARBI- 909: CAPNS1_ lEndoge nous? GATCTCACATTCTAGCGCCCAGACATGTCGGGAACGCCTTACGCCAACTTGGGGTCCCCACC AAGAGAACCCCCACCAGATCTGCACCCTCCCCTTCACGCGTGCACCCAGTCCAGGCTCCCTC AAGCCCCACGGGTGCCTTTTAGACCTGAGGAGGTTGCAAACCTGATCCCCCATACCTGCCCC ACCCATCCGCGGACAACCCGCCCTCGCAAACTCAGACCCCCACCCGGAGGCTTCAGATTCCT CCCAGGTCCAGCTGCCGGAAATGCGTGTTTGAAGGGAGGGTGTGGGCTCAGGGGCGAAG CACCCACTGGTCCCCTTTTTTCCCCCCAGCAGTGAGTCGCAGCCATGTTCCTGGTTAACTCGT TCTTGAAGGGCGGCGGCGGCGGCGGCGGGGGAGGCGGGGGCCTGGGTGGGGGCCTGGG AAATGTGCTTGGAGGCCTGATCtccggatccggagagggcaggggatctctccttacttgtggcgacgtggag gagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTG GTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGG CGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTG CCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGA CCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGC ACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGC 1806 WO 2022/093846 PCT/US2021/056689 GACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATC CTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGC AGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGC AGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGA CAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCAC ATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACA Aatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcact gcattctagttgtggtttgtccaaactcatcaatgtatcttatAGCGGGGCCGGGGGCGGCGGCGGCGGCG GCGGCGGCGGCGGCGGTGGTGGAGGCGGCGGTGGCGGTGGAACGGCCATGCGCATCCTA GGCGGAGTCATCAGCGCCATCAGGTAAGGCGGAGACTATCAGAGGGGCGGGGCCTGGGA ATGGGAGGAGCCTCAGTGAGGCGTGGTCTGGGAGGGGCGTGGTCTAAAAATAGAATAGG ATTAACCTGGAGGCTAACCTGGGTACATGAATTAGGCCGGGGAGGCCTGGTTTGAGAGTT CTGCTGTAAGGGGGTGGACCCCAGTGAGGCGGATATCAGTCATTGGGGGCGGTGCTTGAT ATGGGAGTAGTCTGATTGTGTGGGACCAGGACAATGTGGTCCTGAGGGGACTGATGTGGA GTTTTG G CG G GTG G G G CTTATG G GTCTG G G CTCAG CCTG CATTG G CTAACCTG G AG ATG A A CGTTpARBI- 910: CAPNS1_ 2_Endoge nous_8 CGGGCATTTAGGAAGCGGGCCATGGAGTAGGGTCTTGGGCAGATGGCACCTGAGGAGGA TAAGGCCTTGGGAAGCTGGGGCAGAGCCTCTATGAAGTGAGCCCTCCAAGGGGCGGGGTC TTTTGATTCTACGTGGGATTTTTTAGGTTTAGGGTGGCCAAGATGACTGAAATCTGCCACTG GGTAGGTGTGCCTGGCAGGAGGGGAGCCTCCCAGGGGACCGGTCTCTGGGTTTCCTCGAG GGTGGGGTTGGCCTGAGGAAGGGAGAAGAGGGGCACGACCAGGGCAGTGTGGATTGGG ACAGATGAGGACAAGAACAAATGAAAGGCACAGCAACCAAGTAAGGAAGATAACGGCTG GGGTCTGGAGCGTTGGGGCTGATGGTTCTGTAGTGCTGCCCGTTGGAGGCCCCGCCCCTG GCACTAACCCCTCCCCCTTATCTCTTCGCAGCtccggatccggagagggcaggggatctctccttacttgtg gcgacgtggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTG CCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAG GGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAG CTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCG CTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCC AGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGT TCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACG GCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGC CGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGG CAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTG CTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGC GCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGA GCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagc atttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGAGGCGGCTGCGCAGTACAAC CCGGAGCCCCCGGTAAGCCCCCTCTGCAACCAGACCCCCTTCTCCTGCCAAGGCCTCTTCGA GGTCCCATCCCTGTTCCTGTAGAGAAGCCCCACCTTCCTCCCCTTCTTGTGAAATTCCTCTGC CAGTTCCTCCCATGCCGTGTCTGCAGCTTCGCCATGGGTCTTAGCCATGCCCCACATACGTG CACCCCATTCACTACCACCCCTCATTCTTTTCCTCATCAAGCTGCCCAGCCCACTCTGACTTCC CCACCCAGGGTACCTGGGTTTGGGGAGCCGTCCTGGCCGGGTTCCCCTCCCCCTGCTCTGA GCTCTCCTCCCTTTGCAGCCCCCACGCACACATTACTCCAACATTGAGGCCAACGAGAGTGA GGAGGTCCGGCAGTTCCGGAGACTCTTTGCCCAGCTGGCTGGAGATGTAAGTAAC 1806 pARBI- 911: CAPNS1_ 3_Endoge nous_9 GCTGATGGTTCTGTAGTGCTGCCCGTTGGAGGCCCCGCCCCTGGCACTAACCCCTCCCCCTT ATCTCTTCGCAGCGAGGCGGCTGCGCAGTACAACCCGGAGCCCCCGGTAAGCCCCCTCTGC AACCAGACCCCCTTCTCCTGCCAAGGCCTCTTCGAGGTCCCATCCCTGTTCCTGTAGAGAAG CCCCACCTTCCTCCCCTTCTTGTGAAATTCCTCTGCCAGTTCCTCCCATGCCGTGTCTGCAGCT TCGCCATGGGTCTTAGCCATGCCCCACATACGTGCACCCCATTCACTACCACCCCTCATTCTT TTCCTCATCAAGCTGCCCAGCCCACTCTGACTTCCCCACCCAGGGTACCTGGGTTTGGGGAG CCGTCCTGGCCGGGTTCCCCTCCCCCTGCTCTGAGCTCTCCTCCCTTTGCAGCCCCCACGCAC ACATTACTCCAACtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggc cccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTG GACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCAC 1806 WO 2022/093846 PCT/US2021/056689 CTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCC ACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAA GCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCT TCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGG TGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACA AGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACG GCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCG ACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTA CCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTG CTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgttta ttgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttg tggtttgtccaaactcatcaatgtatcttatATTGAGGCCAACGAGAGTGAGGAGGTCCGGCAGTTCCG GAGACTCTTTGCCCAGCTGGCTGGAGATGTAAGTAACCTGGGGTCCCTGGCCCCGTCCTAA CCGTTCCATCCCTTCCCTTGTGGCTGCCCTTGCACACACACCCTTGACCATGACAATCCCAGT GTTCCCATTCTCCATGACATTCTCAGACCCCTTTCAGTCACCCCTGACCTGCCCCTAACTTCCG CCCGCAGGACATGGAGGTCAGCGCCACAGAACTCATGAACATTCTCAATAAGGTTGTGACA CGACGTAAGTGACCGGGGTTAAGGAATAGGGTAGATTCAGAGGCAGAGGGGTCAGAGAG GATTTGACCTCTGGCCTCTGACTTTCAACCTGTTACCCACAGACCCTGATCTGAAGACTGAT GGTTTTGGCATTGACACATGTCGCAGCATGGTGGCCGTGATGpARBI- 912: CBLB_1_E ndogeno us_10 ggagagttatagcagatggagacaaaaaagggaactgctggggatcaaaccttgtaaagtccttctaagtgatatatga ggactttgacttttattcaaagttagaaggctttgaacaaaagaattatttcatttgtgttttacaatggtcacaagtgccg tagcgagaataggctgTGTAGAGAAGAGATTTTGTGGTTTTCTTTTTTGTTCTCTGTATTCTCTTCC TGAAAAATCTGTTTTCTGCCTAATCATAI 1 ILIGTAAAGAACAATAGACTTGAACGTCTGCTG TTAAGTAACAAAGGTTGACCTAAACCACATAAGGTCAGATTAACTTTTAAAATATCCAAGAT AATGTTAAGTGTATTAAATATGGTTCAGTATGTAATCAAAATATTTGATATTCTCTAGATACT AATCTCttttaatttttttattttttAGCCTTGGtccggatccggagagggcaggggatctctccttacttgtggcgac gtggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCA TCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCG AGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCC CGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACC CCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGA GCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAG GGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAAC ATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACA AGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCG TGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCC CGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGA TCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTG TACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattttt ttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGGCTCTATTTTGCGGAATTGGAATTT CTTAGCTGTGACACATCCAGGTTACATGGCAI 1 ILICACATATGATGAAGTTAAAGCACGAC TACAGAAATATAGCACCAAACCCGGAAGGTAAGACI 1 1 1 1AGCAGTAATATTATGTGATATA TCCAAAGATGAAAAATTCTCCATGGTTTGTTCCTAAGTAAGTCAGCAATACCCGCTGATGGC ATGCTTGGGAGGGGGCTAGAAAAGGTAAAAGACCAAAATGGTGCTTCTTAACATAATGTTT TAAATTGATACATTGTGCTTACTCTGAAACTTGGTATTCATAAAGTGAAAGGGGATATGGTC TCCI 1 ILIGTTTTCATGATATCCGTGTTTATGTGCAAAATTGAATGTATATATTTGAATACTTG AATACTGTGCTAAAGAACAAATAAATAGAACAGTCTTATGTTCATTACTTT 1806 pARBI- 913: CBLB_2_E ndogeno us_ll CATATTACTCATTTGTGCAATGAATAAAGGATTTCTATTATTATATGGACCCATCATCTTATG ACTGI 1 1 1 IAGAAAATGAGAATTAAATCTTGATTCATTATTAAATAACCTTGTATACACACAT GAAGAGGTCATGACACATAAGACTTTGACCTAATACCTTTTTTCAGATATGTTTCTATAGCTA TCTTGATAGCCTAGGACTGTTTGAGAGAAAATTAATTTAAAI 1 1 1 1 GTCATATTCTTAGCAAA TGCAAAATAATTGAGTTAAACAGAACCCACTACATTTGTTCTGAAATATGAACAATATTCTC AAATATTTGTCTGGTAGTACAAATACAATTATATTAATTTTATTATTGAATTTTGCTGCTTCAA AGGGAGGTATTTCTTAAATGATACTTGATTCAATTATTTCCCTTTTTTTCCACCTTGCACAGA ACTATCGTAtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggccccA 1806 WO 2022/093846 PCT/US2021/056689 TGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACG GCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACG GCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTC GTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGC ACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAG GACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAAC CGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTG GAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCA AGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTA CCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGC ACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAG TTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagctt ataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtc caaactcatcaatgtatcttatCCATGGAAAGTATTCAGACAGTGCCTTCATGAGGTCCACCAGATT AGCTCTGGCCTGGAAGCAATGGCTCTAAAATCAACAATTGATTTAACTTGCAATGATTACAT TTCAGI 1 1 1 IGAAI 1IGAIAI 1 1 1 1ACCAGGCTGTTTCAGGTAAGTTTATACTTGCTTAGTCTA TCCATTCCCTtcttctctctccctgtcttttctctctgtttctctctctctctgtctctctctcacacacacacacaTAAAC AAACATATGGAAAATAGTGTCATTCCTATTAGTCTGTAATTTTATTGGTATGTTTGGTCATTG TTAAAAGTTTAGAGTGAGCCATTTGGCTTAAGTTTGGAGTTATCAGATGCTGTGAGCCTGGT GGCTGCTTGTTAGCTTTGAGAGGATCCATCCAAAAGAGCTTTGTTTTAAACTCTCTACTTAGT TTCTTACTTpARBI- 914: CBLB_3_E ndogeno us_12 TTAAACTTTAGAGGTTCAAAATAAGGATATGATATAGAAAAGATTGAATGGTAGGAGAACA GAATAGGATTTATTTATATTATGACAAACGTGACTATCAGTTAATAAATTGGAGATAGTAAG TTAAGATCATTATTTATATTATGGAAAAATGAAGAAATAGGACATGGTTCTCTAACI 1 1 1 IAA Illi ICIGIGAAAIAAAAIAI 1A1 GAG 1 IAIIIIAIIIIIAICIIIGIIII 1AGGTAAGACTGT GCCAAAATCCCAAACTTCAGTTGAAAAATAGCCCACCATATATACTTGATATTTTGCCTGATA CATATCAGCATTTACGACTTATATTGAGTAAATATGATGACAACCAGAAACTTGCCCAACTC AGTGAGAATGAGTACTTTAAAATCTACATTGATAGCCTTATGAAAAAGTCAAAACGGGCAA TAAGACTCTTTAAAtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccg gccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCT GGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCA CCTACG G CAAG CTG ACCCTG AAGTTCATCTG C ACCACCG G CA AG CTG CCCGTG CCCTG G CC CACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGA AGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTT CTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCT GGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCA CAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAAC GGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCC GACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACT ACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCT GCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgttt attgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagtt gtggtttgtccaaactcatcaatgtatcttatGAAGGCAAGGAGAGAATGTATGAAGAACAGTCACAG GACAGGTAAGAAGAATATTTCAGATGTTTTGGTGTAAAGGTCATTTATGTTGCI 1 1 1 IACTT AATAGTTAACCTAAACGTCACCATGTAATTGTTTTGGGGTAAATGTGAGTCGCTTTGTATAT agtcatgtggtacttaacgatggggatactttacaagaaatgcatttttagacaatttcattgttgtgtggacatgataga gtgtacttacacagagctagatggtattacctaccgcacacctaggctgtatgatgtagcctattgctcctaggctgcaaa tctatacagtatgttactgtactgaatactgtgggcagttgtaacacaatggtaagtatgtgtgtatctaaatatacctaaa catagaaaaggtatggtaaaaatactgtataaaaggccgggcgtgg 1806 pARBI- 915: CD2_1_E ndogeno us_13__15 AGATGAGAAAACCTATCCTTCCCAAI Hill 1G 1 GTGAGAATTAAAATGCAGCAAGAAAACA CACACTCATAAACACATCTGCTTTGGCAAAGGAGCACATCAGAAGGGCTGGCTTGTGCGCG CTCTTGCTCTCTGTGTATGTGTATTATGTTTTATGTTACTGTAAAAGATGTAAAGAGAGGCA CGTGGTTAAGCTCTCGGGGTGTGGACTCCACCAGTCTCACTTCAGTTCCTTTTGCATGAAGA GCTCAGAATCAAAAGAGGAAACCAACCCCTAAGATGAGCTTTCCATGTAAATTTGTAGCCA GCTTCCTTCTGATTTTCAATGTTTCTTCCAAAGGTAAGCATAAGAGTCAAAGAAGTCCCAAC 1806 WO 2022/093846 PCT/US2021/056689 CCAGCTTTCCCTGAAAGTGACTCTCAGTAACTCTI 1 IGCI 1 1 1 1ATAGGTGCAGTCTCCAAAG AGATTACGAATGCCTTGtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaac cccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGA GCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATG CCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTG GCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACA TGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCAT CTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACAC CCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGG GCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAG AACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTC GCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACC ACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGT CCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgat tgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattc tagttgtggtttgtccaaactcatcaatgtatcttatGAAACCTGGGGTGCCTTGGGTCAGGACATCAACT TGGACATTCCTAGTTTTCAAATGAGTGATGATATTGACGATATAAAATGGGAAAAAACTTCA GACAAGAAAAAGATTGCACAATTCAGAAAAGAGAAAGAGACTTTCAAGGAAAAAGATACA TATAAGCTATTTAAAAATGGAACTCTGAAAATTAAGCATCTGAAGACCGATGATCAGGATA TCTACAAGGTATCAATATATGATACAAAAGGAAAAAATGTGTTGGAAAAAATATTTGATTT GAAGATTCAAGGTAAGTGTTCATTCCCTTAATTGCTTTATTTCAGTGTGGGTGCTATTTGGC AAGTTGGAAAATAGCAI 1 ILIAATATTCCCCAGCGCTGACCTCTGCCTCCAGGGGGGCTATA CAGGAAACCAGATGCATGTCTCCTGCCCCAGTGGAGACTGTGGTCCAApARBI- 916: CD3E_1_ Endogeno us_16 AGGATTGTTCTAGTTGATTGGTATGTGTGCACTCCTAGTTGTTAAATATTTTCACTATCACAC CTGGATATACTCAACAAATATTTGTTGAGCCAAATACTCAACACCAGCCAAACACGTAGTAT TTACTTTAGCTTAAGCGAATTATTTAGCCCTGACAGAAGCCCTGGAATGTGGGTCTTTAAGT TCCTAI 1 1 1 IGAGATGGGAAAGCTGAGGCTCACGGAAGGAGGTGACCAGCTCAAGTCTCCT ACCGTCCATGCCAAATTAGAATTCCAGCCTGCCTCCTGACTTCAAGTCCAAAGTTCTTCCCAC GCACTAAAGCTAGCTCTTCAGTGTCCTTTCTTAGGAGGTACTTCCTCCCGCACCACTGACCG CCCCCTCTCTATTTCACCCCCAGCCCATCCGGAAAGGCCAGCGGGACCTGTATTCTGGCCTG AATCAGAGACGCATCtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccc cggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAG CTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGC CACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGG CCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACAT GAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATC TTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACC CTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGG CACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGA ACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCG CCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCA CTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTC CTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattg tttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattcta gttgtggtttgtccaaactcatcaatgtatcttatTGACCCTCTGGAGAACACTGCCTCCCGCTGGCCCAG GTCTCCTCTCCAGTCCCCCTGCGACTCCCTGTTTCCTGGGCTAGTCTTGGACCCCACGAGAG AGAATCGTTCCTCAGCCTCATGGTGAACTCGCGCCCTCCAGCCTGATCCCCCGCTCCCTCCTC CCTGCCTTCTCTGCTGGTACCCAGTCCTAAAATATTGCTGCTTCCTCTTCCTTTGAAGCATCAT CAGTAGTCACACCCTCACAGCTGGCCTGCCCTCTTGCCAGGATATTTATTTGTGCTATTCACT CCCTTCCCTTTGGATGTAACTTCTCCGTTCAGTTCCCTCCTTTTCTTGCATGTAAGTTGTCCCC CATCCCAAAGTATTCCATCTACTTTTCTATCGCCGTCCCCTTTTGCAGCCCTCTCTGGGGATG GACTGGGTAAATGTTGACAGAGGCCCTGCCCCGTT 1806 pARBI- 917: CD3E_2_ AATAATAAAATAATAACAATACTTAACATTTATTGAGTGCTTATTAAGTCTCAAGCACTGTCT GTACCCAACACTTATCAAGGATTCI 1 1 1 1 CATGTAATCCTCTCAACAACTATATGGGTTAAGT ATCATTTTATTCCCATGAGTAAAGGGATGAGGAAACAGAGGGTTTGTGAGTTGAAAACACA 1806 WO 2022/093846 PCT/US2021/056689 Endogeno us_17_18TTTCACGCTTCTCACAGCTAGTGAGTAATAAAGCTGGGACTCAAACCCAGGGCTGTTTGACT CCAGTGCCTCTACCCACGGCCACCACTCTTTGCTTGTCAATGTTGTTCTAAACATATTGAAGG GGGGGCTCTGACCGTGGCAAGCGTGTGAGTAGTAAGGGGAGAATGGCCTTCATGCACTCC CTCCTCACCTCCAGCGCCTTGTGTTTTCCTTGCTTAGTGATTTCCCCTCTCCCCACCCCACCCC CCACAGTGTGTGAGtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccg gccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCT GGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCA CCTACG G CAAG CTG ACCCTG AAGTTCATCTG C ACCACCG G CA AG CTG CCCGTG CCCTG G CC CACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGA AGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTT CTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCT GGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCA CAAG CTG G AGTACAACTACAACAG CCACAACGTCTATATCATG GCCG ACAAGCAG AAG AAC GGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCC GACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACT ACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCT GCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgttt attgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagtt gtggtttgtccaaactcatcaatgtatcttatAACTGCATGGAGATGGATGTGATGTCGGTGGCCACAA TTGTCATAGTG G ACATCTG CATCACTG G G G G CTTG CTG CTG CTG GTTTACTACTG G AG CAA GAATAGAAAGGCCAAGGCCAAGCCTGTGACACGAGGAGCGGGTGCTGGCGGCAGGCAAA GGGGTAAGGCTGTGGAGTCCAGTCAGAGGAGATTCCTGCCAAGGGGGACGACCAGCCTG GGCCAGGGTGGGTGGCAAGTCCACAGCTAGGTCAGAACAGCTTCTCTAGAGCTTCTATGCA CAGCTTCTATTACTGTGATGACAAGATCTCAACAGACGGTTTCAAATCTCACATCACTCCCCT CCTTCCCATCCTAGAAAAGTGCAAAAAAGTTTATGAAAGTGATGGGCTTCCTCACATACCTG TCAATGCCTGCAGTCATCCGATTCCGCCCCTAAGCTGTGGGAAGAGAGpARBI- 918: CD3G_1_ Endogeno us_19_20 ACTGTGACCCATGAACCAGTAGGTATTGGCGTCACCTGGGATCCTGACGTTAGTCTCTGTCA ATCCTTCTCTTTAGTTCATCTATTCTACCCAAAGTGATCTCATCATCTGGTATGCTGTTAGCAG TTTCTTACCTGTATAGTATCTTCCAAATAACATGCCCCAAAATCCCAAAGTTTTACCCCTACTA ATTACAGCAATGTCTCTTTTATTCTTCACCCCCTGACGCAGATATTGGCGTCACCCGAGAGC ATGTTAGTAATGCAGAATCTCCCCTCCCCAGAACTACTAAATAGCACCTGAAATTTTAACAA GATCCCCATGTGATTCATGTGCACATCAAAGTTTGAGAAACACTACTCTAATGATCTCCTGG TATGCAGAAGCAGGGAGAATTTCAGAGGCAAGATCCTTAATAGAACCACGGCTTTTCTCAT TTCAGGAAACCACtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccgg ccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTG GACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCAC CTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCC ACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAA GCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCT TCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGG TGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACA AGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACG GCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCG ACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTA CCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTG CTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgttta ttgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttg tggtttgtccaaactcatcaatgtatcttatTTGGTTAAGGTGTATGACTATCAAGAAGATGGTTCGGTA CTTCTGACTTGTGATGCAGAAGCCAAAAATATCACATGGTTTAAAGATGGGAAGATGATCG GCTTCCTAACTGAAGATaaaaaaaaaTGGAATCTGGGAAGTAATGCCAAGGACCCTCGAGGG ATGTATCAGTGTAAAGGATCACAGAACAAGTCAAAACCACTCCAAGTGTATTACAGAAGTA TGTAATCCCCTTTGGTCTGTTTGTTGTGAAATTAATCAGTATTTGCTGTTCTGGTGAGCTTTT TATCTGGGGTGAAAGTGGAAATAGATCCTCAACAGTAATATTATCGCCTGTTCTCTTAATTT CAGCTTGCCTCTTTTAAAATACTGTAAGATACTTCCCTCACCCTATTGAAAAACTACAGCCAG TCCTGTAAAATTTTGTTTACCTTTGGGTGGGCTCCATGG 1806 WO 2022/093846 PCT/US2021/056689 pARBI- 919: CD3G_3_ Endogeno us_21 TTCGAGACAAGCCTGGCCAACATGATGAAACTCTGTCTCTACTAAAAATACAAAAAAAATTA ACCAGGCGTGGAGGCGCGCGCCTGTAGTCCCAGCTACTCAGGAGGCTGAGGCAGGAGGA CCACTTGAACCCAGGAGGTCGAGGTTGCAGTGAGCTGCGATTGTGCCACTGCACTCCAGCC TGGGCAACAGAGAAAGACTCCGTCTCAAAAAAAAAAAAGAGAGAGAGAGAAAAAGAAAA AAGACAGAGCCTCCATCTCCTTGTCCTCTTTCCATCCTCAGGACCATGAAGTACCCACTCCAA ATTCTCACATATAAAAAACATTCAATAAACATGCATCAAATTAATTAATAGAGGATGGAAAA AATGACTTATGACTGTGCTGTCCTTTCCAGCCCCTCAAGGATCGAGAAGATGACCAGTACAG CCACCTTCAAGGAAACCAGTTGtccggatccggagagggcaggggatctctccttacttgtggcgacgtggag gagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTG GTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGG CGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTG CCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGA CCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGC ACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGC GACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATC CTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGC AGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGC AGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGA CAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCAC ATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACA Aatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcact gcattctagttgtggtttgtccaaactcatcaatgtatcttatAGGAGGAATTGAACTCAGGACTCAGAGTA GGTGGGTTCTTCAATGCCAATTCTAATAAAGGACCCTTGCATCAACTGCCCTCGCAATTGCT TCTAAGTCTAGCTCCCTTCCCTAAGCGGCTATAAGCATCAGACTCTGGGGATCAGGGATTG GGACGTGGTTTGGGGTACTCTTTTCTAAAAATTCTGGGGCCATACTGATTGTCTTGGCCTAG GTAAATATGAATTTTATGTATCTGTAAATCCTGTCAGAGCAGGGCCTCAAGCCATAGAGATG CTGAATATTAATCTTAACCTACATTTGAAI 1 ILICATTATCTACACTATTAACATTTTGGGCTA ATTAATTATTTGTGATGAGGGGCTAGCCTGTGCATTGTAGGAGTTATGGAAGCATCCCTGG CCTCTCTCCACCAGATGCTGGTAGATTGTCCAGTGTGACAATCAAAAAT 1806 pARBI- 920: CD5_1_E ndogeno us_22 GACCTCAGGTGATCTGCCCGCCTCAGCTTCCCAAAGTGCTGGGATTACAGGCATGAGCCAC CACACCTGGCCTAAAATTAAI 1 1 1 1AAAGATCTCTTAAAAAGCAGACACCAGCCCCAATCTC AGACCCCTTGAGACAGAATTTCCAGGACAGGGGCCATCCTGCTGGACAGTGGGTGCCGAG AACACCTTGCCCATTTATCTGAGCTCCCTTCTGACTCTGAAATCTGGAGCCCCACCCTCCTGG GTCTAGCTTCGGGGCTGCCTGGGTCAGGGTCCTCTGGGAAGCCCCTGCAGTGCCCCAGAAG GGACGAAGCTCACAAGGGGCAAGGCAGGCAGCCCACGGGGCAGGAGGGAGCTCAACTGG GCGTCCTAGGGAGAGGGCAGTGAGGGGTGCCAGTGGGGAACCCCTCCCAGCCTGACCCCC ACCACACCTTTCTGACCCCCAGATtccggatccggagagggcaggggatctctccttacttgtggcgacgtgg aggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCC TGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAG GGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCG TGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCC GACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGC GCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGG GCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACA TCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAA GCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGT GCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCC GACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGAT CACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGT ACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattttttt cactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTTCCAGGCAAGGCTCACCCGTTCCAAC TCGAAGTGCCAGGGCCAGCTGGAGGTCTACCTCAAGGACGGATGGCACATGGTTTGCAGC CAGAGCTGGGGCCGGAGCTCCAAGCAGTGGGAGGACCCCAGTCAAGCGTCAAAAGTCTGC GAG CG G CTG AACTGTG G G GTG CCCTTAAG CCTTG G CCCCTTCCTTGTCACCTACACACCTCA GAGCTCAATCATCTGCTACGGACAACTGGGCTCCTTCTCCAACTGCAGCCACAGCAGAAAT 1806 WO 2022/093846 PCT/US2021/056689 GACATGTGTCACTCTCTG G G CCTG ACCTG CTTAG GTG G GTAACTAG CCAG CC ACACG G G CA CCCTGGGCCTGGGCGCCAGCCCCGAGGAGACTGCCCGAGGCCTGTGATCTAGGGTCTGAG CAGGCTGGTGGAAGGGGTGGGGGGACCCCAGTTTATAACCACTCCCCAAGACACATACCpARBI- 921: CD52E ndogeno us_23 GGACAGGGGCCATCCTGCTGGACAGTGGGTGCCGAGAACACCTTGCCCATTTATCTGAGCT CCCTTCTGACTCTGAAATCTGGAGCCCCACCCTCCTGGGTCTAGCTTCGGGGCTGCCTGGGT CAGGGTCCTCTGGGAAGCCCCTGCAGTGCCCCAGAAGGGACGAAGCTCACAAGGGGCAAG GCAGGCAGCCCACGGGGCAGGAGGGAGCTCAACTGGGCGTCCTAGGGAGAGGGCAGTGA GGGGTGCCAGTGGGGAACCCCTCCCAGCCTGACCCCCACCACACC HILI GACCCCCAGATT TCCAGGCAAGGCTCACCCGTTCCAACTCGAAGTGCCAGGGCCAGCTGGAGGTCTACCTCAA GGACGGATGGCACATGGTTTGCAGCCAGAGCTGGGGCCGGAGCTCCAAGCAGTGGGAGG ACCCCAGTCAAGCGTCAAAAGTCTGCtccggatccggagagggcaggggatctctccttacttgtggcgacg tggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCAT CCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGA GGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCC GTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCC CGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAG CGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGG GCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACA TCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAA GCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGT GCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCC GACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGAT CACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGT ACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattttttt cactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCAGCGGCTGAACTGTGGGGTGCCCTTA AGCCTTGGCCCCTTCCTTGTCACCTACACACCTCAGAGCTCAATCATCTGCTACGGACAACT GGGCTCCTTCTCCAACTGCAGCCACAGCAGAAATGACATGTGTCACTCTCTGGGCCTGACCT GCTTAGGTGGGTAACTAGCCAGCCACACGGGCACCCTGGGCCTGGGCGCCAGCCCCGAGG AGACTGCCCGAGGCCTGTGATCTAGGGTCTGAGCAGGCTGGTGGAAGGGGTGGGGGGAC CCCAGTTTATAACCACTCCCCAAGACACATACCCAGGAGGGGGACTGGAAGGGGCCAGCA CCCATCTGTAGGATGGCAATGGAGGACCTAGTTCTGCCAATCACTGACTTCATCGTCGCCTC TGAACCTCCATTCTCCCATCTGTGAAGTGGGGTGGTACTTCCCGCCTCGCAGGAGGCT 1806 pARBI- 922: CD53E ndogeno us_24 tgctgggattacaggcatgagccaccacacctggcctaaaattaatttttaaagaTCTCTTAAAAAGCAGACAC CAGCCCCAATCTCAGACCCCTTGAGACAGAATTTCCAGGACAGGGGCCATCCTGCTGGACA GTGGGTGCCGAGAACACCTTGCCCATTTATCTGAGCTCCCTTCTGACTCTGAAATCTGGAGC CCCACCCTCCTGGGTCTAGCTTCGGGGCTGCCTGGGTCAGGGTCCTCTGGGAAGCCCCTGC AGTGCCCCAGAAGGGACGAAGCTCACAAGGGGCAAGGCAGGCAGCCCACGGGGCAGGAG GGAGCTCAACTGGGCGTCCTAGGGAGAGGGCAGTGAGGGGTGCCAGTGGGGAACCCCTC CCAGCCTGACCCCCACCACACCTTTCTGACCCCCAGATTTCCAGGCAAGGCTCACCCGTTCC AACTCGAAGTGCtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggc cccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTG GACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCAC CTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCC ACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAA GCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCT TCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGG TGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACA AGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACG GCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCG ACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTA CCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTG CTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgttta ttgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttg tggtttgtccaaactcatcaatgtatcttatCAGGGCCAGCTGGAGGTCTACCTCAAGGACGGATGGCA CATGGTTTGCAGCCAGAGCTGGGGCCGGAGCTCCAAGCAGTGGGAGGACCCCAGTCAAGC 1806 WO 2022/093846 PCT/US2021/056689 GTCAAAAGTCTG CCAG CG G CTG AACTGTG G G GTG CCCTTAAG CCTTG G CCCCTTCCTTGTCA CCTACACACCTCAGAGCTCAATCATCTGCTACGGACAACTGGGCTCCTTCTCCAACTGCAGC CACAGCAGAAATGACATGTGTCACTCTCTGGGCCTGACCTGCTTAGGTGGGTAACTAGCCA GCCACACGGGCACCCTGGGCCTGGGCGCCAGCCCCGAGGAGACTGCCCGAGGCCTGTGAT CTAGGGTCTGAGCAGGCTGGTGGAAGGGGTGGGGGGACCCCAGTTTATAACCACTCCCCA AGACACATACCCAGGAGGGGGACTGGAAGGGGCCAGCACCCATCTGTpARBI- 923: EDF1_1_E ndogeno us_25 GGGGGCGGCCGCACGGCTAGAGCGGAGACCCCGCGCCCCCTCCGCCCGCGTGGCCCGGCC GGGGTGCGGGGCCCGGGGAGGCACGGGGGCTGCGCGTCGGGGCGCAGCCGCCGCCCGC GTGTGCTCGGAGGCCGCGGGGCCCGGGCTCCGGGGTCCTCCCGACCTGCAGCCCCAGCGG CTACCGCGCCTCGCCAGGCCAGGCCAGGCCCCGACGTCGCCTTCCCTACGTCGCCGGCGCC CGGCCACGACGTCCCTCAGACGAGCCGAACGCCGAATGGCCCCGAGCACGGGAAGTGCCC GCCCCCCGCGTGCAGCCAGCCAATGGGACGCCGAAAGCGGGGAGGTGCCGAGGGGACGT AGCGTCGCCGCGCCAGGTCTCTAGCAGCTGCCGCTGAGCCGCCGGACGGACGCTCGTCTTC GCCCGCCATGGCCGAGAGCGACTGGGACACGtccggatccggagagggcaggggatctctccttacttgt ggcgacgtggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGT GCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGA GGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAA GCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCC GCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGT CCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAA GTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATG GCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGAC GGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGC TGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAA GCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGAC GAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGTGACGGTGCTGCGCAAGA AGGGCCCTACGGCCGCCCAGGCCAAATCCAAGCAGGTGCTTTGCTGACTGAGGAGCGGCC GGGCCGGGCGGGGCGGACGCTgggccggggccacggaccgtggggcagggggctcggggaagggcaggc ggggcctgggacagggcgcaggggacggggacaaggctggGGTGCCGGGGGCAGGACGGGGTTCGAA GGGCGGGGCGAATCGCAGGGGTAGGAGGACCGGGCCAGGACaggggtgggaaggtggggggcg gacccaggaggggatggacggacccaggaggcagggggCGGGCGACTGGAGGAGGAGAGGAGCAGG GAACCGGACGGGGCAAGGGGCAGGCGATAGGGCCGGGACCAGTGCCAGGGTGGGGCGG GGAGGGGATAGGGGCAGGGACTGTTGGTGGGGACAGGTGTGAGGACAG 1806 pARBI- 924:EDF1_2_E ndogeno us_26 ACGGCTAGAGCGGAGACCCCGCGCCCCCTCCGCCCGCGTGGCCCGGCCGGGGTGCGGGGC CCGGGGAGGCACGGGGGCTGCGCGTCGGGGCGCAGCCGCCGCCCGCGTGTGCTCGGAGG CCGCGGGGCCCGGGCTCCGGGGTCCTCCCGACCTGCAGCCCCAGCGGCTACCGCGCCTCGC CAGGCCAGGCCAGGCCCCGACGTCGCCTTCCCTACGTCGCCGGCGCCCGGCCACGACGTCC CTCAGACGAGCCGAACGCCGAATGGCCCCGAGCACGGGAAGTGCCCGCCCCCCGCGTGCA GCCAGCCAATGGGACGCCGAAAGCGGGGAGGTGCCGAGGGGACGTAGCGTCGCCGCGCC AGGTCTCTAGCAGCTGCCGCTGAGCCGCCGGACGGACGCTCGTCTTCGCCCGCCATGGCCG AGAGCGACTGGGACACGGTGACGGTGCTGtccggatccggagagggcaggggatctctccttacttgtgg cgacgtggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGC CCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGG GCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCT GCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCT ACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCA GGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTC GAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGC AACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCG ACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCA GCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCT GCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCG CGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAG 1806 WO 2022/093846 PCT/US2021/056689 CTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagca tttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCGCAAGAAGGGCCCTACGGCCG CCCAGGCCAAATCCAAGCAGGTGCTTTGCTGACTGAGGAGCGGCCGGGCCGGGCGGGGC GGACGCTgggccggggccacggaccgtggggcagggggctcggggaagggcaggcggggcctgggacagggcgc aggggacggggacaaggctggGGTGCCGGGGGCAGGACGGGGTTCGAAGGGCGGGGCGAATCG CAGGGGTAGGAGGACCGGGCCAGGACaggggtgggaaggtggggggcggacccaggaggggatggac ggacccaggaggcagggggCGGGCGACTGGAGGAGGAGAGGAGCAGGGAACCGGACGGGGCA AGGGGCAGGCGATAGGGCCGGGACCAGTGCCAGGGTGGGGCGGGGAGGGGATAGGGG CAGGGACTGTTGGTGGGGACAGGTGTGAGGACAGAGGCAGGAGGTGpARBI- 925: EDF1_3_E ndogeno us_27 CCCTGG AGTCG GTGTG AG GCAAAAG CAG AG G AG AG G ATTTG G AATTAACCTG AAG AAAAA CCATTTCAAAGCGGTAACCAGACCCCAGAGGCTGCCTGAACTCAAGGGGACATGGGAACC CAGGCTGTCCCAAGTTCACACACCTCAGGTCGTGGACTTCCAGAG1 1 1 1L1L1CAGTTATGA GGACAGGCAGCTGTACTCATGCCAACCAGAGCTGCTCTGGGAAGATGGCTGCCTCCCAGG GCTCCGGCCAGCACCGGTGCAGGCAGGCACTCAGCTGACAACGTCCCCGGGGGCGCCGCA CACACCACACCCACCAGCACATGGACCCCACAGCACAGCCTCATGTTGCAAGCGGAAACAC AAGTACCTACATTTCTTGGAAGTCTCCACATCTTCTCCTCGTCTCTGTGCCGCTAAGATAGCC TAGAAAATTAGAAAACATCAGTGGtccggatccggagagggcaggggatctctccttacttgtggcgacgtg gaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCC TGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAG GGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCG TGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCC GACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGC GCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGG GCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACA TCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAA GCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGT GCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCC GACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGAT CACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGT ACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattttttt cactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTIICTAAAGAGAAGATGTGCTTTATAC ACATCAGCTCCACTAGGACTGCTGCAAAACCAGGCGCGAAGCGTCGCCTGAGAACAGCAG CTTCTAGGGCCCCTGGGGTACGCACCCACACGCAGCTGGGTTTTGTGCGAGAGGCAGTGA GAGCCGGGCTGACCTGGCTTCCCGAGGCATTCCCTGCAGGGGAACCAGGGGGGTGGAGCC CACCCTCCCCGTGCTATCTGAACACCGGCCATCCCCCTCCCCAAACCCACAACCCCAGGAGT GAGAGCCCCGGCGCAGCCTCACCGTGGCCAGGTCCTTCTGCGTAAGCCCCTTGCTCTGCCG ACCTTGCTGGATCACCTTGCCCACCTCCAGGGTCACCCTGTCATGGTGCAGCTCCTCTGTCTCCCGGTCCAGCTTGGCCGTGTTCTTGGTAATAGAATGTTGTTTGTTCTGGCCAGCAGC 1806 pARBI- 926: FTL_l_En dogenous 30 CTCTTGCTTCAACAGTGTTTGGACGGAACAGATCCGGGGACTCTCTTCCAGCCTCCGACCGC CCTCCGATTTCCTCTCCGCTTGCAACCTCCGGGACCATCTTCTCGGCCATCTCCTGCTTCTGG GACCTGCCAGCACCG 1 1 1 1 1GTGGTTAGCTCCTTCTTGCCAACCAACCATGAGCTCCCAGATT CGTCAGAATTATTCCACCGACGTGGAGGCAGCCGTCAACAGCCTGGTCAATTTGTACCTGC AGGCCTCCTACACCTACCTCTCTCTGGTGAGTCCCCAGGACGCCCCTGGCCCTAATTTCCTCC AGCTGCGCACCTCCGGCCCTCACTGCACGCGCCAGCCTTCTTTGTGCGGTCGGGTAAACAG AGGGCGGAGTCCCCTTGGCCTCGCCTCCCGCTAACCATTGTTGCCTCCATCTCTTCCCGTAG GGCTTCTATTTCGACtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaacccc ggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGC TGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCC ACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGC CCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATG AAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCT TCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCC TGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGC ACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAA CGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGC 1806 WO 2022/093846 PCT/US2021/056689 CGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCAC TACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCC TGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgt ttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctag ttgtggtttgtccaaactcatcaatgtatcttatCGCGATGATGTGGCTCTGGAAGGCGTGAGCCACTTC TTCCGCGAATTGGCCGAGGAGAAGCGCGAGGGCTACGAGCGTCTCCTGAAGATGCAAAAC CAGCGTGGCGGCCGCGCTCTCTTCCAGGACATCAAGGTAACTAGTGTGTGGGTAATGGACT ACATCTCCCAGCAGGCCGTGCGCGCGAGGAGCCTTGATTTGAGGGCGTAGGTGTCGCGTG GGCTTCTGGGAGATTGAGTTCGGTCTTGTGAGCCCTCTTAACCGCTGGAAATAGAGGCGCA CCTCGTGCAGTGCCCACAACACGCGGCAGTCCACACCGCTGCGTGGTCTTAGGGACGTATA GCTGTAAGAGCTAGGACAGGGTGCGGAGAGTGATAAATACAAGCTGTCACATGTCTTTGT GGCCTGGGCCTCTGACCCCCAACGACTCTTGGGAAATGTAGGTTTAGTTCTpARBI- 927:FTL_2_En dogenous TGGGGCGGGGGGCTGAGACTCCTATGTGCTCCGGATTGGTCAGGCACGGCCTTCGGCCCC GCCTCCTGCCACCGCAGATTGGCCGCTAGCCCTCCCCGAGCGCCCTGCCTCCGAGGGCCGG CGCACCATAAAAGAAGCCGCCCTAGCCACGTCCCCTCGCAGTTCGGCGGTCCCGCGGGTCT GTCTCTTGCTTCAACAGTGTTTGGACGGAACAGATCCGGGGACTCTCTTCCAGCCTCCGACC GCCCTCCGATTTCCTCTCCGCTTGCAACCTCCGGGACCATCTTCTCGGCCATCTCCTGCTTCT GGGACCTGCCAGCACCG1 1 1 1 1GTGGTTAGCTCCTTCTTGCCAACCAACCATGAGCTCCCAG ATTCGTCAGAATTATTCCACCGACGTGGAGGCAGCCGTCAACAGCCTGGTCAATTTGTACCT GCAGGCCTCCTACACCTACtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggaga accccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTC GAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGA TGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCT GGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCAC ATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCA TCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACA CCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGG GGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAA GAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCT CGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAAC CACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATG GTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatg attgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcat tctagttgtggtttgtccaaactcatcaatgtatcttatCTCTCTCTGGTGAGTCCCCAGGACGCCCCTGGC CCTAATTTCCTCCAG CTG CG CACCTCCG G CCCTCACTG CACG CG CCAG CCTTCTTTGTG CG GT CGGGTAAACAGAGGGCGGAGTCCCCTTGGCCTCGCCTCCCGCTAACCATTGTTGCCTCCATC TCTTCCCGTAGGGCTTCTATTTCGACCGCGATGATGTGGCTCTGGAAGGCGTGAGCCACTTC TTCCGCGAATTGGCCGAGGAGAAGCGCGAGGGCTACGAGCGTCTCCTGAAGATGCAAAAC CAGCGTGGCGGCCGCGCTCTCTTCCAGGACATCAAGGTAACTAGTGTGTGGGTAATGGACT ACATCTCCCAGCAGGCCGTGCGCGCGAGGAGCCTTGATTTGAGGGCGTAGGTGTCGCGTG GGCTTCTGGGAGATTGAGTTCGGTCTTGTGAGCCCTCTTAACCGCTGGA 1806 pARBI- 928: PTEN_1_ Endogeno us_31 CTTTGCATAGTTTATCCTATTAGTAATCTATTCTGTCTTTGGAATATGTTTTGTGATGATGAA ATAAATACTATAAATAGTATTATTCCTTTTGCATTGAGAGTCCTGACGAAATGTCCATGTGA CAGTTCATTTTGGGTTTAGCTCTACCTCTAATATGTGACCTATGCTACCAGTCCGTATAGCGT AAATTCCCAGAATATATCCTCCTGAATAAAATGGGGGAAAATAATACCTGGCTTCCTTAATG ATTATATTTAAGACTTATCAAGAGACTATTTTCTATTTAACAATTAGAAAGTTAAGCAATACA TTA1 1 1 1 ICICIGGAAICCAGIGI 1 ICI 1 1 IAAAIACCIGI IAAGI 1 IGIAIGCAACAI 1 ILIA AAGTTACCTACTTGTTAATTAAAAATTCAAGAG IIIIIIIIILIIAIILI GAGG 1 1A1C1 1 1 1 ACCACAGTTtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggccccA TGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACG GCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACG GCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTC GTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGC ACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAG GACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAAC 1806 WO 2022/093846 PCT/US2021/056689 CGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTG GAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCA AGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTA CCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGC ACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAG TTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagctt ataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtc caaactcatcaatgtatcttatGCACAATATCCTTTTGAAGACCATAACCCACCACAGCTAGAACTTA TCAAACCCTTTTGTGAAGATCTTGACCAATGGCTAAGTGAAGATGACAATCATGTTGCAGCA ATTCACTGTAAAGCTGGAAAGGGACGAACTGGTGTAATGATATGTGCATATTTATTACATC GGGGCAAAI 1 1 1 IAAAGGCACAAGAGGCCCIAGAI 1 ILIATGGGGAAGTAAGGACCAGAG ACAAAAAGGTAAGTTAI 1 1 1 1 IGAIGI 1 1 1 1CCTTTCCTCTTCCTGGATCTGAGAATTTATTG GAAAACAGATTTTGGGTTTCTTTTTTTCCTTCAGTTTTATTGAGGTGTAATTGACAAGTAAAA ATTATATATAAATACAATGTATAATATGATGTTTTGATGTATGTGTATATACATTGTGAAATG ATTACTACAGTCAAACTACTTAACATATTCATpARBI- 929: PTEN_2_ Endogeno us_32 GCTACCAGTCCGTATAGCGTAAATTCCCAGAATATATCCTCCTGAATAAAATGGGGGAAAA TAATACCTGGCTTCCTTAATGATTATATTTAAGACTTATCAAGAGACTATTTTCTATTTAACA ATTAGAAAGTTAAGCAATACATTAI 1 1 1 1CTCTGGAATCCAGTGTTTCTTTTAAATACCTGTT AAGTTTGTATGCAACA1 1 ILIAAAGI IACCIACI IGI IAAI IAAAAAI ICAAGAGI 1 1 1 1 1 1 1 CTTATTCTGAGGTTATCI 1 1 1 1ACCACAGTTGCACAATATCCTTTTGAAGACCATAACCCACC ACAGCTAGAACTTATCAAACCCTTTTGTGAAGATCTTGACCAATGGCTAAGTGAAGATGACA ATCATGTTGCAGCAATTCACTGTAAAGCTGGAAAGGGACGAACTGGTGTAATGATATGTGC ATATTTATTACATtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggc cccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTG GACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCAC CTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCC ACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAA GCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCT TCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGG TGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACA AGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACG GCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCG ACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTA CCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTG CTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgttta ttgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttg tggtttgtccaaactcatcaatgtatcttatCGGGGCAAATTTTTAAAGGCACAAGAGGCCCTAGATTTC TATGGGGAAGTAAGGACCAGAGACAAAAAGGTAAGTTAI 1 1 1 1IGAIGI 1 1 1 ICCTTTCCTC TTCCTGGATCTGAGAATTTATTGGAAAACAGATTTTGGGTTTCTTTTTTTCCTTCAGTTTTATT GAGGTGTAATTGACAAGTAAAAATTATATATAAATACAATGTATAATATGATGTTTTGATGT ATGTGTATATACATTGTGAAATGATTACTACAGTCAAACTACTTAACATATTCATCACCTCAC ATAATTATTATTCTCCCCCCAGGGTGAAAGCATTTAAGATCTACAAGCTACAATTTTCAATTA TACAATGTTATTATTAACTATAGTCACTATGCTGTCCAGTAGAGCTTCAGATCTTGTTCATCT TGTGTTCCTCCCTCCCCACCCTCAGTCCCTGGAA 1806 pARBI- 930: PTEN_3_ Endogeno us_33 ATAAATAGTATTATTCCTTTTGCATTGAGAGTCCTGACGAAATGTCCATGTGACAGTTCATTT TGGGTTTAGCTCTACCTCTAATATGTGACCTATGCTACCAGTCCGTATAGCGTAAATTCCCA GAATATATCCTCCTGAATAAAATGGGGGAAAATAATACCTGGCTTCCTTAATGATTATATTT AAGACTTATCAAGAGACTA1 1 1 ILIAI 1 IAACAAI IAGAAAGI IAAGCAAIACAI 1 Al 1 1 1 IC TCTGGAATCCAGTGTTTCTTTTAAATACCTGTTAAGTTTGTATGCAACAI 1 ILIAAAGTTACC TACTTGTTAATTAAAAATTCAAGAG IIIIIIIIILIIAIICIGAGG 1 1A1C1 1 1 1 1ACCACAGT TGCACAATATCCTTTTGAAGACCATAACCCACCACAGCTAGAACTTATCAAACCCTTTTGTGA AGATCTTGACtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggcccc ATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGAC GGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTAC GGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCC 1806 WO 2022/093846 PCT/US2021/056689 TCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCA GCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCA AGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGA ACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGC TGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCAT CAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCA CTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTG AGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTG GAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgc agcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggt ttgtccaaactcatcaatgtatcttatCAATGGCTAAGTGAAGATGACAATCATGTTGCAGCAATTCAC TGTAAAGCTGGAAAGGGACGAACTGGTGTAATGATATGTGCATATTTATTACATCGGGGCA AAI11 1 1AAAGGCACAAGAGGCCCIAGAI 1 ILIATGGGGAAGTAAGGACCAGAGACAAAA AGGTAAGTTAI 1 1 1 1 1 GA 1G 1 1 1 1 1CCTTTCCTCTTCCTGGATCTGAGAATTTATTGGAAAAC AGATTTTGGGTTTCTTTTTTTCCTTCAGTTTTATTGAGGTGTAATTGACAAGTAAAAATTATA TATAAATACAATGTATAATATGATGTTTTGATGTATGTGTATATACATTGTGAAATGATTACT ACAGTCAAACTACTTAACATATTCATCACCTCACATAATTATTATTCTCCCCCCAGGGTGAAA GCATTTAAGATCTACAAGCTACAATTTTCAATTATpARBI- 931: PTPN2_1Endogen ous_34 TAGTGACGGTATCAAGAGCAGCATCCCAGGTTGACTTTCTTTGGGGCAGGACCTTGCTTGT GTCTTAACCCTTGGTTCCTACccaagtttgtctctctagtcctcaactctgaaagccacttgatatcttacacaatt ccttttttgcctgagaaaataaaagtcagttttgatcatttacaaccaaaaatcctaactaacacaGACCTGTTTTTG AAATCAGGTAGATTGGAAGTCTTGGTTTACTTCTTATAAGCCCGTCCGCTGTCTGTCTTGTA ACATCCCAGGAGCAGACTTAACAAGGCCTTCCTGGAGCCTTGCTCTTTCTGTCTGCTTCCCTC ATCTGctctctctcctctctctTCACAGGGTCCACTTCCTAACACATGCTGCCA HILI GGCTTATGG TTTGGCAGCAGAAGACCAAAGCAGTTGTCATGCTGAACCGCtccggatccggagagggcaggggat ctctccttacttgtggcgacgtggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCAC CGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGT GTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCAC CACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAG TGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGA AGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCC GAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTC AAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTC TATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACA TCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACG GCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCC CAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTC GGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaa tttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatATTGTGGAGA AAGAATCGGTGAGTAATATTTAATATTTACAACTTAGTATACTGTATGTGATCATTAGCATA TAAAG ATTTTCATTTTG G G G CC AATATTCATTCCTTAGTTTTG G CCTTTAATTG CTAAAG G CT AGCGGTCAAAGTG 1 1 1 LI G 1CCGGAAAAACICA1G 1A1CCI 1 1 ICCI 1 ICHAAGIAI 1 1 1 IA TAACAATTGCAGACCTTTCATCTCCAAGATAGAAATACAATGGAATAAATATGGACTAGCA GTGACATATAGATCTTTGGAATCCCTAGGAATCCTTATTGACCTATTGTCAATAAGTCCTCTT CCAGCTTTAAGATCTTGTACTGTTCTACTTCAGATTTCTTACTTTATTCTACATTTCATAATTG CTGGI 1 1 1 IAATGATGATGAAAATTTCCTAATCCACTTCTAATTAGATGTGGCAATGACATGC C 1806 pARBI- 932:PTPN22Endogen ous_35 CAGAATTTGAATATGATGTGGCTGACCATAGATACCTCCATTGCATTAATTCTGCTTCATAA AGTGTTTGATGCTTGCTTGTAGGTGTTGAATAGAGCCTAATTAGCAGTAAGTAAACAGATCT agagcacagactttggcatctgaaggaccttggttcaatgctgggactgccacttactagctatgggatctttggtggatt tttaacctttgaaagcctttcatccctcacagatataatggggaagaaaatcgtttccattagtattgtgaggattaaatg attaattgatgtaaacaatgtgctttccatagtacttggcatatcataagtgcttcatGTTATTTTACGCTGGCTGG GAAGATAAGTTTTGCTGTGGAGAATTTAAGAGGGATATTAAAATATAI 1 1 1 1 GTTATTTTAA GGAAATTCGAAATGAGTCCCATGACtccggatccggagagggcaggggatctctccttacttgtggcgacgt ggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATC 1806 WO 2022/093846 PCT/US2021/056689 CTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGA GGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCC GTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCC CGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAG CGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGG GCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACA TCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAA GCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGT GCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCC GACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGAT CACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGT ACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattttttt cactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTATCCTCATAGAGTGGCCAAGTTTCCA GAAAACAGAAATCGAAACAGATACAGAGATGTAAGCCCATGTAAGTACTTGTGGGTTTGTG TGCATGTGTATTTTTTGGTTTGTTTTAGGAGGCAGGATGTAGTGAAAAGGAGGGCTTGGGG TCAGTGTTGATAAATACAGTAATTTTTTTCCTATTTACGTAAGACACGTTCTTTAAGAATTTA AAGGTGTAGAATAGTGGAAGGAAAAATAATTACCCATAATTATTTCATCCTTCAAACATAG GCACCATTATTTTGGTGTATTTCCCACAACCTG Hill CTTATGCACAGTTTTCCTTTCTTTAA AATAATTGTAATTATAGATGTCTATATAATATCCATATGTATTTCCTTTTCATATCATTCCATC CCCTTTGTAAGTTTTGCTTAAAATAGTTATTGGTGTAGTTTGG 1 HillpARBI- 933:PTPN23Endogen ous_36 ACCAGTTATCGTTTTGTAGGTAGACCAATCAATTCTTAGGTACCAAGAATCTGAATGATCCT TTTACTTTTAGGAAGGTAAGTACTTTATTCATTTAACTATGTTTACTCCTGGTCGAI 1 1 1 ICAA GTCACAATGGCTAATGTGCTACAAACAGAAGTGCTTCCTTTCCAGCACTATAGTAATAAACA AGATTGCATTTTATACTCCTTACAAAAAAAGTAGAGAATAGTTTAGGATTTGTCTCAACTCTA TTATGATGCTAATTCA HHICHAIHCHCIGICIHH ATAAATACCTAGAATATTAATATG AAGATAAAAACAGTAATTTTGAAATGACAGTTGTGGTTTATCATTCTCTATTTTCAGATGATC ACAGTCGTGTTAAACTGCAAAATGCTGAGAATGATTATATTAATGCCAGTTTAGTTGACATA GAAGAGGCAtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggcccc ATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGAC GGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTAC GGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCC TCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCA GCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCA AGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGA ACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGC TGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCAT CAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCA CTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTG AGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTG GAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgc agcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggt ttgtccaaactcatcaatgtatcttatCAAAGGAGTTACATCTTAACACAGGCAAGTAATACGATACC ACG CAAATGTCTG AAAATG ATGTGTTTGTGCTTGTTCTG CTTTAAATCATAG GTAAAAGTAT ATCTTGACTTCTTTTGGAAATGAAATGGTATTTCAG 1 Hill 1L1 GACGATGTAATGAATTAT GGACATTATAAGGTTTTGAAGCTTTGAGTATTTAAGATAAAAGGCAAGTTAI 1 1 1 IGATATT ACACGTTCTGTGAAGGAAAATTCTTAGGAAATGGCTTAGGCCAGTTCTTTGGCAGATTGTG TTCCTTACATTATATCTGACACAGAGTGCTGCTTATGCTTCTTAGTGTCTTCTITTCTCTTCCC ATACCCTGTG G CAAA ACCAG AG G CCCTG G ACAG CTCTTCTGTAG CTCCCCCTG CCTCG CATA TATCTTCAG AG AGTACACCAAG CCCTG GATG GTGT 1806 pARBI- 934: PTPN6_1Endogen ous_37 CCTGCTCAAGGGCCGAGGTGTCCACGGTAGCTTCCTGGCTCGGCCCAGTCGCAAGAACCAG GGTGACTTCTCGCTCTCCGTCAGGTAGGTGGGCCCCCCGCAACCCCGGGCATTTTGGCCACT CTCTTGTG CC ATCCAG G CCCTG AACCACTCATTCCTG GTTCCCCGTG G CAGTG CTG ACTCCCC GTCTGTTCCCTTGCCCCCAACCCCCACACTCCCCATCCCTGTCTGTGCCCACCCATGCCCATG TGTGCCCCCACCCAGGACCTCAGCCGATCCCTGCCCTCCTGCCTCTACTCCTGCACCGACTG GCCTCACCGCCTGGTGCCCTGCAGGGTGGGGGATCAGGTGACCCATATTCGGATCCAGAAC 1806 WO 2022/093846 PCT/US2021/056689 TCAGGGGAI 1 ILIAIGACCTGTATGGAGGGGAGAAG 1 1 1GCGACTCTGACAGAGCTGGTG GAGTACTACACTCAGCAGtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaa ccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCG AGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGAT GCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCT GGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCAC ATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCA TCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACA CCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGG GGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAA GAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCT CGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAAC CACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATG GTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatg attgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcat tctagttgtggtttgtccaaactcatcaatgtatcttatCAGGGTGTCCTGCAGGACCGCGACGGCACCAT CATCCACCTCAAGTACCCGCTGAACTGCTCCGATCCCACTAGTGAGAGGTGAGGGCTCCGC ACCCCCGCCATTCCCAAGCAGGGATGAGCCGGCTCCCACCCTGAACAGCCAGGGAGGCAG GGAGACTGGCAGCCGGCGCTGCCTACCCTCCATCCCCTCCCCTCCCTGCACCAGCTGGGGCT CTCAATGTCCCTCCTCCCTGCTGTCCTGGGACCTGGTGTCTCAGAGCCTAACCTACCACCCTT TCCACCTAACCCCGAGGAAGCCACAGAAAGCTGCCTCGCCCTACTCCGGGAGCCCTGGCCG CTGCAACCCAGGTCCCACTGGAGACAGGGAGGCCACTGCTGGTGGCCAGCATGTCGTGCA GGCCAGCTCTGTTGTTAGAAAGCTCTTCTTCCTCTGGAATCGAGCCTGCCTpARBI- 935: PTPN6_2Endogen ous_38 CTGGGTTCGAAGCCCGGTTAGAACTCTGGAGGCTAGGATGGCTTGAACCTGGGAGGTCGA GGCTGCAGAGAGCTGTAACCGCGCCACTGCACTCCAGCCTGGGCAACAGAGCTCTGGAAG CTTGCCCTAGAGTCAGTCAAGGGCCCTAGGCCAGTGAGTAACAGCTCAGCGTCAGTTTCCT CATCTATAAAATGGGGGTAATATCATACCTAGCTCTCAGCATGTTTGTGAGAGACCTAAATG AGGTGGTGGATTTGGAAGCATGTAGCGCAGTGCCTGGCACACAGTAGGTGCTTGATTTCCG GCCCCTCTCTGTGAATGTCTCTGCTCAGCGCCTTCCCCTGTGGCCTGGGTCTTACCTTCCCTG ACGCTGCCTTCTCTAGGTGGTACCATGGCCACATGTCTGGCGGGCAGGCAGAGACGCTGCT GCAGGCCAAGGGCGAGCCCTGGtccggatccggagagggcaggggatctctccttacttgtggcgacgtgga ggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCT GGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGG GCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGT GCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCG ACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCG CACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGC GACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATC CTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGC AGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGC AGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGA CAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCAC ATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACA Aatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcact gcattctagttgtggtttgtccaaactcatcaatgtatcttatACGTTTCTTGTGCGTGAGAGCCTCAGCCAG CCTGGAGACTTCGTGCTTTCTGTGCTCAGTGACCAGCCCAAGGCTGGCCCAGGCTCCCCGCT CAGGGTCACCCACATCAAGGTCATGTGCGAGGTAAGGCAGCCAGGCGGCGGGGGAGCCTC TGCTGAGGCTCCTGTCTGTGACCACAGTGTGGGTGGCAGGGAGGGTCTGCCTGGGCTTGA ATTCAAGGCTGGGGACCCAGGGAGGGAGACTCAAGTCCTGTGAATGGCCTAATTTGGCTC CCCCCAG GGTG G ACG CTACACAGTG GGTG GTTTGG AG ACCTTCG A GAG CCTCACGG ACCTG GTGGAGCATTTCAAGAAGACGGGGATTGAGGAGGCCTCAGGCGCC1 1 IGIUIACCTGCGG CAGGTCAGGGGTGGGCCCAGCTGCCTCCCCACTTCCCCTGAGCTGTCCCCCAGATGT 1806 pARBI- 936:PTPN63 TGTCACATATGTGCAATGCCATGCTCCTGAGCCTTTGATTGCAGACGTGTGGGAAGTGGGC CCCGTCCCCACCCCCAGTGCCACCCTGCTCTGCTTCTCTTCCCTTGCTGTGCTCTAAAACGAG AAGTACAAGTGAGTTCCCCCAAGGGGTCGGCCGCGCCTCTTCCTGTCCCCGCCCTGCCGGC 1806 WO 2022/093846 PCT/US2021/056689 Endogen ous_39TGCCCCAGGCCAGTGGAGTGGCAGCCCCAGAACTGGGACCACCGGGGGTGGTGAGGCGG CCCGGCACTGGGAGCTGCATCTGAGGCTTAGTCCCTGAGCTCTCTGCCTGCCCAGACTAGCT GCACCTCCTCATTCCCTGCGCCCCCTTCCTCTCCGGAAGCCCCCAGGATGGTGAGGTAAGGG CCTGCCACCCACGGTAGACAGGAGGCAAGGGTGCCTGGTGCCCACGGGACCCCTCCTCACT GCCCTGCCTGGGCCGCCCAGGtccggatccggagagggcaggggatctctccttacttgtggcgacgtggagg agaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGG TCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGC GATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGC CCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGAC CACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCA CCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCG ACACCCTG GTG A ACCG C ATCG AG CTG AAG G G CATCG ACTTCAAG G AG G ACG G CAACATCC TGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCA GAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCA GCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGAC AACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACA TGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAA atgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactg cattctagttgtggtttgtccaaactcatcaatgtatcttatTGGTTTCACCGAGACCTCAGTGGGCTGGATG CAGAGACCCTGCTCAAGGGCCGAGGTGTCCACGGTAGCTTCCTGGCTCGGCCCAGTCGCAA GAACCAGGGTGACTTCTCGCTCTCCGTCAGGTAGGTGGGCCCCCCGCAACCCCGGGCATTT TGGCCACTCTCTTGTGCCATCCAGGCCCTGAACCACTCATTCCTGGTTCCCCGTGGCAGTGC TGACTCCCCGTCTGTTCCCTTGCCCCCAACCCCCACACTCCCCATCCCTGTCTGTGCCCACCC ATGCCCATGTGTGCCCCCACCCAGGACCTCAGCCGATCCCTGCCCTCCTGCCTCTACTCCTGC ACCGACTGGCCTCACCGCCTGGTGCCCTGCAGGGTGGGGGATCAGGTGACCCATATTCGG ATCCAGAACTCAGGGGATTTCTATGACCTGTATGGAGGGGAGAAGTTTGpARBI- 937:PTPRC_1_ Endogeno us_40 TCTTTAGCTAATGTTCTGTAGCTTGTTTTAGATCTGTGTCTACATATTATATGTATCTCTGTAT GCATCAATATTTGTATATATGCATGCATATATGTGTATGTATATTTATGAATACATATACACA CCATATACATACACTTATGTATGGTGTGTGCATATGTATGTGTAGATATATGTACATACACA CTATAGTGGACTGGGGAGTTAGTATACTGGGAGGAGCATACATTTAGGGTATGATTCACAT ATTTATTTTGTCCTTCTCCCATTTTCCATTAATTAACAGGATTGACTACAGCAAAGATGCCCA GTGTTCCACTTTCAAGTGACCCCTTACCTACTCACACCACTGCATTCTCACCCGCAAGCACCT TTGAAAGAGAAAATGACTTCTCAGAGACCACAACTTCTCTTAGTCCAGACAATACTTCCACC CAAGTATCCCCGtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggcc ccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGG ACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCT ACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCAC CCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAG CAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTT CAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGT GAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAA GCTGG AGTACAACTACAACAG CCACAACGTCTATATCATG GCCG ACAAG CAG AAG AACG G CATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGAC CACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACC TGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCT GGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattg cagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtg gtttgtccaaactcatcaatgtatcttatGACTCTTTGGATAATGCTAGTGCTTTTAATACCACAGGTTG GCACACAAAAGTTGTTAACTTAAATATCAGGGAATGTCATTTAGAAAATTCTACAGTTATCA GTACAACTTGTCTTTAAATTATTTGCACAG 1 1 ILIAAGTATGTGATTTTATTCAAGTGCAGAA ATTGCAGGAAATTAGTATCTGTGAAATATAGATCGACTGAAGTAATTAATGCATGTTGTTAG GGAGTGGAGAGAGAAAAGAAGGGAAGCAAGATCTCCAAGGACAATCAGGAGGGGAAATT TGTTCTAGTATCCTCTGATCTATACACACTCGCCATGATTCTCCCGCTTGGCTTCCCGCCACCT GGACAGATGAGAATTTCCCTAGTTCAGAGATTATCAGTTCTACTCTCCTTGGAAGGTGTCTT AAATGGGAGTCTTCCCATTTCTTTGTTTCACTCTAGA 1806 WO 2022/093846 PCT/US2021/056689 pARBI- 938:PTPRC_2_ Endogeno us_41 AGGGAAI 1 1 1 1AIATGTTGGTCATATTATATCCCTAGCATGTGGCATAATGTCTAGCACAAA ATAG GTG CTCAATTAATCATC ATTATCTA AATAAATAATG CATTTG G G AAAAAAAAGTTTCA AAAGI 1 1 1 1CAAAAGTCTTTTGCAGGCTTGAAATTAATCCCAATAGTGATCCTTTAGTCTGTT ATGI 1 ILIGATTTAGCCTGGGGATTCAAAAAATAAATAACATAATTTTGATATATTTGGGCTT TGTAAACATGGTACTAAGAGAGGAAATATAGTTTCATTAGGGTAAAAGCTACTGAAAATTG CCACTTGGTGAATGTTCTATCATAGACTTGAGGTACATATAAAAATCTAATATATGTTTACAT TAATATGAATGAAATTTGAAATTTTCTAAGAGAI 1 1 1 1 GTTTCTTCTTTGCAGGGCAAAGCCC AACACCTTCCCCCtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggc cccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTG GACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCAC CTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCC ACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAA GCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCT TCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGG TGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACA AGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACG GCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCG ACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTA CCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTG CTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgttta ttgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttg tggtttgtccaaactcatcaatgtatcttatACTGGTAAGAATTAATATTTATATTTTTACTAATTTTATTT TCTTGTTGCAAAGTTTATATATTTAACTACAATTTTCTATTATTAACACTGAAATTA 1 1 1 1 IAA GGATAAATTTTATAATCATGAGTGATTCTTGACATTCACTTGTTCTTAAACI 1 ILIGCTTATAC GTTATAGAGTTTAATAACTACCTAAACATGTTATTAAATTTGTATATATATTTTGTGTATAAA TAGTAACTTTTCCCAAACTTGACAGTAAATCACACAACAGG 1 1 1L1ACTCTCTTTTAATATTTT AAGACTATAAAAAAATGCATTTAAATTAGATAACAAAATTTTATAGTCTGAAAGCAGGTTAA CAGCTGTCTATGTATGTTATAGATATGTAGATAACAGATTTGCATATGTCTATATTTCTTTAA GAGTATGTTGCI Illi 1CAATGGTATGCA 1806 pARBI- 939:PTPRC_3_ Endogeno us_42 CCTTTAGCACCATAAAGAAACTAAATTA 1 1 IAGATGI 1 1 1 1A1 GAGAACATATCAAAAAGTA CHI 1CTGTCATCCAATACTTCCACAAATAAATCATTAGTTCTTGCTAATCTTCATCTGGCATA AAAATAATGACATCAACTTTCTTCATGTAATTTCCCACTTAATTCCTTTACTAGGAGCAATAT CAATTCCTATATGACGTCATTGCCAGCACCTACCCTGCTCAGAATGGACAAGTAAAGAAAAA CAACCATCAAGAAGATAAAATTGAATTTGATAATGAAGTGGACAAAGTAAAGCAGGATGCT AATTGTGTTAATCCACTTGGTGCCCCAGAAAAGCTCCCTGAAGCAAAGGAACAGGCTGAAG GTTCTGAACCCACGAGTGGCACTGAGGGGCCAGAACATTCTGTCAATGGTCCTGCAAGTCC AGCTTTAAATCAAGGTtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaacc ccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAG CTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGC CACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGG CCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACAT GAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATC TTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACC CTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGG CACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGA ACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCG CCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCA CTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTC CTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattg tttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattcta gttgtggtttgtccaaactcatcaatgtatcttatTCATAGGAAAAGACATAAATGAGGAAACTCCAAAC CTCCTGTTAGCTGTTAI 1 ICIAI 1 1 1 1GTAGAAGTAGGAAGTGAAAATAGGTATACAGTGGA TTAATTAAATGCAGCGAACCAATATTTGTAGAAGGGTTATATTTTACTACTGTGGAAAAATA TTTAAGATAGTTTTGCCAGAACAGTTTGTACAGACGTATGCTTATTTTAAAATTTTATCTCTT ATTCAGTAAAAAACAACTTCTTTGTAATCGTTATGTGTGTATATGTATGTGTGTATGGGTGT 1806 WO 2022/093846 PCT/US2021/056689 GTGTTTGTGTGAGAGACAGAGAAAGAGAGAGAATTCTTTCAAGTGAATCTAAAAGCTTTTG Cl 1 1 1 cell 1G1 1 1 1 1ATGAAGAAAAAATACATTTTATATTAGAAGTGTTAACTTAGCTTGAA GGATCTGI 1 1 1 1AAAAATCATAAACTGTGTGCAGACTCAATApARBI- 940: PTPRCAP _l_Endog enous_43 aaggaaaaaggcactgagtgctggggggtgctggggtgggctgcagtgatagacatcagggtagaggttaaggtcag gttcagcctcactggggtgaagtttgagcacggtgagcaggccatgcagcccgggggaggggaggatgggaggaggt ggagctttccgggcagagggaacagccagtgcgaaggccccaggcaggtggcttaatgcagctgttgggggaggtgag tggtagggaggaggctggagggatgggggctgatctcacagggccagagcctggttgaccaaataaggccttggccttt tctGCTTGGCTGTCCCAAGAGGATCCCAAAGAGAAAAAAACGAAAGTGGTCTTGGTCACCCA GCCTGCCCCACACCAGGCCCCACCCCAGGTGCTGAGCCCTCTGAGCCCCTGCCTGTCTCCCA CAGGCTCTGCCCTGCtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaacccc ggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGC TGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCC ACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGC CCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATG AAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCT TCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCC TGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGC ACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAA CGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGC CGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCAC TACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCC TGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgt ttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctag ttgtggtttgtccaaactcatcaatgtatcttatACCTTAGGGCTCGGGATGCTGCTGGCCCTGCCAGGG GCCTTGGGCTCGGGTGGCAGCGCGGAGGACAGCGTGGGCTCCAGCTCTGTCACCGTTGTCc tgctgctgctgctgctcctactgctgGCCACTGGCCTAGCACTGGCCTGGCGCCGCCTCAGCCGTGAC TCAGGGGGCTACTACCACCCGGCCCGCCTAGGTGCCGCGCTGTGGGGCCGCACGCGGCGC CTGCTCTGGGCCAGCCCCCCAGGTCGCTGGCTGCAGGCCCGAGCTGAGCTGGGGTCCACA GACAATGACCTTGAGCGACAGGAGGATGAGCAGGACACAGACTATGACCACGTCGCGGAT GGTGGCCTGCAGGCTGACCCTGGGGAAGGCGAGCAGCAATGTGGAGAGGCGTCCAGCCC AGAGCAGGTCCCCGTGCGGGCTGAGGAAGCCAGAGACAGTGACACG 1806 pARBI- 941: PTPRCAP_2_Endog enous_44 aaggtcaggttcagcctcactggggtgaagtttgagcacggtgagcaggccatgcagcccgggggaggggaggatggg aggaggtggagctttccgggcagagggaacagccagtgcgaaggccccaggcaggtggcttaatgcagctgttggggg aggtgagtggtagggaggaggctggagggatgggggctgatctcacagggccagagcctggttgaccaaataaggcct tggccttttctGCTTGGCTGTCCCAAGAGGATCCCAAAGAGAAAAAAACGAAAGTGGTCTTGGT CACCCAGCCTGCCCCACACCAGGCCCCACCCCAGGTGCTGAGCCCTCTGAGCCCCTGCCTGT CTCCCACAG G CTCTG CCCTG CACCTTAG G G CTCG G G ATG CTG CTG G CCCTG CCAG G G G CCT TGGGCTCGGGTGGCAGCGCGGAGGACAGCtccggatccggagagggcaggggatctctccttacttgtgg cgacgtggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGC CCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGG GCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCT GCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCT ACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCA GGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTC GAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGC AACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCG ACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCA GCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCT GCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCG CGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAG CTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagca tttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGTGGGCTCCAGCTCTGTCACCGT TGTCctgctgctgctgctgctcctactgctgGCCACTGGCCTAGCACTGGCCTGGCGCCGCCTCAGCC GTGACTCAGGGGGCTACTACCACCCGGCCCGCCTAGGTGCCGCGCTGTGGGGCCGCACGC GGCGCCTGCTCTGGGCCAGCCCCCCAGGTCGCTGGCTGCAGGCCCGAGCTGAGCTGGGGT 1806 WO 2022/093846 PCT/US2021/056689 CCACAGACAATGACCTTGAGCGACAGGAGGATGAGCAGGACACAGACTATGACCACGTCG CGGATGGTGGCCTGCAGGCTGACCCTGGGGAAGGCGAGCAGCAATGTGGAGAGGCGTCC AGCCCAGAGCAGGTCCCCGTGCGGGCTGAGGAAGCCAGAGACAGTGACACGGAGGGCGA CCTGGTCCTCGGCTCCCCAGGACCAGCGAGCGCAGGGGGCAGTGCTGAGGCCCTGCTGAG TpARBI- 942: PTPRCAP_3_Endog enous_45 cagtgcgaaggccccaggcaggtggcttaatgcagctgttgggggaggtgagtggtagggaggaggctggagggatg ggggctgatctcacagggccagagcctggttgaccaaataaggccttggccttttctGCTTGGCTGTCCCAAGAG GATCCCAAAGAGAAAAAAACGAAAGTGGTCTTGGTCACCCAGCCTGCCCCACACCAGGCCC CACCCCAGGTGCTGAGCCCTCTGAGCCCCTGCCTGTCTCCCACAGGCTCTGCCCTGCACCTT AGGGCTCGGGATGCTGCTGGCCCTGCCAGGGGCCTTGGGCTCGGGTGGCAGCGCGGAGG ACAGCGTGGGCTCCAGCTCTGTCACCGTTGTCctgctgctgctgctgctcctactgctgGCCACTGGCC TAGCACTGGCCTGGCGCCGCCTCAGCCGTGACTCAGGGGGCTACTACtccggatccggagagggc aggggatctctccttacttgtggcgacgtggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCT GTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTT CAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCAT CTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGC GTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCAT GCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACC CGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATC GACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCAC AACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCC ACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCG GCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAA AGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGAT CACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatag catcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCAC CCGGCCCGCCTAGGTGCCGCGCTGTGGGGCCGCACGCGGCGCCTGCTCTGGGCCAGCCCC CCAGGTCGCTGGCTGCAGGCCCGAGCTGAGCTGGGGTCCACAGACAATGACCTTGAGCGA CAGGAGGATGAGCAGGACACAGACTATGACCACGTCGCGGATGGTGGCCTGCAGGCTGAC CCTGGGGAAGGCGAGCAGCAATGTGGAGAGGCGTCCAGCCCAGAGCAGGTCCCCGTGCG GGCTGAGGAAGCCAGAGACAGTGACACGGAGGGCGACCTGGTCCTCGGCTCCCCAGGACC AGCGAGCGCAGGGGGCAGTGCTGAGGCCCTGCTGAGTGACCTGCACGCCTTTGCTGGCAG CGCAGCCTGGGATGACAGCGCCAGGGCAGCTGGGGGCCAGGGCCTCCATGTCACCGCACT GTAGAGGCCGGTCTTGGTGTCCCATCCC 1806 pARBI- 943:RPS23_1_ Endogeno us_46 ATAGAGTAGGGCGGGGGATGCCATGGAGAGGCTCCATGGGGGAGGGCCGGGGAAGCGC CGCTCCAGGAGGCACGTGGTCCGGCGCGGAAGGGGCCCATGAGGCGTGGAGGCCGCCGA GGTCGGGGTACCGAGGGACGCAGGGAGGCCAGCGCTTCCTCCCGGGCATTCGAGCGGGG CCTCGTCCTTCGGGAGAACACATTCTCCGGAGCCCTCTTCGAACGTTTATTAGTCGGTTCAG GG CAACTTG AAG G CCAAATGTTTG G CCCAC AG G CCAATAAATAGTACG AG AG CCA ATCG G CTTAAGGGTTTATTCCAGGTGAGGCGAGTGTCTTAGAAGATGGGAAACACGTAGATGGCG TGI 1 1 1 IACGGAAGAACIAAAAIAI1 IAAI 1 1 1 1AGGCAAGTGTCGTGGACTTCGTACTGCT AGGAAGCTCCGTAGTCACCGACGAGACCAGtccggatccggagagggcaggggatctctccttacttgtg gcgacgtggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTG CCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAG GGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAG CTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCG CTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCC AGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGT TCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACG GCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGC CGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGG CAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTG CTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGC GCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGA GCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagc 1806 WO 2022/093846 PCT/US2021/056689 alllllltcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatAAGTGGCATGATAAACAGTATA AG AAAG CTCATTTG G G CACAG CCCTAA AG G CCAACCCTTTTG G AG GTG CTTCTCATG CAAA AGGAATCGTGCTGGAAAAAGTGTAAGTCCATTGCTCCCGTCAAGTTTTAGTTTATTATAGGA ATTCGAGACATGAACTTACGAATTCTTGTTTTGAAAGTAATTGCAGG 1 1 1 1 IGTGTAGTAGT ATTCATTTG G G CATTGTG G G GTAAAATTG CA AAG CGTTTGTTCTATTTAAAAGTTG GTAAAA TTAGI 1 1 1 1 GGGAATTAGGTAGTTAAGGTTTTAATTTAACGTTGGCCTGGAAGGAATTGGA GAAGATACTAGCAATGATGAAGTAAAGGACACAAACACCTTTACTGTGGGAGTTGTTATAA GTAAATGGCACGTGTCAGCTATTGAACTTTATCGACTTGATAAAACTAAGGTGAAGAGApARBI- 944:RPS23_2_ Endogeno us_47_48 CAAGCGGGACTTGGGGTCTTGGGGACGGGCGGGCGGATGCGAATAGAGTAGGGCGGGG GATGCCATGGAGAGGCTCCATGGGGGAGGGCCGGGGAAGCGCCGCTCCAGGAGGCACGT GGTCCGGCGCGGAAGGGGCCCATGAGGCGTGGAGGCCGCCGAGGTCGGGGTACCGAGG GACGCAGGGAGGCCAGCGCTTCCTCCCGGGCATTCGAGCGGGGCCTCGTCCTTCGGGAGA ACACATTCTCCGGAGCCCTCTTCGAACGTTTATTAGTCGGTTCAGGGCAACTTGAAGGCCAA ATGTTTGGCCCACAGGCCAATAAATAGTACGAGAGCCAATCGGCTTAAGGGTTTATTCCAG GTGAGGCGAGTGTCTTAGAAGATGGGAAACACGTAGATGGCGTGI 1 1 1 IACGGAAGAACT AAAATATTTAATTTTTAGGCAAGTGCCGCGGAtccggatccggagagggcaggggatctctccttacttgt ggcgacgtggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGT GCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGA GGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAA GCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCC GCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGT CCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAA GTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATG GCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGAC GGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGC TGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAA GCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGAC GAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCTTCGTACTGCTAGGAAGCT CCGTAGTCACCGACGAGACCAGAAGTGGCATGATAAACAGTATAAGAAAGCTCATTTGGG CACAGCCCTAAAGGCCAACCCTTTTGGAGGTGCTTCTCATGCAAAAGGAATCGTGCTGGAA AAAGTGTAAGTCCATTGCTCCCGTCAAGTTTTAGTTTATTATAGGAATTCGAGACATGAACT TACGAATTCTTGTTTTGAAAGTAATTGCAGG 1 1 1 1 1GTGTAGTAGTATTCATTTGGGCATTGT GGGGTAAAATTGCAAAGCGTTTGTTCTATTTAAAAGTTGGTAAAATTAG 1 1 1 1 IGGGAATTA GGTAGTTAAGGTTTTAATTTAACGTTGGCCTGGAAGGAATTGGAGAAGATACTAGCAATGA TGAAGTAAAGGACACAAACACCTTTACTGTGGGAGTTGTTATAAGTAAATGGCACGTGTCA 1806 pARBI- 945:RTRAF_1_ Endogeno us_49 TTGTATATCCI 1 1 1 IAAAGTTATTCI 1 1 1 IAGI TAATTGCTCTATGTGTATTGAGACTAGGAAT CAGAAAGCTTAGATTCTAGTCCCAGGTGTAAGTTGTGTAACCCTTGGCAAGTGTCAATCTCT AGGCCTCAGCI 1 1 LI CA 1 Cl Al AAAAIGAGGAAG 1 IG ICG IAI ICIAI 1 1 1 1 1 1 ICTTAAGAT GATACACTTAAATGTTCCCTTCTGTTGGGTTATATAATTGCATCAAAAGTGTAGTAATGTTAT TAAAAAATTGTTAGAGATCCAAACTAAGGTCTCTTTCAACTCTCCCATTCI Illi 1 ClGTGACT TTATGGTAATAATGAAACTGGTGGTTTTCTTTTCTTCCCCCTCACAGTATCTCAGAGATGTTA ACTGTCCTTTCAAGATTCAAGATCGACAAGAAGCTATTGACTGGCTTCTTGGTTTAGCTGTT AGACTTGAAtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggccccA TGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACG GCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACG GCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTC GTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGC ACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAG GACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAAC CGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTG GAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCA AGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTA CCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGC 1806 WO 2022/093846 PCT/US2021/056689 ACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAG TTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagctt ataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtc caaactcatcaatgtatcttatTATGGAGATAATGGTACGTTTTGTGGGGAATGTGTATTTTAAAGA GAGAGGAAAGATGGGAAAGGGAGTGTGAAAATGTAGGGAACTTTGCAGTTTGTTTTGTCT AGTACTATTTTACCTTTGGTTTATTCTTATCACAAGTTAAAAGCACTTTTATTGTCTTTCATTG GTGTTTATATAI 1 ILIGTTAGAATTTGGAAATGGTGCCCTCTGGAGAAGGCTAATTGACTGT CTTCTCACAGAGTAACACTACTTTGATAATATGGTCTGCACCTTAGCCTTTCAAATTAAATTG Illi 1 AG 1G 1CCCAGAAI IGAIGGGACI 1 1 GAAG 1 G 1 IGI IGCAGIAGGIAAI 1 ILICAAAA GACTGAAACATGTCTAATGCCAATATACATTAATACTCTATAGGCCAGAATATATTACTTAT GTTTACTGTCTTAG CACAG ATACTTCTATG GTpARBI- 946:RTRAF_2_ Endogeno us_50 GCACCTGTTATGTAGGAGGAGTAATAAAATGAATGAATGCACTCAAAACACTAAACAGTAA TTCTGTAATCCAACGG G AGGTACAG CG AATACCAAAAG CCTACATATACTATTCTCTG CATG CTATAG CA AG AAAG AAAG G A AAGTG G CTTCCCG GTG GTTTTCTG CCTATTGTAC AACCAG G AAGCTGACAATAAAGTTTATTTGAGCGTCGACGTGCGCCGACGTGGCCCCGCCTCCCCAGC CGGAGCCGCGATTGGTGGGCATTTGCCGGCGGCCACCGCTTTTAAGCCACGATTGGCGAA GGCCGCCGTCATTTCGGAGCGACTCAGCGCCTGCCCGCCCTCTCGCCGCGTCGCCGGTGCC TGCGCCTCCCGCTCCACCTCGCTTCTTCTCTCCCGGCCGAGGCCCGGGGGACCAGAGCGAG AAGCGGGGACCATGTTCCGACGCtccggatccggagagggcaggggatctctccttacttgtggcgacgtgg aggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCC TGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAG GGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCG TGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCC GACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGC GCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGG GCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACA TCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAA GCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGT GCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCC GACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGAT CACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGT ACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattttttt cactgcattctagttgtggtttgtccaaactcatcaatgtatcttatAAGTTGACGGCTCTCGACTACCACAAC CCCGCCGGCTTCAACTGCAAAGGTGAGGCGGCGGCCTCAGCCCGGCCGCGTGTCCCTGACC TGGGCGGAGGTCCCAGCCTCAGTGCCCGCACCCCACCTCCCCGTCGGGACCCTCGGCGGCC TGGTTTCCGCCGGCAGCCTCCGGGCCCCTCTCCTCTGGGTCGCCACGTACCTCGGCTCTTCG CCGCCCCTTCCCGCCTTTAAAGCCCTCTCACCTACTCCTGTCTCGGCATGTTACI 1 ILIGCACT TGCTTAACTCCAAGCATCACGTAACTACCTTCTCTGTACATAAAAGGGAGAGCATTCGTCTT TCTCACTCACTATTCAACTCCATGGTTCCCTGGGTAATTAGGCGATACCTTGAGCACCTGCTA ATTATGGGCCAGCGCGGTGCTGGATTCTGAGGAAGGTGCTGAGTAACTTG 1806 pARBI- 947:RTRAF_3_ Endogeno us_51 CACTAAACAGTAATTCTGTAATCCAACGGGAGGTACAGCGAATACCAAAAGCCTACATATA CTATTCTCTGCATGCTATAGCAAGAAAGAAAGGAAAGTGGCTTCCCGGTGGTITICTGCCTA TTGTACAACCAGGAAGCTGACAATAAAGTTTATTTGAGCGTCGACGTGCGCCGACGTGGCC CCGCCTCCCCAGCCGGAGCCGCGATTGGTGGGCATTTGCCGGCGGCCACCGCTTTTAAGCC ACGATTGGCGAAGGCCGCCGTCATTTCGGAGCGACTCAGCGCCTGCCCGCCCTCTCGCCGC GTCGCCGGTGCCTGCGCCTCCCGCTCCACCTCGCTTCTTCTCTCCCGGCCGAGGCCCGGGGG ACCAGAGCGAGAAGCGGGGACCATGTTCCGACGCAAGTTGACGGCTCTCGACTACCACAA CCCCGCCGGCTTCAACTGCAAAtccggatccggagagggcaggggatctctccttacttgtggcgacgtggag gagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTG GTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGG CGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTG CCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGA CCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGC ACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGC GACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATC 1806 WO 2022/093846 PCT/US2021/056689 CTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGC AGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGC AGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGA CAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCAC ATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACA Aatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcact gcattctagttgtggtttgtccaaactcatcaatgtatcttatGGTGAGGCGGCGGCCTCAGCCCGGCCGCG TGTCCCTGACCTGGGCGGAGGTCCCAGCCTCAGTGCCCGCACCCCACCTCCCCGTCGGGAC CCTCGGCGGCCTGGTTTCCGCCGGCAGCCTCCGGGCCCCTCTCCTCTGGGTCGCCACGTACC TCGGCTCTTCGCCGCCCCTTCCCGCCTTTAAAGCCCTCTCACCTACTCCTGTCTCGGCATGTT ACTTTCTGCACTTGCTTAACTCCAAGCATCACGTAACTACCTTCTCTGTACATAAAAGGGAGA GCATTCGTCI 1 ILICACTCACTATTCAACTCCATGGTTCCCTGGGTAATTAGGCGATACCTTG AGCACCTGCTAATTATGGGCCAGCGCGGTGCTGGATTCTGAGGAAGGTGCTGAGTAACTTG AAGACTAGTTCACTGCCTGCCAGGAGCTAAAGGGACGAGGGGTGGAAGpARBI- 948:SERF2_1_ Endogeno us_52 CCGGGTTAGGCATAGGCCCTCCCGGATCTTCCGCGGTGTAAGGAGAAGGCCAGCGCCCCT GTGATAGGCCCAGAGCCCCCACTCCACAAGCCAGCCCATCCCCCACGGAGACCCAAACCGT CCACACACACCTTGCCAGCTGTTTGGGCCCCACGCCGCCCCAAAACACGCCTCCAGCTGGCC CCTTGGGACCTCCCTTCTCTAGTCCGTATTTTGACCTGGCCCGTGGCAGATTCGCCACTCCCC CCTACCCCAAGCAGCCTGGGCCTCGATGGGCCGTTGTCGGGGCCCGGAGATTGAAGTGGT GTTGGATCCTGCTGCTGGCCGCGCTGGGGTAGAAGGGTCGCCGGTGTGTGGGCAGAGCG GCCCCCGCGTCTCACCTTTAATTTTCTTTCCTTAGGCGGTAACCAGCGTGAGCTCGCCCGCCA GAAGAATATGAAAAAGCAGAGCtccggatccggagagggcaggggatctctccttacttgtggcgacgtgga ggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCT GGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGG GCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGT GCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCG ACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCG CACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGC GACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATC CTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGC AGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGC AGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGA CAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCAC ATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACA Aatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcact gcattctagttgtggtttgtccaaactcatcaatgtatcttatGACTCGGTTAAGGGAAAGCGCCGAGATGA CGGGCI 1 ILIGCTGCCGCCCGCAAGCAGAGGTAGCCCCAGGGAGGGGAGGGAAAGGGAC GGTGGAGACCTGGGTTAGACCAAGGGTTATAGAAGGAAAGAGAGCTACCTCAGGGCTTGA ATGTGGACTAGTCGTGAGGAGCAGAGTGCATTGCTTCCTCTAGGGTTTTATTTCCTCCCCAC CCTCCAAATTGTTAGCTCACAGCCTTACAGGAAAGGACGGGGGCGGGCGCCTGCCCTCAGT CTGAI 1 ILIGAGCGTCCCTGGGTCTGACCTTAAGGGCAAGGGCAGGGAGCTTCACATTTCA AATACAGTTGTGGTTACGGCAGCCCAGTACTTTTGGCCCTCCTTGCTGTTCGGTTCTCCTCCCTTCTCCCAACCTCCTC ACTG GTGTTG CTG G GTGTG GTCCTCAATACAG AATAG AG 1806 pARBI- 949: SERF2_2_ Endogeno us_53_54 AATCGAGCCCTTTGCCCACGGCTACTTCACGGGACCACCCTCCCGGGTTAGGCATAGGCCCT CCCGGATCTTCCGCGGTGTAAGGAGAAGGCCAGCGCCCCTGTGATAGGCCCAGAGCCCCC ACTCCACAAGCCAGCCCATCCCCCACGGAGACCCAAACCGTCCACACACACCTTGCCAGCTG TTTGGGCCCCACGCCGCCCCAAAACACGCCTCCAGCTGGCCCCTTGGGACCTCCCTTCTCTA GTCCGTATTTTGACCTGGCCCGTGGCAGATTCGCCACTCCCCCCTACCCCAAGCAGCCTGGG CCTCGATGGGCCGTTGTCGGGGCCCGGAGATTGAAGTGGTGTTGGATCCTGCTGCTGGCC GCGCTGGGGTAGAAGGGTCGCCGGTGTGTGGGCAGAGCGGCCCCCGCGTCTCACCTTTAA TTTTCTTTCCTTAGGCGGTAACtccggatccggagagggcaggggatctctccttacttgtggcgacgtggagg agaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGG TCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGC GATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGC CCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGAC 1806 WO 2022/093846 PCT/US2021/056689 CACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCA CCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCG ACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCC TGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCA GAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCA GCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGAC AACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACA TGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAA atgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactg cattctagttgtggtttgtccaaactcatcaatgtatcttatCAGCGCGAGCTTGCCCGCCAGAAGAATATG AAAAAGCAGAGCGACTCGGTTAAGGGAAAGCGCCGAGATGACGGGCI 1 ILIGCTGCCGCC CGCAAGCAGAGGTAGCCCCAGGGAGGGGAGGGAAAGGGACGGTGGAGACCTGGGTTAG ACCAAGGGTTATAGAAGGAAAGAGAGCTACCTCAGGGCTTGAATGTGGACTAGTCGTGAG GAGCAGAGTGCATTGCTTCCTCTAGGGTTTTATTTCCTCCCCACCCTCCAAATTGTTAGCTCA CAGCCTTACAGGAAAGGACGGGGGCGGGCGCCTGCCCTCAGTCTGAI 1 ILIGAGCGTCCCT GGGTCTGACCTTAAGGGCAAGGGCAGGGAGCTTCACATTTCAAATACAGTTGTGGTTACGG CAGCCCAGTACI 1 1 1GGCCCTCCTTGCTGTTCGGTTCTCCTCCCTTCTCCCAACCTCpARBI- 950: SLC38A1_ lEndoge nous_55 TTCAAAAGGAATC1 HUGH 1 CAACTATTAGGATC1 1 1 1 1AAATCAAATATGTA1 1 1 IAATG GTGTACACCAGACCTGAAGAAAAAGATCACAGAAGGAATTTCCCCTTTGTAAGATAGAGGT AGTTAAAAATAAGCCTTATGACCTAATAGGTTAATTGTAATGCTCTGGTAGCCAACTTGAAA AAGGAGAAATGATGGTTGCATCTCACATTTTAAAATGTTAAGAATTTGTTTTGTAATGAGGA TACCTTAACCCCTGAAGGCCAAAATGACTATTTGTGTGAGTTTGAGAAAGGCACATAGTAA CTTGGGGAACAGTCAATAGAATGACAAAATCTTGACTATTTTAACI 1 1 L1GAACCCTGTCAT TTCTTGTGTTCTCAAATTTGAI 1 1 1 1AAATAGGCTGCATGGTGTATGAAAAGCTGGGGGAAC AAGTCTTTGGCACCACAtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaac cccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGA GCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATG CCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTG GCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACA TGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCAT CTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACAC CCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGG GCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAG AACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTC GCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACC ACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGT CCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgat tgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattc tagttgtggtttgtccaaactcatcaatgtatcttatGGGAAGTTCGTAATCTTTGGAGCCACCTCTCTACA GAACACTGGAGGTAAAAAGAACATGCTTTTCTTTACATAACTTGAAACTAATTCTGGTGGAT GAGCGGCCACATGAATTTTAACATAATTCAAGCAGTTATCATCCTCATTGCTAAAATGGCAC AGGGAAAGTAAAGCAGAGACAGCAGTCACTTATTTAAAGCCACAAATCCTGCTAGAGTAGC TGAAGTTGCCTTTGTGTCTTACTGACAGTTGGTCTAAGAACGGGCTGATAAC1 1 1 1 IATGTA GCTTGCAACATAAGCCTTCGTATCTTCTTTCTAAAAATGTTCTCATTTTCCTTCAGCAATGCTG AGCTACCTCTTCATCGTAAAAAATGAACTACCCTCTGCCATAAAGI 1 ILIAATGGGAAAGGA AGAGACATTTTCGTAAGTTATAGACCAI Hill IATGATATA 1806 pARBI- 951: SLC38A1_ 2_Endoge nous_56_ TAAAGATGTCAAGCTTCAAATCATTATCATAAGGTTAAATATATTACGCATGTCTTTACAGCA AGTTTATTTCTGATCGTGAAAGTAGAAGAAGTCTCACAAACAGCCATTTGGAAAAAAAGAA GTGTGATGAGTATGTAAGTATCATTATAATGAAGTATGCTTATTTTTTTAATCATATAAATTG GGACAAATCI 1 1 1 1AATTCAAGTAGCATAGTACCAAAAGCATAACTACCTGTATTCACCAGG ATATTCCTCATACCTTATGTATTTICTCTTGAAATCCATTCAAGGAAATAACTAGATAACTAA GAATGGATTTTCTTGAATTTTACTTCCATATTGGTTCCTGAGAGTGCATTAAAGGCTTTGGCT TGATGAACTTTCTTGGGGATTATTTTGCTTAGTGTCAATGTTTGTTTCTTTGTTCAGATTCCA GGTACAACCTCCtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggcc ccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGG 1806 WO 2022/093846 PCT/US2021/056689 ACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCT ACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCAC CCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAG CAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTT CAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGT GAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAA GCTGG AGTACAACTACAACAG CCACAACGTCTATATCATG GCCG ACAAG CAG AAG AACG G CATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGAC CACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACC TGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCT GGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattg cagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtg gtttgtccaaactcatcaatgtatcttatTTAGGCATGTCAGTTTTTAACCTAAGCAACGCCATTATGGG CAGTGGGATTTTGGGACTCGCCTTTGCCCTGGCAAACACTGGAATCCTACI 1 1 1 ICTGTGAG TATTGACGTGCCGGTACTTTCCATTTTAAAACTGAACIIIIIGIAIGIIILI GTTATTACATAG AAGAAATGTGAAATATTTATAAATAGTTTTTTTATTAACTTGGCTAAGTTACAAGTACATACT TTGATATTTATTGCTTGAGTGATTTTCCAAACTGTACCTAATGCTTACAACAAAGAGGAAGG AGAAAATCI 1 1 1 1ATTAATCAAAAATACTGAAATAAGCATTTGTGAAAAGGATTAAAACATT TGAAAATAACI 1 1 1 1 1 IGG 1A1 1 1 1 1GGAGTCTACCTGTGACTTTAAATCTCAGTTAAAATAT TAAGAGGTGTTTAACCCCAGCCAGTCACCACTTpARBI- 952: SMAD2_1Endogen ous_58 ATCATTCTTCACACTAGTTCCI 1 1 1L1 GACTCTTCAGTCACCTCCAGAATTAATATCCTTAGAA GCATCTCTAAAATGAGTTTGATTTACTAAACATAGAAGTTGACAAAG Hill CAAGTATAAC TGCATAAACTCTCI Illi IAAAAAAICAGI 1 1 1 1 CCCAAGTTGTTAGCCTTTCATTGGCATTTG AGTCATTTATGTGACATATTTATAAGAAACATCTGCTAGTGCTGCTGCATACTTTTATCAGAT CCATTAAATAGTACAI 1 1 1 1 GTTCTTGATTCTCACTAAAACTAACTAAATGGCTGTCATTCTTT TCTTTATGCTTTTATTGTACTAATTTAGCCCATTTGACTGCACllllllllllllllllll AAAGTTCCCT CCTTTCTTTTCCCCTTGCTTCCCAACAGGTCTCTTGATGGTCGTCTCCAGGTATCCCATCGAtc cggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggccccATGGTGAGCAA GGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAA CGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGAC CCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCC TGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTC AAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCA ACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGC TGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACT ACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTT CAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAA CACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCC AAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACC GCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttac aaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatca atgtatcttatAAAGGATTGCCACATGTTATATATTGCCGATTATGGCGCTGGCCTGATCTTCAC AGTCATCATGAACTCAAGGCAATTGAAAACTGCGAATATGCTTTTAATCTTAAAAAGGATGA AGTATGTGTAAACCCTTACCACTATCAGAGAGTTGAGACACCAGGTAGGAATATTGCAAGT TTTTTTCTTGGTTTTGAATTAAATGCCTGAACTTCAGTATATTTAAGTACTCTTGTGACCCAG GAAAATTTTAGTGTAAATTCTAATAAATTACCTTAAATTGTGCATATTATTTGGTGGTAATTA AAAtttttttatttttaaaaatttttAATGAGAAAACATATCTGTTTCTTGGAATAGCATATGATTTGG CATGAAAGTGCATATCCAGGAAATCCTGTAGATTGGCAGTCTGCTCAGCGCTATGCTGATG TGCTTCTACATGTCCCT 1806 pARBI- 953:SMAD22Endogen ous_59 TTCTATATTAAAAATCAGTTGACATCTG Illi 1AGATAAI Illi 1AAAAAACTGGATTATAAA ATGAAGCACTTAGTAAAGCTGATGGCAGAGGTTTTAGATCTTTTGAATACAGGAAAGTGGT AAGGGCATTATAGGTATGATTCATTGAGCTAGAGGGCGTTGGTGTTCACATTTTAAAAACA TAATCATGACTTATCTGGAGTCACATGTTCCATTTTATTGGCTTCCTTCATATAGAAAATATA GTAACCAGCACTACATGCCTGTGAAAAAGTGAAGCAATTGTATATITICTGGGTGAAGGAA GTATTCTGTACATTCTCCATGTTTTACATCATGGTATTTTGAATAACCATGCTTCCATGTTCAC 1806 WO 2022/093846 PCT/US2021/056689 ATCAAI 1 1 1 1 IGI 1 1 1 1 CAATTTATGCACAGCACTTGCTCTGAAATTTGGGGACTGAGTACAC CAAATACGATAGATtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccg gccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCT GGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCA CCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCC CACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGA AGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTT CTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCA CAAG CTG G AGTACAACTACAACAG CCACAACGTCTATATCATG GCCG ACAAGCAG AAG AAC GGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCC GACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACT ACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCT GCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgttt attgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagtt gtggtttgtccaaactcatcaatgtatcttatCAGTGGGATACAACAGGCCTTTACAGCTTCTCTGAACA AACCAGGTGAATATTCTGCCCTCTGTCGAATCTTAGAGATCTTGTGGGAGGGGGGTATATT TTG AAAG ACCTATATG G G GTTG CTTAGTATAATTTTG CCTAG G ATGTTTCCTTAATGTAAAA TAAG G CATAG CATTTAAA ATATCTG CTTG CCAGTATAAAAAATATATTAAATGTTTCAG CTG ATGTTTTAATCAATGCAATTCTAGTTTGAATCTTCTTTAAATTACTGTATCCCCTAAAGAATA ATAATTTTGATAACTATATATTTATTTTAGCTTGAGATCAGATTATAATCTGTTGTTGGCCTA Al 1 1 1 1AAGTAGATACATGATGAGTTTTGCTAAATTTCTTGTTATCAGAATCTCATCTTTATAC TAATAAATACATACTTAATGAACCCCTTATATCACAApARBI- 954: SMAD23Endogen ous_60 TCAATGTAI 1 1 1 IGTATAGTCTI 1 1 GAGATTAGAGTGAAGTTCTAAAAAGTAAGAGAACCTT TTGTGAAAATATTTTAATTGACACTACTAAGAGTTTAAAATAGTATTGGTGGTGAAAAATCG TTAAAAGTATCTGATTTTACTTGCAAAATTACTGTATTTTCCCACAAGAGGAGTCCTTACAAC ATTCTTGI 1 1 1 1AGAAGGGTTTGTTTCCATCATTCATTTAAATTCATAAAGATAACGTTTTCAT GGGTGGAGAAGTCTATTGGGAAAGTCATAATTCGAAI 1 ILIATCTTGCTTTGCAGTTTGCTT TCTATGATAAGTTGAAATTATTACTTGATGTTCAAGGTAGTCTCTACATCATCCTTTCAATAT TTCTGCTAGGTTCGATACAAGAGGCTGTTTTCCTAGCGTGGCTTGCTGCCTTTGGTAAGAAC ATGTCGTCCATCtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggcc ccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGG ACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCT ACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCAC CCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAG CAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTT CAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGT GAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAA GCTGG AGTACAACTACAACAG CCACAACGTCTATATCATG GCCG ACAAG CAG AAG AACG G CATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGAC CACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACC TGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCT GGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattg cagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtg gtttgtccaaactcatcaatgtatcttatTTGCCATTCACGCCGCCAGTTGTGAAGAGACTGCTGGGAT GGAAGAAGTCAGCTGGTGGGTCTGGAGGAGCAGGCGGAGGAGAGCAGAATGGGCAGGA AGAAAAGTGGTGTGAGAAAGCAGTGAAAAGTCTGGTGAAGAAGCTAAAGAAAACAGGAC GATTAGATGAGCTTGAGAAAGCCATCACCACTCAAAACTGTAATACTAAATGTGTTACCATA CCAAGGTAAGTTTTGTTAGATCCCAGGTTTGATCAAATTATGTCAAGGAATCTGAAGGAAA GTTACTGAATTTGTGTTCCTTTCAAGTTGCCTGTAAAAAGTGATGATTGAAATATGACTGTTT TTAACCTTGTATAAATTG 1 1 1 1 1 GCTAGCTGACTTGTTTTATAAATTATTTTCTTGAATAGTGA GGTTTAATCAAGCTAAATAAGATACTTAGATTTATTATCTTCA 1806 pARBI- 955: SOCS1_1 GGGCTCCCGCAGCACAGCCI 1 ILICCGGCCCTAGCCCAAATCGCCCAGACCAGGCGCGGAT CCCAGCCTGGCCAGCAGGCGGCGGGCGCGGGGCGGCGAGCCGGGGCCGGACGGCTGGA GCCAGAACCGGCTGCTCTCCACGCCCCCCTCTCGGTGCTGCCCGGAGGCCGGACTCCGCCT 1806 WO 2022/093846 PCT/US2021/056689 Endogen ous_61CCACCGAGCCCCCACCCGCCGGGAAGAGCTCCGCGGAGTACAGAGCCCAI 1 1 ILIAGCTGT GTCCACTGAGGCTGAACGGATCCGCGCGGACTTGGTGCTCCGTGCTCGCCCCCTAGGGCCG GGTCCGCCGGGAGCGCCGCCCTCCGGAGTTGTCCGGCCGGCGCACACCTGCCCGGCCCCG CAGCGCCCCAGCTCACCTCTTTGTCTCTCCCGCAGCGCACCCCCGGACGCTATGGCCCACCC CTCCGGCTGGCCCCTTCTGTAGGATGtccggatccggagagggcaggggatctctccttacttgtggcgacg tggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCAT CCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGA GGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCC GTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCC CGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAG CGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGG GCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACA TCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAA GCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGT GCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCC GACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGAT CACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGT ACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattttttt cactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGTAGCACACAACCAGGTGGCAGCCGA CAATGCAGTCTCCACAGCAGCAGAGCCCCGACGGCGGCCAGAACCTTCCTCCTCTTCCTCCT CCTcgcccgcggcccccgcgcgcccgcggccgtgccccgcggtcccggccccggCCCCCGGCGACACGCACTT CCGCACATTCCGTTCGCACGCCGATTACCGGCGCATCACGCGCGCCAGCGCGCTCCTGGAC GCCTGCGGATTCTACTGGGGGCCCCTGAGCGTGCACGGGGCGCACGAGCGGCTGCGCGCC GAGCCCGTGGGCACCTTCCTGGTGCGCGACAGCCGCCAGCGGAACTGCI 1 1 1 ICGCCCTTA GCGTGAAGATGGCCTCGGGACCCACGAGCATCCGCGTGCACTTTCAGGCCGGCCGCTTTCA CCTGGATGGCAGCCGCGAGAGCTTCGACTGCCTCTTCGAGCTGCTGpARBI- 956: S0CS12Endogen ous_62 GGATCCCAGCCTGGCCAGCAGGCGGCGGGCGCGGGGCGGCGAGCCGGGGCCGGACGGC TGGAGCCAGAACCGGCTGCTCTCCACGCCCCCCTCTCGGTGCTGCCCGGAGGCCGGACTCC GCCTCCACCGAGCCCCCACCCGCCGGGAAGAGCTCCGCGGAGTACAGAGCCCATTTTCTAG CTGTGTCCACTGAGGCTGAACGGATCCGCGCGGACTTGGTGCTCCGTGCTCGCCCCCTAGG GCCGGGTCCGCCGGGAGCGCCGCCCTCCGGAGTTGTCCGGCCGGCGCACACCTGCCCGGC CCCGCAGCGCCCCAGCTCACCTCTTTGTCTCTCCCGCAGCGCACCCCCGGACGCTATGGCCC ACCCCTCCGGCTGGCCCCTTCTGTAGGATGGTAGCACACAACCAGGTGGCAGCCGACAATG CAGTCTCCACAGCAGCAGAGCCCCGAtccggatccggagagggcaggggatctctccttacttgtggcgacg tggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCAT CCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGA GGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCC GTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCC CGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAG CGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGG GCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACA TCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAA GCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGT GCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCC GACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGAT CACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGT ACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattttttt cactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCGGCGGCCAGAACCTTCCTCCTCTTCCT CCTCCTcgcccgcggcccccgcgcgcccgcggccgtgccccgcggtcccggccccggCCCCCGGCGACACGCA CTTCCGCACATTCCGTTCGCACGCCGATTACCGGCGCATCACGCGCGCCAGCGCGCTCCTGG ACGCCTGCGGATTCTACTGGGGGCCCCTGAGCGTGCACGGGGCGCACGAGCGGCTGCGCG CCGAGCCCGTGGGCACCTTCCTGGTGCGCGACAGCCGCCAGCGGAACTGCI 1 1 1 ICGCCCT TAGCGTGAAGATGGCCTCGGGACCCACGAGCATCCGCGTGCACTTTCAGGCCGGCCGCTTT CACCTGGATGGCAGCCGCGAGAGCTTCGACTGCCTCTTCGAGCTGCTGGAGCACTACGTGG CGGCGCCGCGCCGCATGCTGGGGGCCCCGCTGCGCCAGCGCCGC 1806 WO 2022/093846 PCT/US2021/056689 pARBI- 957: S0CS13Endogen ous_63 CGGACTCCGCCTCCACCGAGCCCCCACCCGCCGGGAAGAGCTCCGCGGAGTACAGAGCCC ATTTTCTAGCTGTGTCCACTGAGGCTGAACGGATCCGCGCGGACTTGGTGCTCCGTGCTCGC CCCCTAGGGCCGGGTCCGCCGGGAGCGCCGCCCTCCGGAGTTGTCCGGCCGGCGCACACC TGCCCGGCCCCGCAGCGCCCCAGCTCACCTCTTTGTCTCTCCCGCAGCGCACCCCCGGACGC TATG G CCCACCCCTCCG G CTG G CCCCTTCTGTAG G ATG GTAG C ACACA ACCAG GTG G CAG C CGACAATGCAGTCTCCACAGCAGCAGAGCCCCGACGGCGGCCAGAACCTTCCTCCTCTTCCT CCTCCTcgcccgcggcccccgcgcgcccgcggccgtgccccgcggtcccggccccggCCCCCGGCGACACGCA CTTCCGCACAtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggcccc ATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGAC GGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTAC GGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCC TCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCA GCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCA AGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGA ACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGC TGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCAT CAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCA CTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTG AGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTG GAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgc agcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggt ttgtccaaactcatcaatgtatcttatTTCCGTTCGCACGCCGATTACCGGCGCATCACGCGCGCCAGC GCGCTCCTGGACGCCTGCGGATTCTACTGGGGGCCCCTGAGCGTGCACGGGGCGCACGAG CGGCTGCGCGCCGAGCCCGTGGGCACCTTCCTGGTGCGCGACAGCCGCCAGCGGAACTGC Illi 1CGCCCTTAGCGTGAAGATGGCCTCGGGACCCACGAGCATCCGCGTGCACTTTCAGGC CGGCCGCTTTCACCTGGATGGCAGCCGCGAGAGCTTCGACTGCCTCTTCGAGCTGCTGGAG CACTACGTGGCGGCGCCGCGCCGCATGCTGGGGGCCCCGCTGCGCCAGCGCCGCGTGCGG CCGCTGCAGGAGCTGTGCCGCCAGCGCATCGTGGCCACCGTGGGCCGCGAGAACCTGGCT CGCATCCCCCTCAACCCCGTCCTCCGCGACTACCTGAGCTCCTTC 1806 pARBI- 958: SRP14_1_ Endogeno us_64 GGCAGACAAACAGTTAAAACAGAGGAGTGGGGTAAGTGATGACCTAACCCAGCCCCGCTG CTCTAGTTTTGTTAAACACCTCATCTGCTATCACGGTCTGGCGAAACCCTGGAGAAACTATT ATTTCCACGACGGAAACATGTAATATCGAAGCACGTTAAATTCCACTCAAAGTGGCGGCGT CTGGGATCCCTGACAAAGAGCCCTGGGCTGCTTGGGGCCCATTGTTACCAGAAGCAACCTA GGCGGCTCAGTGCTGGGGACTGAGCCAGCTACAATCCCTACTATTTTCCGGGCCCGAAGCC CCGAATGTGCTCAGTACAGGGTGGGGAAAGGTAGAGGAAGGCGGCGGTCCGCGGCAGAC AGACTCCGGTGGCTCCCAGACACCGGGAACCCAGGGAGCATCGCCCGGCTCCCCTCCCGCT GCTTACACTTCTTCAAGGTGATATAtccggatccggagagggcaggggatctctccttacttgtggcgacgtg gaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCC TGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAG GGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCG TGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCC GACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGC GCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGG GCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACA TCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAA GCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGT GCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCC GACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGAT CACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGT ACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattttttt cactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGACGCTGCCCGACGTCCGGCACTTCTG GAAAAGTCTGGTCAGCTCCGTCAGGAACTGGAAAACAACAGGCCCAGCCCCGTTAGCCAG CCCCAAATCCTCGTCCTGCCGCGTCAAGGCCCTGGTCCTCCTGCAGGAGGCACAGGTCTCG AGTAACGCCTGAGCCGCCCCCTTCCCTCGGCCGGCCAGGCCTAGCCATACCTGCTCGCTCTC CAACAACACCATCGCGGCGACGCTGGCTCGACTCCCTCCGCTTAAGCCCCTAGCAGTGAGA 1806 WO 2022/093846 PCT/US2021/056689 GCCGGAAGTTCGGCCTAGGCTGGGCGGGACTTCCGCTACTAGACTTCCATTGTCTTCCACCA ATCTCTTCTCTTCCACCAATCCCGGCCTGCGCCCTCCCCCCTCCCCGCCCGCCTAGCGCCCGC GCCCTGGGACGTCCGGGGGCCTGTGACCCGGAGGCGCTGGGGCTGTCCTGGGTCpARBI- 959: SRP14_2_ Endogeno us_65_66 GTCTGTCTGCCGCGGACCGCCGCCTTCCTCTACCTTTCCCCACCCTGTACTGAGCACATTCGG GGCTTCGGGCCCGGAAAATAGTAGGGATTGTAGCTGGCTCAGTCCCCAGCACTGAGCCGC CTAGGTTGCTTCTGGTAACAATGGGCCCCAAGCAGCCCAGGGCTCTTTGTCAGGGATCCCA GACGCCGCCACTTTGAGTGGAATTTAACGTGCTTCGATATTACATGTTTCCGTCGTGGAAAT AATAGI 1 ILICCAGGGTTTCGCCAGACCGTGATAGCAGATGAGGTGTTTAACAAAACTAGA GCAGCGGGGCTGGGTTAGGTCATCACTTACCCCACTCCTCTGTTTTAACTGTTTGTCTGCCG CTCAGCCACGTACGCGGCCGTGTTCACCAGGATGCATTTTTTCCTTCAGATGACGGTCGAAC CAAACCCATTCCAAAGAAGtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggag aaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTC GAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGA TGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCT GGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCAC ATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCA TCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACA CCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGG GGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAA GAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCT CGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAAC CACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATG GTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatg attgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcat tctagttgtggtttgtccaaactcatcaatgtatcttatGGTACTGTGGAGGGCTTTGAGCCCGCAGACAA CAAGTGTCTGTTAAGAGCTACCGATGGGAAGAAGAAGATCAGCACTGTGGTGAGCTTAATT TCTAAGGCTGTCTTTTGAAATGTAAAGACTTGAACTTAACAGAGGATGGGGCG 1 1 ILIGAA CCAGGCTTTTATTTG 1 1 1 1 1CCC1 1 1 1GCCC1 G 1G 1 GGC1A1 1 1 1 1 GAGACCAGGACCTTCCTA TACTTTAGTAGTGGAAACCTCAAGAATAAAATAAGAAGGTAGAGGTCAGACAGTCGTTAGT TCTGCTAAAGCTCTTGTGGAAATGAAAGTAGCATATTGGTCCTTATTCGTAGTACTGTAAGG AGCAG CTG G CATAAATATTTG ATTCCTTAG CCCCTTACTGTG CTG G G CCTTCAATAAG CAGT TTCTTGGTACCAGGTGATGCTATTATTTCCTTATCTTTGTGGTTCAC 1806 pARBI- 960: SRSF9_1_ Endogeno us_67 CCCACGTCAGTGAGTGCTCACAAGTCTGTGAGGTAGGCGGCGCCACAGAGAGAAACTGAG GCGCGGGAGCCCAAGCCACTTGTCCAGCGCCTCAGCCGAGCGCGAACCGCGCTCGGGGAT GGCATCCACACGGCCCGGCCCCAGGCTCTCCCTGTCAGCGCCCGAAGGCCCTTCGCACCTC CAGGGGGCGCCGGCCTGCGCGCACGCGCAATGGTCGCAGCCGCGTTCTCTTTAAGAGGAC TCCTTTTGCCTCCGCCGACCCCTTCGCTTCCGCTCCGCGTTCCCACAATGCAGTGCGGCTGAG CGCCTCGGAGCCCGCGGGGACGCTGCGGGGGGACCCGTGCTGAggcggcggcggcgacgtgggc tgcggcgggcccgcggcgtcgggcggtgcggatgtcgggctgggcggacgagcgcggcggcgAGGGCGACGGG CGCATCTACtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggccccA TGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACG GCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACG GCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTC GTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGC ACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAG GACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAAC CGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTG GAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCA AGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTA CCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGC ACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAG TTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagctt ataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtc caaactcatcaatgtatcttatGTGGGGAACCTTCCGACCGACGTGCGCGAGAAGGACTTGGAGGA CCTGTTCTACAAGTACGGCCGCATCCGCGAGATCGAGCTCAAGAACCGGCACGGCCTCGTG 1806 WO 2022/093846 PCT/US2021/056689 CCCTTCGCCTTCGTGCGCTTCGAGGACCCCCGGTGAGGcccccgcgcccctgccctctcctcctcggtgc ctgaggcccccgccttccctgctgtcccctcccccagggctcccctccccccggcctcccctccccccgcctccgcgcaga cccctcaCGGCGCCCCCTCACGGGTGGAGGATGAGGCAGCCTCTCCTCGCAGGCCCGGGCCG TCCTTCGCGCCGTCGTCACTTCCTTTA1 1 1 1 1ATTATTCCAATATTTTACTTAGAAACCCAAAA GCTGAGCCTTTGGAGGGCCCAAGCCCGCCTGCACCGGCCTCGGGGGGTCCAAATGAGCCT TGTCCGCCpARBI- 961: SRSF9_2_ Endogeno us_68 TGTGGTGTGCTTTTCGAGAAAATGCTCACGAAGATTAGAAAAACACTGATGGTTTATTGGC AAAATCAATAATCTGTCAGCAGTTGATTCttttttttEFCTGAATTAGCCCTCTTATGAGTAATCT GTTTGCTCATTCATTATAATTTCATACCTCTAAAACTGCGTGTGACAGCTGTAAAGGTTAATT CCAGTATCATGAAACGTCTCCAAACCAAAGCAGAAGTGCTTCAGGATCCTGATTTGTGTGTT Illi 1CTTCACTCTAGGTTTCCCTTTTATGCTTACTACTCATGCCCCTCACTTGGAAAGTCACT TGGCCTCCTGAACAGCACTAACTCCAAACGttttttttgttgttgttgttttttttAGAGATGCAGAGGA TGCTATTTATGGAAGAAATGGTTATGATTATGGCCAGTGTCGGCTTCGTGTGGAGTTCCCCA GGtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggccccATGGTGA GCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGAC GTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAG CTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGAC CACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGAC TTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGA CGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCAT CGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTA CAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTG AACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGC AGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCA GTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGT GACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatg gttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaact catcaatgtatcttatACTTATGGAGGTCGGGGTGGGTGGCCCCGTGGTGGGAGGAATGGGCCT CCTACAAGAAGATCTGATTTCCGAGTTCTTGTTTCAGGTATGTTCCTTTCAAACAGaatgagat gatacatgtaaaatacttaacacagagtctgtcttccaagaaatgatagctgttattcttCAGTGCATGGGACACG GGGGCTTTCTTTTCAATAGCCTGTGTGAAGCCTTGCCCTGGATTGCCAATGAGGAAAGTATC CTGCAAATGAAATTGCGCTGGGAGTGCAGCCTTGGAAGAACATAACCATATTTCTTGTAAA GGAGTTIICTAGTGGTGAGAAGGAAAGATGATGGGAAAACTTGAGCTACAATTCTAAAGA TGCTTCTTTTGGAATATACTTGGCATCAGACATGGTAGAAAGGCATTCAAGGAGCCAGATTT GAACAACTTACCCAGCC 1806 pARBI- 962: SRSF9_3_ Endogeno us_69 GATGGCATCCACACGGCCCGGCCCCAGGCTCTCCCTGTCAGCGCCCGAAGGCCCTTCGCAC CTCCAGGGGGCGCCGGCCTGCGCGCACGCGCAATGGTCGCAGCCGCGTTCTCTTTAAGAG GACTCCTTTTGCCTCCGCCGACCCCTTCGCTTCCGCTCCGCGTTCCCACAATGCAGTGCGGCT GAGCGCCTCGGAGCCCGCGGGGACGCTGCGGGGGGACCCGTGCTGAggcggcggcggcgacgt gggctgcggcgggcccgcggcgtcgggcggtgcggatgtcgggctgggcggacgagcgcggcggcgAGGGCGAC GGGCGCATCTACGTGGGGAACCTTCCGACCGACGTGCGCGAGAAGGACTTGGAGGACCTG TTCTACAAGTACGGCCGCATCCGCGAGATCGAGCTCAAGAACCGGCACGGCCTCGTGCCCT TCGCCTTCtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggccccAT GGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACG GCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACG GCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTC GTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGC ACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAG GACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAAC CGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTG GAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCA AGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTA CCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGC ACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAG TTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagctt 1806 WO 2022/093846 PCT/US2021/056689 dlddlgglldLdddldddgLddldgLdlLdLdddlllLdLdddldddgLdlllllllLdLlgLdllLldgllglgglllglL caaactcatcaatgtatcttatGTGCGCTTCGAGGACCCCCGGTGAGGcccccgcgcccctgccctctcctcc tcggtgcctgaggcccccgccttccctgctgtcccctcccccagggctcccctccccccggcctcccctccccccgcctccg cgcagacccctcaCGGCGCCCCCTCACGGGTGGAGGATGAGGCAGCCTCTCCTCGCAGGCCCG GGCCGTCCTTCGCGCCGTCGTCACTTCCTTTAI 1 1 1 1ATTATTCCAATATTTTACTTAGAAACC CAAAAGCTGAGCCTTTGGAGGGCCCAAGCCCGCCTGCACCGGCCTCGGGGGGTCCAAATG AGCCTTGTCCGCCTCCTGCCTGGGGCAGCACCGTAGGGGGAAGCGGCCGCGGGGCAGCGC GGGGGTCGCCGTTCGCCCTTCCCGCTCGCCTCTCCCCCGGCCCGTGCTCGCCGTGGCTGGA GAGCAAGCTpARBI- 963: SUB1_1_ Endogeno us_70 GTAACTGACTAGCCTTAGTAGACTGTGGTTTCCAGGTTTATTCAGAAGTAGCAAGATCCCTC CAtttttttttefACCAAAGAAATCGTATGTGGGATCCCAAACCACAAAATAACCGTTCCTGTGG TTAATACTACTATAATGCCTGAAGTGTCTTTTGGGATCCTGAGAACAGAGTTTGAAAACATT ACTAGACAGAAGGATTGGTTAGATTCATAGTTTTGTTGTTGAGTGAAACTTGCTTATGTATA TATTTATGATATTTTGGATGTAGTCTTTTGATTGTTTAAATCTTAAAAAGTAATGGGATCTTT TGACACTGGGGTATGTTTTA1 1 1 1 1A1G 1G 1GCAAA Illi AACCA1A1 1 C1 1 1 1L1AGTTAAA GAGGAAAAAGCAAGTTGCTCCAGAAAAACCTGTAAAGAAACAAAAGACAGGTGAGACTTC GAGAGCCCTGTCAtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccgg ccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTG GACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCAC CTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCC ACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAA GCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCT TCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGG TGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACA AGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACG GCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCG ACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTA CCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTG CTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgttta ttgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttg tggtttgtccaaactcatcaatgtatcttatTCTTCTAAACAGAGCAGCAGCAGCAGAGATGATAACAT GTTTCAGGTAAAGTTGGCTALLLLLLLLLLLLLLLLLLLLgacatggagtcatgctctgtcacccaggctggagtgca gtggcgccatctcggctcactgcaacctcagcctcctgagttcaagcagttctctgcctcagcctcccgagtagctaggat tacaggcatccgccaccagacctggctaatttttgtatttttagtagagatggggtttcaccatcttggccaggctggtctt gaactcctgaccttgtgatccaactgcctcagcctccaaaagtgctgggtttacaggtgtgagccaccatgccttgccAA AGTTGGCTGTTTCTTTAGATTCAGAGGAATTATTATCTGGCTTGATCTGAAGAATGTTAAAA GTACTATGATCTGATAATTGCCTAATATG 1806 pARBI- 964: SUB1_2_ Endogeno us_71 ATAAATAAACATATCCTGGAAATGGAATAAGTTGGTTATATTCI 1 1 1 1AATTAGTATATCTGC TTCGTAAAATAAGTAACTGACTAGCCTTAGTAGACTGTGGTTTCCAGGTTTATTCAGAAGTA GCAAGATCCCTCCAI 1 1 1 1 1 1 1 1 LI ACCAAAGAAATCGTATGTGGGATCCCAAACCACAAAAT AACCGTTCCTGTGGTTAATACTACTATAATGCCTGAAGTGTCTTTTGGGATCCTGAGAACAG AGTTTGAAAACATTACTAGACAGAAGGATTGGTTAGATTCATAGTTTTGTTGTTGAGTGAAA CTTGCTTATGTATATATTTATGATATTTTGGATGTAGTCTTTTGATTGTTTAAATCTTAAAAAG TAATGGGATCTTTTGACACTGGGGTATGTTTTAI 1 1 1 1ATGTGTGCAAATTTTAACCATATTC TTTTCTAGTTAtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaaccccggcccc ATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGAC GGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTAC GGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCC TCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCA GCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCA AGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGA ACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGC TGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCAT CAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCA CTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTG 1806 WO 2022/093846 PCT/US2021/056689 AGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTG GAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgc agcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggt ttgtccaaactcatcaatgtatcttatAAGAGGAAAAAGCAAGTTGCTCCAGAAAAACCTGTAAAGAA ACAAAAGACAGGTGAGACTTCGAGAGCCCTGTCATCTTCTAAACAGAGCAGCAGCAGCAG AGATGATAACATGTTTCAGGTAAAGTTGGCTAI 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 GACATGGAGTCA TGCTCTGTCACCCAGGCTGGAGTGCAGTGGCGCCATCTCGGCTCACTGCAACCTCAGCCTCC TGAGTTCAAGCAGTTCTCTGCCTCAGCCTCCCGAGTAGCTAGGATTACAGGCATCCGCCACC AGACCTGGCTAAI 1 1 1 1G 1A1 1 1 1 1AGTAGAGATGGGGTTTCACCATCTTGGCCAGGCTGGT CTTGAACTCCTGACCTTGTGATCCAACTGCCTCAGCCTCCAAAAGTGCTGGGTTTACAGGTG TG AG CCACCATG CCTTG CCAA AGTTG G CTGTTTCTTTpARBI- 965: SUB1_3_ Endogeno us_72 AATTAGTATATCTGCTTCGTAAAATAAGTAACTGACTAGCCTTAGTAGACTGTGGTTTCCAG GTTTATTCAGAAGTAGCAAGATCCCTCCATTTTTTTTTCTACCAAAGAAATCGTATGTGGGAT CCCAAACCACAAAATAACCGTTCCTGTG GTTAATACTACTATAATG CCTG AAGTGTCTTTTG GGATCCTGAGAACAGAGTTTGAAAACATTACTAGACAGAAGGATTGGTTAGATTCATAGTT TTGTTGTTGAGTGAAACTTGCTTATGTATATATTTATGATATTTTGGATGTAGTCTTTTGATT GTTTAAATCTTAAAAAGTAATGGGATCTTTTGACACTGGGGTATGTTTTA1 1 1 1 IATGTGTGC AAATTTTAACCATATTCTITICTAGTTAAAGAGGAAAAAGCAAGTTGCTCCAGAAAAACCTG TAAAGAAACAAAAGtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaacccc ggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGC TGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCC ACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGC CCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATG AAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCT TCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCC TGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGC ACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAA CGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGC CGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCAC TACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCC TGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgt ttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctag ttgtggtttgtccaaactcatcaatgtatcttatACAGGTGAGACTTCGAGAGCCCTGTCATCTTCTAAAC AGAGCAGCAGCAGCAGAGATGATAACATGTTTCAGGTAAAGTTGGCTAI 1 1 1 1 1 1 1 1 1 1 1 1 TTTTTTGACATGGAGTCATGCTCTGTCACCCAGGCTGGAGTGCAGTGGCGCCATCTCGGCTC ACTGCAACCTCAGCCTCCTGAGTTCAAGCAGTTCTCTGCCTCAGCCTCCCGAGTAGCTAGGA TTACAGGCATCCGCCACCAGACCTGGCTAAI 1 1 1 1G 1A1 1 1 1 1AGTAGAGATGGGGTTTCAC CATCTTGGCCAGGCTGGTCTTGAACTCCTGACCTTGTGATCCAACTGCCTCAGCCTCCAAAA GTGCTGGGTTTACAGGTGTGAGCCACCATGCCTTGCCAAAGTTGGCTGTTTCTTTAGATTCA GAGGAATTATTATCTGGCTTGATCTGAAGAATGTTAAAAGT 1806 pARBI- 966: TET21E ndogeno us_73 CACAI 1 1 I'AAI 1 1 1 1 G TTTCCATGCTC 1 1 1AGAATTCAACTAGAGGGCAGCCTTGTGGATGGC CCCGAAGCAAGCCTGATGGAACAGGATAGAACCAACCATGTTGAGGGCAACAGACTAAGT CCATTCCTGATACCATCACCTCCCATTTGCCAGACAGAACCTCTGGCTACAAAGCTCCAGAA TGGAAGCCCACTGCCTGAGAGAGCTCATCCAGAAGTAAATGGAGACACCAAGTGGCACTCT TTCAAAAGTTATTATGGAATACCCTGTATGAAGGGAAGCCAGAATAGTCGTGTGAGTCCTG ACTTTACACAAGAAAGTAGAGGGTATTCCAAGTGTTTGCAAAATGGAGGAATAAAACGCAC AGTTAGTGAACCTTCTCTCTCTGGGCTCCTTCAGATCAAGAAATTGAAACAAGACCAAAAGG CTAATGGAGAAAGACGTAACtccggatccggagagggcaggggatctctccttacttgtggcgacgtggagga gaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGT CGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCG ATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCC CTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACC ACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCAC CATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGA CACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCT 1806 WO 2022/093846 PCT/US2021/056689 GGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCA GAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCA GCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGAC AACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACA TGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAA atgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactg cattctagttgtggtttgtccaaactcatcaatgtatcttatTTCGGGGTAAGCCAAGAAAGAAATCCAGGT GAAAGCAGTCAACCAAATGTCTCCGATTTGAGTGATAAGAAAGAATCTGTGAGTTCTGTAG CCCAAGAAAATGCAGTTAAAGATTTCACCAG 1 1 1 1 1 CAACACATAACTGCAGTGGGCCTGAA AATCCAGAGCTTCAGATTCTGAATGAGCAGGAGGGGAAAAGTGCTAATTACCATGACAAG AACATTGTATTACTTAAAAACAAGGCAGTGCTAATGCCTAATGGTGCTACAG 1 1 ILIGCCTC TTCCGTGGAACACACACATGGTGAACTCCTGGAAAAAACACTGTCTCAATATTATCCAGATT GTGTTTCCATTGCGGTGCAGAAAACCACATCTCACATAAATGCCATTAACAGTCAGGCTACT AATGAGTTGTCCTGTGAGATCACTCACCCATCGCATACCTCAGGGCAGATCpARBI- 967: TET22E ndogeno us_74 AATGGAGAAAGACGTAACTTCGGGGTAAGCCAAGAAAGAAATCCAGGTGAAAGCAGTCAA CCAAATGTCTCCGATTTGAGTGATAAGAAAGAATCTGTGAGTTCTGTAGCCCAAGAAAATG CAGTTAAAGATTTCACCAG 1 1 1 1 1 CAACACATAACTGCAGTGGGCCTGAAAATCCAGAGCTT CAGATTCTGAATGAGCAGGAGGGGAAAAGTGCTAATTACCATGACAAGAACATTGTATTAC TTAAAAACAAGG CAGTG CTAATG CCTAATG GTG CTACAGTTTCTG CCTCTTCCGTG G AAC AC ACACATGGTGAACTCCTGGAAAAAACACTGTCTCAATATTATCCAGATTGTGTTTCCATTGC GGTGCAGAAAACCACATCTCACATAAATGCCATTAACAGTCAGGCTACTAATGAGTTGTCCT GTGAGATCACTCACCCATCGtccggatccggagagggcaggggatctctccttacttgtggcgacgtggagga gaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGT CGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCG ATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCC CTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACC ACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCAC CATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGA CACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCT GGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCA GAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCA GCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGAC AACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACA TGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAA atgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactg cattctagttgtggtttgtccaaactcatcaatgtatcttatCATACCTCAGGGCAGATCAATTCCGCACAGA CCTCTAACTCTGAGCTGCCTCCAAAGCCAGCTGCAGTGGTGAGTGAGGCCTGTGATGCTGA TGATGCTGATAATGCCAGTAAACTAGCTGCAATGCTAAATACCTGTTCCTTTCAGAAACCAG AACAACTACAACAACAAAAATCAG Hill GAGATATGCCCATCTCCTGCAGAAAATAACATC CAGGGAACCACAAAGCTAGCGTCTGGTGAAGAATTCTGTTCAGGTTCCAGCAGCAATTTGC AAGCTCCTGGTGGCAGCTCTGAACGGTATTTAAAACAAAATGAAATGAATGGTGCTTACTT CAAGCAAAGCTCAGTGTTCACTAAGGATTCCTIITCTGCCACTACCACACCACCACCACCATC ACAATTGCTTCTTTCTCCCCCTCCTCCTCTTCCACAGGTTCCTCAGCTT 1806 pARBI- 968: TET23E ndogeno us_75 GGAAAAAGCACTCTGAATGGTGGAGTTTTAGAAGAACACCACCACTACCCCAACCAAAGTA ACACAACACTTTTAAGGGAAGTGAAAATAGAGGGTAAACCTGAGGCACCACCTTCCCAGAG TCCTAATCCATCTACACATGTATGCAGCCCTTCTCCGATGC HILI GAAAGGCCTCAGAATAA TTGTGTGAACAGGAATGACATACAGACTGCAGGGACAATGACTGTTCCATTGTGTTCTGAG AAAACAAGACCAATGTCAGAACACCTCAAGCATAACCCACCAAI 1 1 1 1GGTAGCAGTGGAG AGCTACAGGACAACTGCCAGCAGTTGATGAGAAACAAAGAGCAAGAGATTCTGAAGGGTC GAGACAAGGAGCAAACACGAGATCTTGTGCCCCCAACACAGCACTATCTGAAACCAGGAT GGATTGAATTGAAGGCCCCTCGTtccggatccggagagggcaggggatctctccttacttgtggcgacgtgga ggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCT GGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGG GCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGT GCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCG 1806 WO 2022/093846 PCT/US2021/056689 ACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCG CACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGC GACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATC CTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGC AGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGC AGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGA CAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCAC ATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACA Aatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcact gcattctagttgtggtttgtccaaactcatcaatgtatcttatTTTCACCAAGCGGAATCCCATCTAAAACGT AATGAGGCATCACTGCCATCAATTCTTCAGTATCAACCCAATCTCTCCAATCAAATGACCTCC AAACAATACACTGGAAATTCCAACATGCCTGGGGGGCTCCCAAGGCAAGCTTACACCCAGA AAACAACACAGCTGGAGCACAAGTCACAAATGTACCAAGTTGAAATGAATCAAGGGCAGT CCCAAGGTACAGTGGACCAACATCTCCAGTTCCAAAAACCCTCACACCAGGTGCACTTCTCC AAAACAGACCATTTACCAAAAGCTCATGTGCAGTCACTGTGTGGCACTAGATTTCATTTTCA ACAAAGAGCAGATTCCCAAACTGAAAAACTTATGTCCCCAGTGTTGAAACAGCACTTGAAT CAACAGGCTTCAGAGACTGAGCCATTTTCAAACTCACACCTTTTGCAACATpARBI- 969: TIGIT_1_E ndogeno us_76 AAAGGGAGGTTGAGATGGGCTGAGGTCTTCTAGGAGGCGGGGAGGGAGTGCAGCCTTGA CAAGCCTCCCTGTGGGCGAGGTGTAAAGAGGGGCAGAAGTCAGCTCTGGAAGCATAGGGC AGTGGGTGGGGAGGAGATGGGCTGGGCTGGGCTGGAGTAGAGATGTGTGGAGAAGGGT GAGAAGACTGGAAAGACAACCTGAATGGGGGACTGGGAGCCTTGAATAACAGGCATGGA GAGGAGCGTCTCTTGAAATGGAAGAAACAGGAAATAATTACAGCCTCTATGGAGGAGCAA CAGGATGGACTGGAGAAACTATCATTCCAAAATCCAGTTGGGGCCTCAAAGGCCCTTAGAA Hill CTAGGAAGGTTGAAGGCCAGCTGCTGACCCAGGACTCACATGTGCTTCGTCCTCTTC CCTAGGAATGATGACAGGCACAATAGAAACAtccggatccggagagggcaggggatctctccttacttgt ggcgacgtggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGT GCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGA GGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAA GCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCC GCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGT CCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAA GTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATG GCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGAC GGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGC TGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAA GCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGAC GAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatACGGGGAACATTTCTGCAG AGAAAGGTGGCTCTATCATCTTACAATGTCACCTCTCCTCCACCACGGCACAAGTGACCCAG GTCAACTGGGAGCAGCAGGACCAGCTTCTGGCCATTTGTAATGCTGACTTGGGGTGGCACA TCTCCCCATCCTTCAAGGATCGAGTGGCCCCAGGTCCCGGCCTGGGCCTCACCCTCCAGTCG CTGACCGTGAACGATACAGGGGAGTACTTCTGCATCTATCACACCTACCCTGATGGGACGT ACACTGGGAGAATCTTCCTGGAGGTCCTAGAAAGCTCAGGTATTCCTGCTGGAGCAAGTTG GTGGATAAACCTCTCCCTCTAGCATAGAAAATGCAATCCTGAAACACTGCACAGCAGGGCT TCTCAATTCGGGATCACATTTGAATCACCTGAGGAGATTTTAAATCATACTGATGCCGAGGC C 1806 pARBI- 970: TIGIT_2_E ndogeno us_77 GAGGAGATGGGCTGGGCTGGGCTGGAGTAGAGATGTGTGGAGAAGGGTGAGAAGACTG GAAAGACAACCTGAATGGGGGACTGGGAGCCTTGAATAACAGGCATGGAGAGGAGCGTC TCTTGAAATGGAAGAAACAGGAAATAATTACAGCCTCTATGGAGGAGCAACAGGATGGAC TGGAGAAACTATCATTCCAAAATCCAGTTGGGGCCTCAAAGGCCCTTAGAATTTIICTAGGA AGGTTGAAGGCCAGCTGCTGACCCAGGACTCACATGTGCTTCGTCCTCTTCCCTAGGAATG ATGACAGGCACAATAGAAACAACGGGGAACAI 1 ILIGCAGAGAAAGGTGGCTCTATCATCT TACAATGTCACCTCTCCTCCACCACGGCACAAGTGACCCAGGTCAACTGGGAGCAGCAGGA CCAGCTTCTGGCCATTTGTAATGCTGACtccggatccggagagggcaggggatctctccttacttgtggcga 1806 WO 2022/093846 PCT/US2021/056689 cgtggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCC ATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGC GAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGC CCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTAC CCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGG AGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGA GGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAA CATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGAC AAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGC GTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGC CCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCG ATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCT GTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattt ttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTTGGGGTGGCACATCTCCCCATCCT TCAAGGATCGAGTGGCCCCAGGTCCCGGCCTGGGCCTCACCCTCCAGTCGCTGACCGTGAA CGATACAGGGGAGTACTTCTGCATCTATCACACCTACCCTGATGGGACGTACACTGGGAGA ATCTTCCTGGAGGTCCTAGAAAGCTCAGGTATTCCTGCTGGAGCAAGTTGGTGGATAAACC TCTCCCTCTAG CATAG AAAATG CAATCCTG AAACACTG CACAG C AG G G CTTCTCAATTCG G G ATCACATTTGAATCACCTGAGGAGATTTTAAATCATACTGATGCCGAGGCCTCACCCAGACC AATTCAATCAGAATCCCTAATAGCAGAGCTAAACAAGGGTAAGGTCTAAAAGCATTTCCAG GTGATTCTAATGGGCAGCCAATACTGAGAACCACTGTTCTTATGTAAGAAGCACATCpARBI- 971: TIGIT3E ndogeno us_78 CCTCCCTGTGGGCGAGGTGTAAAGAGGGGCAGAAGTCAGCTCTGGAAGCATAGGGCAGT GGGTGGGGAGGAGATGGGCTGGGCTGGGCTGGAGTAGAGATGTGTGGAGAAGGGTGAG AAGACTGGAAAGACAACCTGAATGGGGGACTGGGAGCCTTGAATAACAGGCATGGAGAG GAGCGTCTCTTGAAATGGAAGAAACAGGAAATAATTACAGCCTCTATGGAGGAGCAACAG GATGGACTGGAGAAACTATCATTCCAAAATCCAGTTGGGGCCTCAAAGGCCCTTAGAATTT TTCTAGGAAGGTTGAAGGCCAGCTGCTGACCCAGGACTCACATGTGCTTCGTCCTCTTCCCT AGGAATGATGACAGGCACAATAGAAACAACGGGGAACATTTCTGCAGAGAAAGGTGGCTC TATCATCTTACAATGTCACCTCTCCTCCACCtccggatccggagagggcaggggatctctccttacttgtggc gacgtggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCC CATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGG CGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTG CCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTA CCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAG GAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCG AGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCA ACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGA CAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAG CGTG CAG CTCG CCG ACCACTACCAG CAG AACACCCCCATCGGCG ACG GCCCCGTG CTGCTG CCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGC GATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGC TGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatt tttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatACGGCACAAGTGACCCAGGTCAAC TGGGAGCAGCAGGACCAGCTTCTGGCCATTTGTAATGCTGACTTGGGGTGGCACATCTCCC CATCCTTCAAGGATCGAGTGGCCCCAGGTCCCGGCCTGGGCCTCACCCTCCAGTCGCTGAC CGTGAACGATACAGGGGAGTACTTCTGCATCTATCACACCTACCCTGATGGGACGTACACT GGGAGAATCTTCCTGGAGGTCCTAGAAAGCTCAGGTATTCCTGCTGGAGCAAGTTGGTGG ATAAACCTCTCCCTCTAGCATAGAAAATGCAATCCTGAAACACTGCACAGCAGGGCTTCTCA ATTCGGGATCACATTTGAATCACCTGAGGAGATTTTAAATCATACTGATGCCGAGGCCTCAC CCAGACCAATTCAATCAGAATCCCTAATAGCAGAGCTAAACAAGGGTAAGGTCTAAAAG 1806 pARBI- 972: TRAC_1_ Endogeno us_79 TAATG CCCAG CCTAAGTTG G G G AG ACCACTCCAG ATTCCAAG ATGTACAGTTTG CTTTG CTG GGCCI 1 1 1 1 CCCATGCCTGCCTTTACTCTGCCAGAGTTATATTGCTGGGGTTTTGAAGAAGAT CCTATTAAATAAAAGAATAAGCAGTATTATTAAGTAGCCCTGCATTTCAGGTTTCCTTGAGT GGCAGGCCAGGCCTGGCCGTGAACGTTCACTGAAATCATGGCCTCTTGGCCAAGATTGATA GCTTGTGCCTGTCCCTGAGTCCCAGTCCATCACGAGCAGCTGGI 1 IUIAAGATGCTATTTCC 1806 WO 2022/093846 PCT/US2021/056689 CGTATAAAGCATGAGACCGTGACTTGCCAGCCCCACAGAGCCCCGCCCTTGTCCATCACTG GCATCTGGACTCCAGCCTGGGTTGGGGCAAAGAGGGAAATGAGATCATGTCCTAACCCTG ATCCTCTTGTCCCACAGATtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggaga accccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTC GAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGA TGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCT GGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCAC ATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCA TCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACA CCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGG GGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAA GAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCT CGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAAC CACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATG GTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatg attgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcat tctagttgtggtttgtccaaactcatcaatgtatcttatATCCAGAACCCTGACCCTGCCGTGTACCAGCTG AGAGACTCTAAATCCAGTGACAAGTCTGTCTGCCTATTCACCGATTTTGATTCTCAAACAAAT GTGTCACAAAGTAAGGATTCTGATGTGTATATCACAGACAAAACTGTGCTAGACATGAGGT CTATGGACTTCAAGAGCAACAGTGCTGTGGCCTGGAGCAACAAATCTGACTTTGCATGTGC AAACGCCTTCAACAACAGCATTATTCCAGAAGACACCTTCTTCCCCAGCCCAGGTAAGGGCA GCTTTGGTGCCTTCGCAGGCTGTTTCCTTGCTTCAGGAATGGCCAGGTTCTGCCCAGAGCTC TGGTCAATGATGTCTAAAACTCCTCTGATTGGTGGTCTCGGCCTTATCCATTGCCACCAAAA CCCTCI 1 1 1 IACTAAGAAACAGTGAGCCTTGTTCTGGCAGTCCAGApARBI- 973: TRAC_2_ Endogeno us_80 GATTCCAAGATGTACAG 1 1 IGCITTGCTGGGCCI 1 1 1 1 CCCATGCCTGCC1 1 IACTCTGCCAG AGTTATATTGCTGGGGTTTTGAAGAAGATCCTATTAAATAAAAGAATAAGCAGTATTATTAA GTAGCCCTGCATTTCAGGTTTCCTTGAGTGGCAGGCCAGGCCTGGCCGTGAACGTTCACTG AAATCATGGCCTCTTGGCCAAGATTGATAGCTTGTGCCTGTCCCTGAGTCCCAGTCCATCAC GAGCAGCTGGTTTCTAAGATGCTATTTCCCGTATAAAGCATGAGACCGTGACTTGCCAGCCC CACAGAGCCCCGCCCTTGTCCATCACTGGCATCTGGACTCCAGCCTGGGTTGGGGCAAAGA GGGAAATGAGATCATGTCCTAACCCTGATCCTCTTGTCCCACAGATATCCAGAACCCTGACC CTGCCGTGTACCAGCTGtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggagaac cccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGA GCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATG CCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTG GCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACA TGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCAT CTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACAC CCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGG GCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAG AACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTC GCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACC ACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGT CCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgat tgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattc tagttgtggtttgtccaaactcatcaatgtatcttatAGAGACTCTAAATCCAGTGACAAGTCTGTCTGCCT ATTCACCGATTTTGATTCTCAAACAAATGTGTCACAAAGTAAGGATTCTGATGTGTATATCA CAGACAAAACTGTGCTAGACATGAGGTCTATGGACTTCAAGAGCAACAGTGCTGTGGCCTG GAGCAACAAATCTGACTTTGCATGTGCAAACGCCTTCAACAACAGCATTATTCCAGAAGACA CCTTCTTCCCCAG CCCAG GTAAG G G GAG CTTTG GTG CCTTCG C AG G CTGTTTCCTTG CTTCA GGAATGGCCAGGTTCTGCCCAGAGCTCTGGTCAATGATGTCTAAAACTCCTCTGATTGGTG GTCTCGGCCTTATCCATTGCCACCAAAACCCTCI 1 1 1 1ACTAAGAAACAGTGAGCCTTGTTCT GGCAGTCCAGAGAATGACACGGGAAAAAAGCAGATGAAGAGAAG 1806 pARBI- 974:TTCCTGTGGTAGCGGAACTCACTAAGGGGCCCATCTGGACCCGAGGTATTGTGATGATAAA TTCTGAGCACCTACCCCATCCCCAGAAGGGCTCAGAAATAAAATAAGAGCCAAGTCTAGTC1806 WO 2022/093846 PCT/US2021/056689 TRAC_3_ Endogeno us_81 GGTGTTTCCTGTCTTGAAACACAATACTGTTGGCCCTGGAAGAATGCACAGAATCTGTTTGT AAGGGGATATGCACAGAAGCTGCAAGGGACAGGAGGTGCAGGAGCTGCAGGCCTCCCCC ACCCAGCCTGCTCTGCCTTGGGGAAAACCGTGGGTGTGTCCTGCAGGCCATGCAGGCCTGG GACATGCAAGCCCATAACCGCTGTGGCCTCTTGGTTTTACAGATACGAACCTAAACTTTCAA AACCTGTCAGTGATTGGGTTCCGAATCCTCCTCCTGAAAGTGGCCGGGTTTAATCTGCTCAT GACGCTGCGGCTGTGGTCCAGCtccggatccggagagggcaggggatctctccttacttgtggcgacgtgga ggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCT GGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGG GCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGT GCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCG ACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCG CACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGC GACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATC CTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGC AGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGC AGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGA CAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCAC ATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACA Aatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcact gcattctagttgtggtttgtccaaactcatcaatgtatcttatTGAGGTGAGGGGCCTTGAAGCTGGGAGTG GGGTTTAGGGACGCGGGTCTCTGGGTGCATCCTAAGCTCTGAGAGCAAACCTCCCTGCAGG GTCTTGCTTTTAAGTCCAAAGCCTGAGCCCACCAAACTCTCCTACTTCTTCCTGTTACAAATT CCTCTTGTGCAATAATAATGGCCTGAAACGCTGTAAAATATCCTCATTTCAGCCGCCTCAGTT GCACTTCTCCCCTATGAGGTAGGAAGAACAGTTGTTTAGAAACGAAGAAACTGAGGCCCCA CAGCTAATGAGTGGAGGAAGAGAGACACTTGTGTACACCACATGCCTTGTGTTGTACTTCT CTCACCGTGTAACCTCCTCATGTCCTCTCTCCCCAGTACGGCTCTCTTAGCTCAGTAGAAAGA AGACATTACACTCATATTACACCCCAATCCTGGCTAGAGTCTCCGCACCpARBI- 975: TRAC_4_ Endogeno us_82 ATTATTAAGTAGCCCTGCATTTCAGGTTTCCTTGAGTGGCAGGCCAGGCCTGGCCGTGAAC GTTCACTGAAATCATGGCCTCTTGGCCAAGATTGATAGCTTGTGCCTGTCCCTGAGTCCCAG TCCATCACGAGCAGCTGG1 1 ILIAAGATGCTATTTCCCGTATAAAGCATGAGACCGTGACTT GCCAGCCCCACAGAGCCCCGCCCTTGTCCATCACTGGCATCTGGACTCCAGCCTGGGTTGG GGCAAAGAGGGAAATGAGATCATGTCCTAACCCTGATCCTCTTGTCCCACAGATATCCAGA ACCCTGACCCTGCCGTGTACCAGCTGAGAGACTCTAAATCCAGTGACAAGTCTGTCTGCCTA TTCACCGATTTTGATTCTCAAACAAATGTGTCACAAAGTAAGGATTCTGATGTGTATATCAC AGACAAAACTGTGCTAGACtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggag aaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTC GAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGA TGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCT GGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCAC ATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCA TCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACA CCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGG GGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAA GAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCT CGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAAC CACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATG GTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatg attgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcat tctagttgtggtttgtccaaactcatcaatgtatcttatATGAGGTCTATGGACTTCAAGAGCAACAGTGCT GTGGCCTGGAGCAACAAATCTGACTTTGCATGTGCAAACGCCTTCAACAACAGCATTATTCC AGAAGACACCTTCTTCCCCAGCCCAGGTAAGGGCAGCTTTGGTGCCTTCGCAGGCTGTTTCC TTG CTTCAG G A ATG G CCAG GTTCTG CCCAG AG CTCTG GTCAATG ATGTCTAAAACTCCTCTG ATTGGTGGTCTCGGCCTTATCCATTGCCACCAAAACCCTCI 1 1 1 1ACTAAGAAACAGTGAGC CTTGTTCTGGCAGTCCAGAGAATGACACGGGAAAAAAGCAGATGAAGAGAAGGTGGCAG 1806 WO 2022/093846 PCT/US2021/056689 G AG AG G G CACGTG G CCCAG CCTCAGTCTCTCC AACTG AGTTCCTG CCTG CCTG CCTTTG CTC AGACTGTTTGCCCCTTACTGCTCTTCTAGGCCTCATTCTAAGCCCCTTpARBI- 976: TRAC_6_ Endogeno us_84 TTCATTTCCATTTGAGTTGTTCTTATTGAGTCATCCTTCCTGTGGTAGCGGAACTCACTAAGG GGCCCATCTGGACCCGAGGTATTGTGATGATAAATTCTGAGCACCTACCCCATCCCCAGAA GGGCTCAGAAATAAAATAAGAGCCAAGTCTAGTCGGTGTTTCCTGTCTTGAAACACAATAC TGTTGGCCCTGGAAGAATGCACAGAATCTGTTTGTAAGGGGATATGCACAGAAGCTGCAA GGGACAGGAGGTGCAGGAGCTGCAGGCCTCCCCCACCCAGCCTGCTCTGCCTTGGGGAAA ACCGTGGGTGTGTCCTGCAGGCCATGCAGGCCTGGGACATGCAAGCCCATAACCGCTGTG GCCTCTTGGTTTTACAGATACGAACCTAAACTTTCAAAACCTGTCAGTGATTGGGTTCCGAA TCCTCCTCCTGAAAGTGGCCGGGtccggatccggagagggcaggggatctctccttacttgtggcgacgtgga ggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCT GGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGG GCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGT GCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCG ACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCG CACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGC GACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATC CTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGC AGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGC AGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGA CAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCAC ATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACA Aatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcact gcattctagttgtggtttgtccaaactcatcaatgtatcttatTTTAATCTGCTCATGACGCTGCGGCTGTGG TCCAGCTGAGGTGAGGGGCCTTGAAGCTGGGAGTGGGGTTTAGGGACGCGGGTCTCTGG GTGCATCCTAAGCTCTGAGAGCAAACCTCCCTGCAGGGTCTTGCTTTTAAGTCCAAAGCCTG AGCCCACCAAACTCTCCTACTTCTTCCTGTTACAAATTCCTCTTGTGCAATAATAATGGCCTG AAACGCTGTAAAATATCCTCATTTCAGCCGCCTCAGTTGCACTTCTCCCCTATGAGGTAGGA AGAACAGTTGTTTAGAAACGAAGAAACTGAGGCCCCACAGCTAATGAGTGGAGGAAGAGA GACACTTGTGTACACCACATGCCTTGTGTTGTACTTCTCTCACCGTGTAACCTCCTCATGTCC TCTCTCCCCAGTACGGCTCTCTTAGCTCAGTAGAAAGAAGACATTACACTC 1806 pARBI- 977: TRACEn dogenous CAGTCCATCACGAGCAGCTGGTTTCTAAGATGCTATTTCCCGTATAAAGCATGAGACCGTGA CTTGCCAGCCCCACAGAGCCCCGCCCTTGTCCATCACTGGCATCTGGACTCCAGCCTGGGTT GGGGCAAAGAGGGAAATGAGATCATGTCCTAACCCTGATCCTCTTGTCCCACAGATATCCA GAACCCTGACCCTGCCGTGTACCAGCTGAGAGACTCTAAATCCAGTGACAAGTCTGTCTGC CTATTCACCGATTTTGATTCTCAAACAAATGTGTCACAAAGTAAGGATTCTGATGTGTATATC ACAGACAAAACTGTGCTAGACATGAGGTCTATGGACTTCAAGAGCAACAGTGCTGTGGCCT GGAGCAACAAATCTGACTTTGCATGTGCAAACGCCTTCAACAACAGCATTATTCCAGAAGA CACCTTCTTCCCCAGCCCAtccggatccggagagggcaggggatctctccttacttgtggcgacgtggaggaga accccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTC GAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGA TGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCT GGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCAC ATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCA TCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACA CCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGG GGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAA GAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCT CGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATG GTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatg attgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcat tctagttgtggtttgtccaaactcatcaatgtatcttatGGTAAGGGCAGCTTTGGTGCCTTCGCAGGCTGT TTCCTTGCTTCAGGAATGGCCAGGTTCTGCCCAGAGCTCTGGTCAATGATGTCTAAAACTCC TCTGATTGGTGGTCTCGGCCTTATCCATTGCCACCAAAACCCTCI 1 1 1 1ACTAAGAAACAGTG 1806 100 WO 2022/093846 PCT/US2021/056689 AGCCTTGTTCTGGCAGTCCAGAGAATGACACGGGAAAAAAGCAGATGAAGAGAAGGTGGC AGGAGAGGGCACGTGGCCCAGCCTCAGTCTCTCCAACTGAGTTCCTGCCTGCCTGCCTTTGC TCAGACTGTTTGCCCCTTACTGCTCTTCTAGGCCTCATTCTAAGCCCCTTCTCCAAGTTGCCTC TCCTTATTTCTCCCTGTCTG CC AAAAAATCTTTCCC AG CTCACTA AGTCAGTCTCACG C AGTC ACTCATTAACCCACCAATCACTGATTGTGCCGGCACATGAATGpARBI- 978: TRIM28_ lEndoge nous_85 TGAGGAAGAAGCGCGGGCGGCGCCTTCGGGAGGCGAGCAGGCAGCAGTTGGCCGTGCCG TAGCAGCGTCCCGCGCGCGGCGGGCAGCGGCCCAGGAGGCGCGTGGCGGCGCTCGGCCT CGCGGCGGCGGCGGCGGCAGCGGCCCAGCAGTTGGCGGCGAGCGCGTCTGCGCCTGCGC GGCGGGCCCCGCGCCCCTCCTCCCCCCCTGGGCGCCCCCGGCGGCGTGTGAATGGCGGCCT CCGCGGCGGCAGCCTCGGCAGCAGCGGCCTCGGCCGCCTCTGGCAGCCCGGGCCCGGGCG AGGGCTCCGCTGGCGGCGAAAAGCGCTCCACCGCCCCTTCGGCCGCAGCCTCGGCCTCTGC CTCAGCCGCGGCGTCGTCGCCCGCGGGGGGCGGCGCCGAGGCGCTGGAGCTGCTGGAGC ACTGCGGCGTGTGCAGAGAGCGCCTGCGACCCtccggatccggagagggcaggggatctctccttactt gtggcgacgtggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGG TGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCG AGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCA AGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGC CGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACG TCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAA GTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATG GCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGAC GGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGC TGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAA GCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGAC GAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGAGAGGGAGCCCCGCCTGC TGCCCTGTTTGCACTCGGCCTGTAGTGCCTGCTTAGGGCCCGCGGCCCCCGCCGCCGCCAAC AGCTCGGGGGACGGCGGGGCGGCGGGCGACGGCACCGGTAAGTACGAAGTGATCGGTGC CACCCCTCCCCCTACTCTCTGCCTTTGATTCCGACTGGGTGCAGAGATGAGGATGCCACCTG GGCGAGAGGATGGGGGCCCGGACAGGGCACGGGAAATACI 1 ILIGGGTCCTGCATACGA ACGTGGGTTTGTGCTGGCCGCTGAGATGGGACATCTGACTAAAGTTGGAGAAAAGAAGGC TCGGGGAGGGGAGGGGCTGGTTCGCTGCGGGATAATGGTCGGGGGCCCACCCAGCAGGG GAATGGTGGGGGCCATAACCTGGGTGGGAACTTGTAACAGTCTCCCACATCCCTGCTTCTC GAAGTGGTG 1806 pARBI- 979: TRIM28_ 2_Endoge nous_86 TCGAAGTGGTGGACTGTCCCGTGTGCAAGCAACAGTGCTTCTCCAAAGACATCGTGGAGAA TTATTTCATGCGTGATAGTGGCAGCAAGGCTGCCACCGACGCCCAGGATGCGAACCAGGTG CGTCCTATCTCAGCAACCACAAGGAGGI 1 ILIGGGGAGGGGGCATCTGCGCAGGAGGAGC TTG G CACCAG CTCCAG G CTGTTACTCCACTTTCCCAAG G CTCTG G GTG G G CTG CCTAG GTTG GGTCAAGGGACCAATCTTAAATCTCCGGTTGTATITICTGGGATGTAAACGTGGATCTATCA AGTTGTCTTGCCTTCTCTGACCCTGCCTTTGTCTGGCAGTGCTGCACTAGCTGTGAGGATAA TGCCCCAGCCACCAGCTACTGTGTGGAGTGCTCGGAGCCTCTGTGTGAGACCTGTGTAGAG GCGCACCAGCGGGTGAAGTACtccggatccggagagggcaggggatctctccttacttgtggcgacgtggag gagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTG GTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGG CGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTG CCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGA CCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGC ACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGC GACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATC CTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGC AGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGC AGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGA CAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCAC ATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACA 1806 101 WO 2022/093846 PCT/US2021/056689 Ad IgdllgllldllgLdgLlldlddlgglldLdddldddgLddldgLdlLdLdddlllLdLdddldddgLdlllllllLdLl gcattctagttgtggtttgtccaaactcatcaatgtatcttatACCAAGGACCATACTGTGCGCTCTACTGGT ACATGAGGCTGAGGGGGGCTGTTGGAGTTGTTCTCCCATGTGTGCCCTCAGTTGCTTTTATG ATGTTGGTTGCATCTGGTGGATGGGTCCTAGAGTTCTCTAGGGGGTGCCGCCCGAAGGGCC CGAGGGCAGAACTCCAGAAGCAGAAAAACTGGGGTTGTGGTGTGTAGTCTCTAGGGCCTA GGTGGGAGAGGGTGGGAAGGGGAAATAAGGGAGACCTTAATGTGCTGCAGGGAGGTAC AAAGGGTTTGAGAAGGCTTATCAGGGAGTTGTCAGACCTGGTGGTGAAGGGCTCAGCATA TGCAAACAGGGAAAGGCATGGTGTGAAGGGCI 1 ILIGGGTTTGTGGTTCCCTGGCACACAT CTGGTATAAGATGCTGCTAGGGAAAGTAGACTGTGGGTCCATGGATTATAAGTGATGApARBI- 980: TRIM28_ 3_Endoge nous_87 GGCGCCCAATGCGCGTGCGCGGCGGCGTCGGCGCCAGTTAI 1 ILIGICCCGCCCCCCGGCC TCGGCTCI 1 ILIGCGAGCGGGCGCGCGGGCGAGCGGTTGTGCTTGTGCTTGTGGCGCGTG GTGCGGGTTTCGGCGGCGGCTGAGGAAGAAGCGCGGGCGGCGCCTTCGGGAGGCGAGCA GGCAGCAGTTGGCCGTGCCGTAGCAGCGTCCCGCGCGCGGCGGGCAGCGGCCCAGGAGG CGCGTGGCGGCGCTCGGCCTCGCGGCGGCGGCGGCGGCAGCGGCCCAGCAGTTGGCGGC GAGCGCGTCTGCGCCTGCGCGGCGGGCCCCGCGCCCCTCCTCCCCCCCTGGGCGCCCCCGG CGGCGTGTGAATGGCGGCCTCCGCGGCGGCAGCCTCGGCAGCAGCGGCCTCGGCCGCCTC TGGCAGCCCGGGCCCGGGCGAGGGCTCCGCTtccggatccggagagggcaggggatctctccttacttgt ggcgacgtggaggagaaccccggccccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGT GCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGA GGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAA GCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCC GCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGT CCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAA GTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATG GCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGAC GGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGC TGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAA GCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGAC GAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGGCGGCGAAAAGCGCTCCA CCGCCCCTTCGGCCGCAGCCTCGGCCTCTGCCTCAGCCGCGGCGTCGTCGCCCGCGGGGGG CGGCGCCGAGGCGCTGGAGCTGCTGGAGCACTGCGGCGTGTGCAGAGAGCGCCTGCGAC CCGAGAGGGAGCCCCGCCTGCTGCCCTGTTTGCACTCGGCCTGTAGTGCCTGCTTAGGGCC CGCGGCCCCCGCCGCCGCCAACAGCTCGGGGGACGGCGGGGCGGCGGGCGACGGCACCG GTAAGTACGAAGTGATCGGTGCCACCCCTCCCCCTACTCTCTGCCTTTGATTCCGACTGGGT GCAGAGATGAGGATGCCACCTGGGCGAGAGGATGGGGGCCCGGACAGGGCACGGGAAA TACI 1 ILIGGGTCCTGCATACGAACGTGGGTTTGTGCTGGCCGCTGAGATGGGACATCTGA CTAAAGTTGG 1806 pARBI- 596:APRT_1_E xogenous _1 ATCTCGGCCAATAAAGGAGAAAGGGCGCGGCCCGTACGCGCGCCAGGTGCGTGGGCGAG ACCAGCTCACGCCCCTCCTCCAGCCGCCAAGGCCCCGGCCCACAGCTGCCTGGCTGCAGTC AGAAGCGTAGCCCGAGACAAGGAAGGGCGCCTTGACTCGCACTTTTGTCCGGTTCGAACGT TCTGctcagtggtgcgtggaatgcgagcgcgtcttaaaatcgatggcgcctaggagtccatgaaatacggTACAGG CTTCCGGCGACGGATGCCCCGCCCCTCACCCACGCTCCGCCCTCCGGGGATGCCCCACCCCT CGTGGCGGTCCCGCCCGTCCCCGCGCAGGCGCGCTCGGGCTGCCGCTGGCTCTTCGCACGC GGCCATGGCCGACTCCGAGCTGCAGCTGGTTGAGCAGCGGATCCGCAGCTTCCCCGACTTC CCCACCCCAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaa ggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggg gtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctatg gGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCG AGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGGT AAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACC GTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCAGAACAC AGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCG CCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGT 2541 102 WO 2022/093846 PCT/US2021/056689 CCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTG GAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGT CTTTGTTTCGTTIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGA GCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCC ATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGC GAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGC CCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTAC CCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGG AGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGA GGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAA CATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGAC AAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGC GTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGC CCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCG ATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCT GTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattt ttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGGCGTGGTATTCAGGTGCACGCAC AGGCCGCCCTCGTGGCGCCCCGACCTGCGGGCCTACGGATGGGAGCGCGTGGCCCGCGAC CTCCGGGCGGGCGGGGCGGGAACCCTCGTCTTTCGCCCCCGGGGCCCTGCCCTCCTTCGGC CCCGGCGTCACCAGGCCTGTCCTTGGGTCCAGGGACATCTCGCCCGTCCTGAAGGACCCCG CCTCCTTCCGCGCCGCCATCGGCCTCCTGGCGCGACACCTGAAGGCGACCCACGGGGGCCG CATCG ACTACATCG C AG G CG AGTG CCCAGTG G CCG CATCTAG G G CG CTTCCG CCTCTG CG C GCGCCGAGGGCAGCACGTGGGCTCTGCGCGTCTGCTTGGGGGAGGGCCTTTGGGGTGCTT CAGGGGGCGCCGGGACGGGCGCCGTGCTTGGGTCGCCCGGGAAGGGTTGTGAGATTGAG CCCpARBI- 597: APRT2E xogenous _2 TGCCCCGCCCCTCACCCACGCTCCGCCCTCCGGGGATGCCCCACCCCTCGTGGCGGTCCCGC CCGTCCCCGCGCAGGCGCGCTCGGGCTGCCGCTGGCTCTTCGCACGCGGCCATGGCCGACT CCGAGCTGCAGCTGGTTGAGCAGCGGATCCGCAGCTTCCCCGACTTCCCCACCCCAGGCGT GGTATTCAGGTGCACGCACAGGCCGCCCTCGTGGCGCCCCGACCTGCGGGCCTACGGATG GGAGCGCGTGGCCCGCGACCTCCGGGCGGGCGGGGCGGGAACCCTCGTCTTTCGCCCCCG GGGCCCTGCCCTCCTTCGGCCCCGGCGTCACCAGGCCTGTCCTTGGGTCCAGGGACATCTC GCCCGTCCTGAAGGACCCCGCCTCCTTCCGCGCCGCCATCGGCCTCCTGGCGCGACACCTG AAGGCGACCCACGGGGGCCGCATCtgacgactgtgccttctagttgccagccatctgttgtttgcccctccccc gtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagta ggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctg gggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACA TCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAG AAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAG GGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGGGT TTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCG CCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTG CCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGT CCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCT TGCTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACC GGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTC ACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGC GTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGC ACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGC AGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCC GAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCG CCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACT TCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACG TCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAA CATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGA CGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGAC 2541 103 WO 2022/093846 PCT/US2021/056689 CCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTC TCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcaca aatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGACTACATC GCAGGCGAGTGCCCAGTGGCCGCATCTAGGGCGCTTCCGCCTCTGCGCGCGCCGAGGGCA GCACGTGGGCTCTGCGCGTCTGCTTGGGGGAGGGCCTTTGGGGTGCTTCAGGGGGCGCCG GGACGGGCGCCGTGCTTGGGTCGCCCGGGAAGGGTTGTGAGATTGAGCCCCCGAGGCCG CCGCGCTGTGCAGGCGTCCTTCCCGCAGGTTCCGGGTCCCCAGCCCAGGACAGGCGTGACC GAGTTGCCGGGTCAGTTGGTCTCCCTGGAGTGCCCAAGCTGAATCCACAGGGCCCAGCTGC CTTG CTTCTTGTTCCTTCTG CG AG CTG GTATTG AG CG CCTG CCACG AG CCAG G CCTTCCCTG GTGAAGATCACGGAATGCCCACCCAGGGAAGGGAGGCCTGGAGGCCTCCGGGAGAGCCC AAGAGGTGGCCCAGGGAGApARBI- 598: APRT3Exogenous _3 CGTTCTGctcagtggtgcgtggaatgcgagcgcgtcttaaaatcgatggcgcctaggagtccatgaaatacggTAC AGGCTTCCGGCGACGGATGCCCCGCCCCTCACCCACGCTCCGCCCTCCGGGGATGCCCCAC CCCTCGTGGCGGTCCCGCCCGTCCCCGCGCAGGCGCGCTCGGGCTGCCGCTGGCTCTTCGC ACGCGGCCATGGCCGACTCCGAGCTGCAGCTGGTTGAGCAGCGGATCCGCAGCTTCCCCG ACTTCCCCACCCCAGGCGTGGTATTCAGGTGCACGCACAGGCCGCCCTCGTGGCGCCCCGA CCTGCGGGCCTACGGATGGGAGCGCGTGGCCCGCGACCTCCGGGCGGGCGGGGCGGGAA CCCTCGTCTTTCGCCCCCGGGGCCCTGCCCTCCTTCGGCCCCGGCGTCACCAGGCCTGTCCTT GGGTCCAGGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctgga aggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctgggg ggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctat ggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCC GAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGG TAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACC GTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGCCGCCAGAACAC AGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCG CCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGT CCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTG GAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGT CTTTGTTTCGTTIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGA GCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCC ATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGC GAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGC CCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTAC CCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGG AGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGA GGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAA CATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGAC AAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGC GTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGC CCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCG ATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCT GTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattt ttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGACATCTCGCCCGTCCTGAAGGACC CCGCCTCCTTCCGCGCCGCCATCGGCCTCCTGGCGCGACACCTGAAGGCGACCCACGGGGG CCGCATCGACTACATCGCAGGCGAGTGCCCAGTGGCCGCATCTAGGGCGCTTCCGCCTCTG CGCGCGCCGAGGGCAGCACGTGGGCTCTGCGCGTCTGCTTGGGGGAGGGCCTTTGGGGTG CTTCAGGGGGCGCCGGGACGGGCGCCGTGCTTGGGTCGCCCGGGAAGGGTTGTGAGATT GAGCCCCCGAGGCCGCCGCGCTGTGCAGGCGTCCTTCCCGCAGGTTCCGGGTCCCCAGCCC AGGACAGGCGTGACCGAGTTGCCGGGTCAGTTGGTCTCCCTGGAGTGCCCAAGCTGAATC CACAGGGCCCAGCTGCCTTGCTTCTTGTTCCTTCTGCGAGCTGGTATTGAGCGCCTGCCACG A 2541 pARBI- 599: B2M_1_E AGTAATTTGATGGGGGCTATTATGAACTGAGAAATGAACTTTGAAAAGTATCTTGGGGCCA AATCATGTAGACTCTTGAGTGATGTGTTAAGGAATGCTATGAGTGCTGAGAGGGCATCAGA AGTCCTTGAGAGCCTCCAGAGAAAGGCTCTTAAAAATGCAGCGCAATCTCCAGTGACAGAA 2541 104 WO 2022/093846 PCT/US2021/056689 xogenous _4GATACTGCTAGAAATCTGCTAGAAAAAAAACAAAAAAGGCATGTATAGAGGAATTATGAG GGAAAGATACCAAGTCACGGTTTATTCTTCAAAATGGAGGTGGCTTGTTGGGAAGGTGGA AGCTCATTTGGCCAGAGTGGAAATGGAATTGGGAGAAATCGATGACCAAATGTAAACACTT GGTGCCTGATATAGCTTGACACCAAGTTAGCCCCAAGTGAAATACCCTGGCAATATTAATGT GTCTTTTCCCGATATTCCTCAGGTtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgt gccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtag gtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgg ggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACAT CGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGA AGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAG GGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGGGT TTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCG CCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTG CCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGT CCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCT TGCTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACC GGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTC ACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGC GTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGC ACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGC AGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCC GAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCG CCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACT TCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACG TCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAA CATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGA CGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGAC CCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTC TCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcaca aatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatACTCCAAAG ATTCAGGTTTACTCACGTCATCCAGCAGAGAATGGAAAGTCAAATTTCCTGAATTGCTATGT GTCTGGGTTTCATCCATCCGACATTGAAGTTGACTTACTGAAGAATGGAGAGAGAATTGAA AAAGTGGAGCATTCAGACTTGTCTTTCAGCAAGGACTGGTCTTTCTATCTCTTGTACTACACT GAATTCACCCCCACTGAAAAAGATGAGTATGCCTGCCGTGTGAACCATGTGACTTTGTCACA GCCCAAGATAGTTAAGTGGGGTAAGTCTTACATTCTTTTGTAAGCTGCTGAAAGTTGTGTAT GAGTAGTCATATCATAAAGCTGCTTTGATATAAAAAAGGTCTATGGCCATACTACCCTGAAT GAGTCCCATCCCATCTGATATAAACAATCTGCATATTGGGATTGTCAGGGAATGTTCTTAAA GATCAGApARBI- 600:B2M_2_E xogenous _5 AAGATCTTAATCTTCTGGGTTTCCGTTTTCTCGAATGAAAAATGCAGGTCCGAGCAGTTAAC TG G CTG G G G CACCATTAG C AAGTCACTTAG CATCTCTG G G G CC AGTCTG CAAAG CG AG G G GGCAGCCTTAATGTGCCTCCAGCCTGAAGTCCTAGAATGAGCGCCCGGTGTCCCAAGCTGG GGCGCGCACCCCAGATCGGAGGGCGCCGATGTACAGACAGCAAACTCACCCAGTCTAGTG CATGCCTTCTTAAACATCACGAGACTCTAAGAAAAGGAAACTGAAAACGGGAAAGTCCCTC TCTCTAACCTGGCACTGCGTCGCTGGCTTGGAGACAGGTGACGGTCCCTGCGGGCCTTGTC CTGATTGGCTGGGCACGCGTTTAATATAAGTGGAGGCGTCGCGCTGGCGGGCATTCCTGAA GCTGACAGCATTCGGGCCGAGATGtgacgactgtgccttctagttgccagccatctgttgtttgcccctccccc gtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagta ggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctg gggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACA TCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAG AAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAG GGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGGGT TTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCG CCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTG CCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGT 2541 105 WO 2022/093846 PCT/US2021/056689 CCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCT TGCTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACC GGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTC ACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGC GTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGC ACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGC AGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCC GAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCG CCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACT TCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACG TCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAA CATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGA CGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGAC CCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTC TCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcaca aatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTCTCGCTCC GTGGCCTTAGCTGTGCTCGCGCTACTCTCTCI 1 ILIGGCCTGGAGGCTATCCAGCGTGAGTC TCTCCTACCCTCCCGCTCTGGTCCTTCCTCTCCCGCTCTGCACCCTCTGTGGCCCTCGCTGTGC TCTCTCGCTCCGTGACTTCCCTTCTCCAAGTTCTCCTTGGTGGCCCGCCGTGGGGCTAGTCCA GGGCTGGATCTCGGGGAAGCGGCGGGGTGGCCTGGGAGTGGGGAAGGGGGTGCGCACC CGGGACGCGCGCTACTTGCCCCTTTCGGCGGGGAGCAGGGGAGACCTTTGGCCTACGGCG ACGGGAGGGTCGGGACAAAGTTTAGGGCGTCGATAAGCGTCAGAGCGCCGAGGTTGGGG GAGGGI 1 ILICTTCCGCTCTTTCGCGGGGCCTCTGGCTCCCCCAGCGCAGCTGGAGTGGGG GACGGGTAGGCTCGpARBI- 601:B2M_3_E xogenous _6 AGGAATGCTATGAGTGCTGAGAGGGCATCAGAAGTCCTTGAGAGCCTCCAGAGAAAGGCT CTTAAAAATGCAGCGCAATCTCCAGTGACAGAAGATACTGCTAGAAATCTGCTAGAAAAAA AACAAAAAAGGCATGTATAGAGGAATTATGAGGGAAAGATACCAAGTCACGGTTTATTCTT CAAAATGGAGGTGGCTTGTTGGGAAGGTGGAAGCTCATTTGGCCAGAGTGGAAATGGAAT TGGGAGAAATCGATGACCAAATGTAAACACTTGGTGCCTGATATAGCTTGACACCAAGTTA GCCCCAAGTGAAATACCCTGGCAATATTAATGTGTCTTTTCCCGATATTCCTCAGGTACTCCA AAGATTCAGGTTTACTCACGTCATCCAGCAGAGAATGGAAAGTCAAATTTCCTGAATTGCTA TGTGTCTGGGTTTCATCCATCCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgc cttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtg tcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgggga tgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGG TGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTG GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGC CGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCT ACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTC CTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCG GCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGC TCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGC GCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA AG G AG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG 2541 106 WO 2022/093846 PCT/US2021/056689 GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGACATTGAAGTT GACTTACTGAAGAATGGAGAGAGAATTGAAAAAGTGGAGCATTCAGACTTGTCTTTCAGCA AGGACTGGTCTTTCTATCTCTTGTACTACACTGAATTCACCCCCACTGAAAAAGATGAGTAT GCCTGCCGTGTGAACCATGTGACTTTGTCACAGCCCAAGATAGTTAAGTGGGGTAAGTCTT ACATTCTTTTGTAAGCTGCTGAAAGTTGTGTATGAGTAGTCATATCATAAAGCTGCTTTGAT ATAAAAAAGGTCTATGGCCATACTACCCTGAATGAGTCCCATCCCATCTGATATAAACAATC TGCATATTGGGATTGTCAGGGAATGTTCTTAAAGATCAGATTAGTGGCACCTGCTGAGATA CTGATGCACAGCATGG1 1 IUIGAACCAGTAGTTTCCCTGCAGTTGAGCAGGGAGCAGCAGC AGCACTTGpARBI- 602: CAPNS1_ l_Exogen ous_7 GATCTCACATTCTAGCGCCCAGACATGTCGGGAACGCCTTACGCCAACTTGGGGTCCCCACC AAGAGAACCCCCACCAGATCTGCACCCTCCCCTTCACGCGTGCACCCAGTCCAGGCTCCCTC AAGCCCCACGGGTGCCTTTTAGACCTGAGGAGGTTGCAAACCTGATCCCCCATACCTGCCCC ACCCATCCGCGGACAACCCGCCCTCGCAAACTCAGACCCCCACCCGGAGGCTTCAGATTCCT CCCAGGTCCAGCTGCCGGAAATGCGTGTTTGAAGGGAGGGTGTGGGCTCAGGGGCGAAG CACCCACTGGTCCCCTTTTTTCCCCCCAGCAGTGAGTCGCAGCCATGTTCCTGGTTAACTCGT TCTTGAAGGGCGGCGGCGGCGGCGGCGGGGGAGGCGGGGGCCTGGGTGGGGGCCTGGG AAATGTGCTTGGAGGCCTGATCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtg ccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggt gtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgggg atgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCG CCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAG GTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGT GGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTG CCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCC TACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCT CCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCC GGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTG CTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGG CGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA AG G AG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatAGCGGGGCCGG GGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGTGGTGGAGGCGGCGGTGGCGGTGG AACGGCCATGCGCATCCTAGGCGGAGTCATCAGCGCCATCAGGTAAGGCGGAGACTATCA GAGGGGCGGGGCCTGGGAATGGGAGGAGCCTCAGTGAGGCGTGGTCTGGGAGGGGCGT GGTCTAAAAATAGAATAGGATTAACCTGGAGGCTAACCTGGGTACATGAATTAGGCCGGG GAGGCCTGGTTTGAGAGTTCTGCTGTAAGGGGGTGGACCCCAGTGAGGCGGATATCAGTC ATTGGGGGCGGTGCTTGATATGGGAGTAGTCTGATTGTGTGGGACCAGGACAATGTGGTC CTGAGGGGACTGATGTGGAGTTTTGGCGGGTGGGGCTTATGGGTCTGGGCTCAGCCTGCA TTGGCTAACCTGGAGATGAACGTT 2541 pARBI- 603: CAPNS1_ CGGGCATTTAGGAAGCGGGCCATGGAGTAGGGTCTTGGGCAGATGGCACCTGAGGAGGA TAAGGCCTTGGGAAGCTGGGGCAGAGCCTCTATGAAGTGAGCCCTCCAAGGGGCGGGGTC TTTTGATTCTACGTGGGATTTTTTAGGTTTAGGGTGGCCAAGATGACTGAAATCTGCCACTG GGTAGGTGTGCCTGGCAGGAGGGGAGCCTCCCAGGGGACCGGTCTCTGGGTTTCCTCGAG 2541 107 WO 2022/093846 PCT/US2021/056689 2_Exogen ous_8GGTGGGGTTGGCCTGAGGAAGGGAGAAGAGGGGCACGACCAGGGCAGTGTGGATTGGG ACAGATGAGGACAAGAACAAATGAAAGGCACAGCAACCAAGTAAGGAAGATAACGGCTG GGGTCTGGAGCGTTGGGGCTGATGGTTCTGTAGTGCTGCCCGTTGGAGGCCCCGCCCCTG GCACTAACCCCTCCCCCTTATCTCTTCGCAGCtgacgactgtgccttctagttgccagccatctgttgtttgcc cctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattg tctgagtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcag gcatgctggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAG CGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCC TAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 IC CCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAA CGGGTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCC CGCCGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTG TGGTGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGC CTTTGTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGAC CCTGCTTGCTCAACTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCT GTGACCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAG CTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAG TTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTC ATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGG CGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCA TGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGAC CCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCAT CGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCA CAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGC CACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCG GCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAA AGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGAT CACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatag catcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGAG GCGGCTGCGCAGTACAACCCGGAGCCCCCGGTAAGCCCCCTCTGCAACCAGACCCCCTTCT CCTGCCAAGGCCTCTTCGAGGTCCCATCCCTGTTCCTGTAGAGAAGCCCCACCTTCCTCCCCT TCTTGTGAAATTCCTCTGCCAGTTCCTCCCATGCCGTGTCTGCAGCTTCGCCATGGGTCTTAG CCATGCCCCACATACGTGCACCCCATTCACTACCACCCCTCATTCTTTTCCTCATCAAGCTGCC CAGCCCACTCTGACTTCCCCACCCAGGGTACCTGGGTTTGGGGAGCCGTCCTGGCCGGGTT CCCCTCCCCCTGCTCTGAGCTCTCCTCCCTTTGCAGCCCCCACGCACACATTACTCCAACATT GAGGCCAACGAGAGTGAGGAGGTCCGGCAGTTCCGGAGACTCTTTGCCCAGCTGGCTGGA GATGTAAGTAACpARBI- 604: CAPNS1_ 3_Exogen ous_9 GCTGATGGTTCTGTAGTGCTGCCCGTTGGAGGCCCCGCCCCTGGCACTAACCCCTCCCCCTT ATCTCTTCGCAGCGAGGCGGCTGCGCAGTACAACCCGGAGCCCCCGGTAAGCCCCCTCTGC AACCAGACCCCCTTCTCCTGCCAAGGCCTCTTCGAGGTCCCATCCCTGTTCCTGTAGAGAAG CCCCACCTTCCTCCCCTTCTTGTGAAATTCCTCTGCCAGTTCCTCCCATGCCGTGTCTGCAGCT TCGCCATGGGTCTTAGCCATGCCCCACATACGTGCACCCCATTCACTACCACCCCTCATTCTT TTCCTCATCAAGCTGCCCAGCCCACTCTGACTTCCCCACCCAGGGTACCTGGGTTTGGGGAG CCGTCCTGGCCGGGTTCCCCTCCCCCTGCTCTGAGCTCTCCTCCCTTTGCAGCCCCCACGCAC ACATTACTCCAACtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccct ggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctg gggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggct ctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTC CCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGG GGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGA ACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1 CGCAACGGGTTTGCCGCCAGAA CACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGG CCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTG CGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCC TTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTA 2541 108 WO 2022/093846 PCT/US2021/056689 CGTCTTTGTTTCG1 1 1 ILIGI 1 CTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCT AGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGT GCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGA GGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAA GCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCC GCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGT CCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAA GTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATG GCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGAC GGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGC TGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAA GCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGAC GAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatATTGAGGCCAACGAGAGTG AGGAGGTCCGGCAGTTCCGGAGACTCTTTGCCCAGCTGGCTGGAGATGTAAGTAACCTGG GGTCCCTGGCCCCGTCCTAACCGTTCCATCCCTTCCCTTGTGGCTGCCCTTGCACACACACCC TTGACCATGACAATCCCAGTGTTCCCATTCTCCATGACATTCTCAGACCCCTTTCAGTCACCC CTGACCTGCCCCTAACTTCCGCCCGCAGGACATGGAGGTCAGCGCCACAGAACTCATGAAC ATTCTCAATAAGGTTGTGACACGACGTAAGTGACCGGGGTTAAGGAATAGGGTAGATTCA GAGGCAGAGGGGTCAGAGAGGATTTGACCTCTGGCCTCTGACTTTCAACCTGTTACCCACA GACCCTGATCTGAAGACTGATGGTTTTGGCATTGACACATGTCGCAGCATGGTGGCCGTGA TGpARBI- 605:CBLB_1_E xogenous _10 ggagagttatagcagatggagacaaaaaagggaactgctggggatcaaaccttgtaaagtccttctaagtgatatatga ggactttgacttttattcaaagttagaaggctttgaacaaaagaattatttcatttgtgttttacaatggtcacaagtgccg tagcgagaataggctgTGTAGAGAAGAGATTTTGTGGTTTTCTTTTTTGTTCTCTGTATTCTCTTCC TGAAAAATCTGTTTTCTGCCTAATCATAI 1 ILIGTAAAGAACAATAGACTTGAACGTCTGCTG TTAAGTAACAAAGGTTGACCTAAACCACATAAGGTCAGATTAACTTTTAAAATATCCAAGAT AATGTTAAGTGTATTAAATATGGTTCAGTATGTAATCAAAATATTTGATATTCTCTAGATACT AATCTCttttaatttttttattttttAGCCTTGGtgacgactgtgccttctagttgccagccatctgttgtttgcccctccc ccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgag taggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgc tggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCAC ATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGA GAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGA GGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGG GTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGC CGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGG TGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTT GTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTG CTTGCTCAACTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGA CCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGT TCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCA GCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCT GCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGT GCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGC CCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCG CGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGA CTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAA CGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCAC AACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGC GACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAG ACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCAC TCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatc acaaatttcacaaataaagcaLLLLLLLcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGGCTCT 2541 109 WO 2022/093846 PCT/US2021/056689 AHI IGCGGAATTGGAATTTCTTAGCTGTGACACATCCAGGTTACATGGCAI 1 ILICACATAT GATGAAGTTAAAGCACGACTACAGAAATATAGCACCAAACCCGGAAGGTAAGACI 1 1 1 IAG CAGTAATATTATGTGATATATCCAAAGATGAAAAATTCTCCATGGTTTGTTCCTAAGTAAGT CAGCAATACCCGCTGATGGCATGCTTGGGAGGGGGCTAGAAAAGGTAAAAGACCAAAATG GTGCTTCTTAACATAATGTTTTAAATTGATACATTGTGCTTACTCTGAAACTTGGTATTCATA AAGTGAAAGGGGATATGGTCTCCTTTCTGTTTTCATGATATCCGTGTTTATGTGCAAAATTG AATGTATATATTTGAATACTTGAATACTGTGCTAAAGAACAAATAAATAGAACAGTCTTATG TTCATTACTTTpARBI- 606:CBLB_2_E xogenous _11 CATATTACTCATTTGTGCAATGAATAAAGGATTTCTATTATTATATGGACCCATCATCTTATG ACTGI 1 1 1 1AGAAAATGAGAATTAAATCTTGATTCATTATTAAATAACCTTGTATACACACAT GAAGAGGTCATGACACATAAGACTTTGACCTAATACCTTTTTTCAGATATGTTTCTATAGCTA TCTTGATAGCCTAGGACTGTTTGAGAGAAAATTAATTTAAAI 1 1 1 1 GTCATATTCTTAGCAAA TGCAAAATAATTGAGTTAAACAGAACCCACTACATTTGTTCTGAAATATGAACAATATTCTC AAATATTTGTCTGGTAGTACAAATACAATTATATTAATTTTATTATTGAATTTTGCTGCTTCAA AGGGAGGTATTTCTTAAATGATACTTGATTCAATTATTTCCCTTTTTTTCCACCTTGCACAGA ACTATCGTAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaa ggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggg gtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctatg gGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCG AGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGGT AAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACC GTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCAGAACAC AGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCG CCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGT CCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTG GAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGT CTTTGTTTCGTTIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGA GCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCC ATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGC GAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGC CCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTAC CCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGG AGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGA GGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAA CATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGAC AAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGC GTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGC CCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCG ATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCT GTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattt ttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCCATGGAAAGTATTCAGACAGTGC CTTCATGAG GTCCACC AG ATTAG CTCTG G CCTG G AAG CAATG G CTCTAAAATCAACAATTGA TTTAACTTGCAATGATTACATTTCAG 1 1 1 1 IGAAI 1 IGAIAI 1 1 1 1ACCAGGCTGTTTCAGGTA AGTTTATACTTGCTTAGTCTATCCATTCCCTtcttctctctccctgtcttttctctctgtttctctctctctctgtct ctctctcacacacacacacaTAAACAAACATATGGAAAATAGTGTCATTCCTATTAGTCTGTAATTT TATTGGTATGTTTGGTCATTGTTAAAAGTTTAGAGTGAGCCATTTGGCTTAAGTTTGGAGTT ATCAG ATG CTGTG AG CCTG GTGG CTGCTTGTTAGCTTTG AG AG G ATCCATCCAAAAG AG CT TTGTTTTAAACTCTCTACTTAGTTTCTTACTT 2541 pARBI- 607:CBLB_3_E xogenous _12 TTAAACTTTAGAGGTTCAAAATAAGGATATGATATAGAAAAGATTGAATGGTAGGAGAACA GAATAGGATTTATTTATATTATGACAAACGTGACTATCAGTTAATAAATTGGAGATAGTAAG TTAAGATCATTATTTATATTATGGAAAAATGAAGAAATAGGACATGGTTCTCTAACI 1 1 1 IAA Illi ICIGIGAAAIAAAAIAI IAIGACI IAIIIIAIIIIIAICIIIGIIII 1AGGTAAGACTGT GCCAAAATCCCAAACTTCAGTTGAAAAATAGCCCACCATATATACTTGATATTTTGCCTGATA CATATCAGCATTTACGACTTATATTGAGTAAATATGATGACAACCAGAAACTTGCCCAACTC AGTGAGAATGAGTACTTTAAAATCTACATTGATAGCCTTATGAAAAAGTCAAAACGGGCAA 2541 110 WO 2022/093846 PCT/US2021/056689 TAAGACTCTTTAAAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgacc ctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattc tggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtggg ctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGT CCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCG GGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAG AACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCAGA ACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAG GCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACT GCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCC CTTGGAG CCTACCTAG ACTCAG CCG G CTCTCCACG CTTTG CCTG ACCCTG CTTG CTCAACTCT ACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTC TAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGT GCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGA GGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAA GCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCC GCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGT CCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAA GTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATG GCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGAC GGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGC TGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAA GCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGAC GAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGAAGGCAAGGAGAGAATG TATGAAGAACAGTCACAGGACAGGTAAGAAGAATATTTCAGATGTTTTGGTGTAAAGGTCA TTTATGTTGCI 1 1 1 1ACTTAATAGTTAACCTAAACGTCACCATGTAATTGTTTTGGGGTAAAT GTGAGTCGCTTTGTATATagtcatgtggtacttaacgatggggatactttacaagaaatgcatttttagacaattt cattgttgtgtggacatgatagagtgtacttacacagagctagatggtattacctaccgcacacctaggctgtatgatgta gcctattgctcctaggctgcaaatctatacagtatgttactgtactgaatactgtgggcagttgtaacacaatggtaagta tgtgtgtatctaaatatacctaaacatagaaaaggtatggtaaaaatactgtataaaaggccgggcgtggpARBI- 608: CD2_l_Ex ogenous_ 13_14_15 AGATGAGAAAACCTATCCTTCCCAAI Hill 1G 1 GTGAGAATTAAAATGCAGCAAGAAAACA CACACTCATAAACACATCTGCTTTGGCAAAGGAGCACATCAGAAGGGCTGGCTTGTGCGCG CTCTTGCTCTCTGTGTATGTGTATTATGTTTTATGTTACTGTAAAAGATGTAAAGAGAGGCA CGTGGTTAAGCTCTCGGGGTGTGGACTCCACCAGTCTCACTTCAGTTCCTTTTGCATGAAGA GCTCAGAATCAAAAGAGGAAACCAACCCCTAAGATGAGCTTTCCATGTAAATTTGTAGCCA GCTTCCTTCTGATTTTCAATGTTTCTTCCAAAGGTAAGCATAAGAGTCAAAGAAGTCCCAAC CCAGCTTTCCCTGAAAGTGACTCTCAGTAACTCTTTTGCI 1 1 1 1ATAGGTGCAGTCTCCAAAG AGATTACGAATGCCTTGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttcctt gaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattc tattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcgg tgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCAC AGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGC GCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGG GAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGC CAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCT GAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC 2541 111 WO 2022/093846 PCT/US2021/056689 AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGAAACCTGGGGTGCC TTGGGTCAGGACATCAACTTGGACATTCCTAGTTTTCAAATGAGTGATGATATTGACGATAT AAAATGGGAAAAAACTTCAGACAAGAAAAAGATTGCACAATTCAGAAAAGAGAAAGAGAC TTTCAAG G AAAAAG ATACATATAAGCTATTTAAAAATG G AACTCTG AAAATTAAG CATCTGA AGACCGATGATCAGGATATCTACAAGGTATCAATATATGATACAAAAGGAAAAAATGTGTT GGAAAAAATATTTGATTTGAAGATTCAAGGTAAGTGTTCATTCCCTTAATTGCTTTATTTCAG TGTGGGTGCTATTTGGCAAGTTGGAAAATAGCAI 1 ILIAATATTCCCCAGCGCTGACCTCTG CCTCCAGGGGGGCTATACAGGAAACCAGATGCATGTCTCCTGCCCCAGTGGAGACTGTGGT CCAApARBI- 609: CD3E_1_ Exogenou s_16 AGGATTGTTCTAGTTGATTGGTATGTGTGCACTCCTAGTTGTTAAATATTTTCACTATCACAC CTGGATATACTCAACAAATATTTGTTGAGCCAAATACTCAACACCAGCCAAACACGTAGTAT TTACTTTAGCTTAAGCGAATTATTTAGCCCTGACAGAAGCCCTGGAATGTGGGTCTTTAAGT TCCTAI 1 1 1 IGAGATGGGAAAGCTGAGGCTCACGGAAGGAGGTGACCAGCTCAAGTCTCCT ACCGTCCATGCCAAATTAGAATTCCAGCCTGCCTCCTGACTTCAAGTCCAAAGTTCTTCCCAC GCACTAAAGCTAGCTCTTCAGTGTCCTTTCTTAGGAGGTACTTCCTCCCGCACCACTGACCG CCCCCTCTCTATTTCACCCCCAGCCCATCCGGAAAGGCCAGCGGGACCTGTATTCTGGCCTG AATCAGAGACGCATCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttga ccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctat tctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgg gctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAG TCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGC GGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGA GAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCA GAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTG AGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAA CTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCT CCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACT CTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTAC TCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTG GTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGC GAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGC AAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCA GCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTA CGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTG AAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAG G ACG G CAACATCCTG G G G CAC AAG CTG G AGTACAACTACAAC AG CCAC AACGTCTATATCA TGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGG ACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGT GCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAG AAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGG ACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaat aaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTGACCCTCTGGAGAACAC TGCCTCCCGCTGGCCCAGGTCTCCTCTCCAGTCCCCCTGCGACTCCCTGTTTCCTGGGCTAGT CTTGGACCCCACGAGAGAGAATCGTTCCTCAGCCTCATGGTGAACTCGCGCCCTCCAGCCT GATCCCCCGCTCCCTCCTCCCTGCCTTCTCTGCTGGTACCCAGTCCTAAAATATTGCTGCTTCC TCTTCCTTTGAAGCATCATCAGTAGTCACACCCTCACAGCTGGCCTGCCCTCTTGCCAGGATA 2541 112 WO 2022/093846 PCT/US2021/056689 TTTATTTGTGCTATTCACTCCCTTCCCTTTGGATGTAACTTCTCCGTTCAGTTCCCTCCTTTTCT TGCATGTAAGTTGTCCCCCATCCCAAAGTATTCCATCTACTITICTATCGCCGTCCCCTTTTGC AGCCCTCTCTGGGGATGGACTGGGTAAATGTTGACAGAGGCCCTGCCCCGTTpARBI- 610: CD3E_2_ Exogenou s_17_18 AATAATAAAATAATAACAATACTTAACATTTATTGAGTGCTTATTAAGTCTCAAGCACTGTCT GTACCCAACACTTATCAAGGATTCI 1 1 1 1 CATGTAATCCTCTCAACAACTATATGGGTTAAGT ATCATTTTATTCCCATGAGTAAAGGGATGAGGAAACAGAGGGTTTGTGAGTTGAAAACACA TTTCACGCTTCTCACAGCTAGTGAGTAATAAAGCTGGGACTCAAACCCAGGGCTGTTTGACT CCAGTGCCTCTACCCACGGCCACCACTCTTTGCTTGTCAATGTTGTTCTAAACATATTGAAGG GGGGGCTCTGACCGTGGCAAGCGTGTGAGTAGTAAGGGGAGAATGGCCTTCATGCACTCC CTCCTCACCTCCAGCGCCTTGTGTTTTCCTTGCTTAGTGATTTCCCCTCTCCCCACCCCACCCC CCACAGTGTGTGAGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgac cctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctatt ctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgg gctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAG TCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGC GGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGA GAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCA GAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTG AGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAA CTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCT CCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACT CTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTAC TCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTG GTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGC GAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGC AAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCA GCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTA CGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTG AAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAG G ACG G CAACATCCTG G G G CAC AAG CTG G AGTACAACTACAAC AG CCAC AACGTCTATATCA TGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGG ACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGT GCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAG AAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGG ACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaat aaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatAACTGCATGGAGATGGA TGTG ATGTCG GTG G CCAC AATTGTCATAGTG G ACATCTG CATCACTG G G G G CTTG CTG CTG CTGGTTTACTACTGGAGCAAGAATAGAAAGGCCAAGGCCAAGCCTGTGACACGAGGAGCG GGTGCTGGCGGCAGGCAAAGGGGTAAGGCTGTGGAGTCCAGTCAGAGGAGATTCCTGCC AAGGGGGACGACCAGCCTGGGCCAGGGTGGGTGGCAAGTCCACAGCTAGGTCAGAACAG CTTCTCTAG AG CTTCTATG CACAGCTTCTATTACTGTG ATG ACAAG ATCTCAACAG ACG GTTT CAAATCTCACATCACTCCCCTCCTTCCCATCCTAGAAAAGTGCAAAAAAGTTTATGAAAGTG ATG G G CTTCCTCACATACCTGTCAATG CCTG CAGTCATCCGATTCCG CCCCTAAG CTGTG G G AAGAGAG 2541 pARBI- 611: CD3G_1_ Exogenou s_19_20 ACTGTGACCCATGAACCAGTAGGTATTGGCGTCACCTGGGATCCTGACGTTAGTCTCTGTCA ATCCTTCTCTTTAGTTCATCTATTCTACCCAAAGTGATCTCATCATCTGGTATGCTGTTAGCAG TTTCTTACCTGTATAGTATCTTCCAAATAACATGCCCCAAAATCCCAAAGTTTTACCCCTACTA ATTACAGCAATGTCTCTTTTATTCTTCACCCCCTGACGCAGATATTGGCGTCACCCGAGAGC ATGTTAGTAATGCAGAATCTCCCCTCCCCAGAACTACTAAATAGCACCTGAAATTTTAACAA GATCCCCATGTGATTCATGTGCACATCAAAGTTTGAGAAACACTACTCTAATGATCTCCTGG TATGCAGAAGCAGGGAGAATTTCAGAGGCAAGATCCTTAATAGAACCACGGCTTTTCTCAT TTCAGGAAACCACtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccc tggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattct ggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggc t ctatggG GATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCA CAGTC 2541 113 WO 2022/093846 PCT/US2021/056689 CCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGG GGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGA ACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1 CGCAACGGGTTTGCCGCCAGAA CACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGG CCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTG CGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCC TTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTA CGTCTTTGTTTCGTTTICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCT AGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGT GCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGA GGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAA GCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCC GCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGT CCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAA GTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATG GCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGAC GGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGC TGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAA GCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGAC GAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTTGGTTAAGGTGTATGACTA TCAAGAAGATGGTTCGGTACTTCTGACTTGTGATGCAGAAGCCAAAAATATCACATGGTTTA AAGATGGGAAGATGATCGGCTTCCTAACTGAAGATaaaaaaaaaTGGAATCTGGGAAGTAAT GCCAAGGACCCTCGAGGGATGTATCAGTGTAAAGGATCACAGAACAAGTCAAAACCACTCC AAGTGTATTACAGAAGTATGTAATCCCCTTTGGTCTGTTTGTTGTGAAATTAATCAGTATTTG CTGTTCTGGTGAGC1 1 1 1 1ATCTGGGGTGAAAGTGGAAATAGATCCTCAACAGTAATATTAT CGCCTGTTCTCTTAATTTCAGCTTGCCTCTTTTAAAATACTGTAAGATACTTCCCTCACCCTAT TG A AAAACTACAG CCAGTCCTGTAAAATTTTGTTTACCTTTG G GTG G G CTCCATG GpARBI- 612: CD3G_3_ Exogenou s_21 TTCGAGACAAGCCTGGCCAACATGATGAAACTCTGTCTCTACTAAAAATACAAAAAAAATTA ACCAGGCGTGGAGGCGCGCGCCTGTAGTCCCAGCTACTCAGGAGGCTGAGGCAGGAGGA CCACTTGAACCCAGGAGGTCGAGGTTGCAGTGAGCTGCGATTGTGCCACTGCACTCCAGCC TGGGCAACAGAGAAAGACTCCGTCTCAAAAAAAAAAAAGAGAGAGAGAGAAAAAGAAAA AAGACAGAGCCTCCATCTCCTTGTCCTCTTTCCATCCTCAGGACCATGAAGTACCCACTCCAA ATTCTCACATATAAAAAACATTCAATAAACATGCATCAAATTAATTAATAGAGGATGGAAAA AATGACTTATGACTGTGCTGTCCTTTCCAGCCCCTCAAGGATCGAGAAGATGACCAGTACAG CCACCTTCAAGGAAACCAGTTGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgc cttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtg tcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgggga tgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGG TGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTG GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGC CGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCT ACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTC CTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCG GCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGC TCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGC GCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA 2541 114 WO 2022/093846 PCT/US2021/056689 AG G AG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatAGGAGGAATTG AACTCAG G ACTCAG AGTAG GTG G GTTCTTCAATG CCAATTCTA ATAAAG G ACCCTTG C ATCA ACTGCCCTCGCAATTGCTTCTAAGTCTAGCTCCCTTCCCTAAGCGGCTATAAGCATCAGACTC TG G G G ATCAG G G ATTG G G ACGTG GTTTG G GGTACTCI 1 1 1L1AAAAATTCTG G G G CC ATAC TGATTGTCTTGGCCTAGGTAAATATGAATTTTATGTATCTGTAAATCCTGTCAGAGCAGGGC CTCAAGCCATAGAGATGCTGAATATTAATCTTAACCTACATTTGAAI 1 1 L1CATTATCTACAC TATTAACATTTTGGGCTAATTAATTATTTGTGATGAGGGGCTAGCCTGTGCATTGTAGGAGT TATGGAAGCATCCCTGGCCTCTCTCCACCAGATGCTGGTAGATTGTCCAGTGTGACAATCAA AAATpARBI- 613: CD5_l_Ex ogenous_ GACCTCAGGTGATCTGCCCGCCTCAGCTTCCCAAAGTGCTGGGATTACAGGCATGAGCCAC CACACCTGGCCTAAAATTAAI 1 1 1 1AAAGATCTCTTAAAAAGCAGACACCAGCCCCAATCTC AGACCCCTTGAGACAGAATTTCCAGGACAGGGGCCATCCTGCTGGACAGTGGGTGCCGAG AACACCTTGCCCATTTATCTGAGCTCCCTTCTGACTCTGAAATCTGGAGCCCCACCCTCCTGG GTCTAGCTTCGGGGCTGCCTGGGTCAGGGTCCTCTGGGAAGCCCCTGCAGTGCCCCAGAAG GGACGAAGCTCACAAGGGGCAAGGCAGGCAGCCCACGGGGCAGGAGGGAGCTCAACTGG GCGTCCTAGGGAGAGGGCAGTGAGGGGTGCCAGTGGGGAACCCCTCCCAGCCTGACCCCC ACCACACCTTTCTGACCCCCAGATtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgt gccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtag gtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgg ggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACAT CGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGA AGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAG GGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGGGT TTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCG CCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTG CCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGT CCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCT TGCTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACC GGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTC ACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGC GTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGC ACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGC AGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCC GAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCG CCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACT TCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACG TCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAA CATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGA CGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGAC CCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTC TCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcaca aatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTTCCAGGCA AGGCTCACCCGTTCCAACTCGAAGTGCCAGGGCCAGCTGGAGGTCTACCTCAAGGACGGAT GGCACATGGTTTGCAGCCAGAGCTGGGGCCGGAGCTCCAAGCAGTGGGAGGACCCCAGTC AAGCGTCAAAAGTCTGCCAGCGGCTGAACTGTGGGGTGCCCTTAAGCCTTGGCCCCTTCCT TGTCACCTACACACCTCAGAGCTCAATCATCTGCTACGGACAACTGGGCTCCTTCTCCAACT GCAGCCACAGCAGAAATGACATGTGTCACTCTCTGGGCCTGACCTGCTTAGGTGGGTAACT AGCCAGCCACACGGGCACCCTGGGCCTGGGCGCCAGCCCCGAGGAGACTGCCCGAGGCCT 2541 115 WO 2022/093846 PCT/US2021/056689 GTGATCTAGGGTCTGAGCAGGCTGGTGGAAGGGGTGGGGGGACCCCAGTTTATAACCACT CCCCAAGACACATACCpARBI- 614: CD5_2_Ex ogenous_ GGACAGGGGCCATCCTGCTGGACAGTGGGTGCCGAGAACACCTTGCCCATTTATCTGAGCT CCCTTCTGACTCTGAAATCTGGAGCCCCACCCTCCTGGGTCTAGCTTCGGGGCTGCCTGGGT CAGGGTCCTCTGGGAAGCCCCTGCAGTGCCCCAGAAGGGACGAAGCTCACAAGGGGCAAG GCAGGCAGCCCACGGGGCAGGAGGGAGCTCAACTGGGCGTCCTAGGGAGAGGGCAGTGA GGGGTGCCAGTGGGGAACCCCTCCCAGCCTGACCCCCACCACACC HILI GACCCCCAGATT TCCAGGCAAGGCTCACCCGTTCCAACTCGAAGTGCCAGGGCCAGCTGGAGGTCTACCTCAA GGACGGATGGCACATGGTTTGCAGCCAGAGCTGGGGCCGGAGCTCCAAGCAGTGGGAGG ACCCCAGTCAAGCGTCAAAAGTCTGCtgacgactgtgccttctagttgccagccatctgttgtttgcccctccc ccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgag taggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgc tggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCAC ATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGA GAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGA GGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGG GTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGC CGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGG TGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTT GTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTG CTTGCTCAACTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGA CCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGT TCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCA GCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCT GCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGT GCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGC CCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCG CGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGA CTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAA CGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCAC AACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGC GACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAG ACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCAC TCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatc acaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCAGCGG CTGAACTGTGGGGTGCCCTTAAGCCTTGGCCCCTTCCTTGTCACCTACACACCTCAGAGCTC AATCATCTGCTACGGACAACTGGGCTCCTTCTCCAACTGCAGCCACAGCAGAAATGACATGT GTCACTCTCTGGGCCTGACCTGCTTAGGTGGGTAACTAGCCAGCCACACGGGCACCCTGGG CCTGGGCGCCAGCCCCGAGGAGACTGCCCGAGGCCTGTGATCTAGGGTCTGAGCAGGCTG GTGGAAGGGGTGGGGGGACCCCAGTTTATAACCACTCCCCAAGACACATACCCAGGAGGG GGACTGGAAGGGGCCAGCACCCATCTGTAGGATGGCAATGGAGGACCTAGTTCTGCCAAT CACTGACTTCATCGTCGCCTCTGAACCTCCATTCTCCCATCTGTGAAGTGGGGTGGTACTTCC CGCCTCGCAGGAGGCT 2541 pARBI- 615: CD5_3_Ex ogenous_ tgctgggattacaggcatgagccaccacacctggcctaaaattaatttttaaagaTCTCTTAAAAAGCAGACAC CAGCCCCAATCTCAGACCCCTTGAGACAGAATTTCCAGGACAGGGGCCATCCTGCTGGACA GTGGGTGCCGAGAACACCTTGCCCATTTATCTGAGCTCCCTTCTGACTCTGAAATCTGGAGC CCC ACCCTCCTG G GTCTAG CTTCG G G G CTG CCTG G GTCAG G GTCCTCTG G G AAG CCCCTG C AGTGCCCCAGAAGGGACGAAGCTCACAAGGGGCAAGGCAGGCAGCCCACGGGGCAGGAG GGAGCTCAACTGGGCGTCCTAGGGAGAGGGCAGTGAGGGGTGCCAGTGGGGAACCCCTC CCAGCCTGACCCCCACCACACCTTTCTGACCCCCAGATTTCCAGGCAAGGCTCACCCGTTCC AACTCGAAGTGCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccct ggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctg gggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggct ctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTC CCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGG 2541 116 WO 2022/093846 PCT/US2021/056689 GGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGA ACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1 CGCAACGGGTTTGCCGCCAGAA CACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGG CCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTG CGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCC TTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTA CGTCTTTGTTTCGTTTICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCT AGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGT GCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGA GGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAA GCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCC GCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGT CCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAA GTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATG GCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGAC GGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGC TGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAA GCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGAC GAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCAGGGCCAGCTGGAGGTCT ACCTCAAGGACGGATGGCACATGGTTTGCAGCCAGAGCTGGGGCCGGAGCTCCAAGCAGT GGGAGGACCCCAGTCAAGCGTCAAAAGTCTGCCAGCGGCTGAACTGTGGGGTGCCCTTAA GCCTTGGCCCCTTCCTTGTCACCTACACACCTCAGAGCTCAATCATCTGCTACGGACAACTG G G CTCCTTCTCCAACTG CAG CCACAG CAG AAATG ACATGTGTC ACTCTCTG G G CCTG ACCTG CTTAGGTGGGTAACTAGCCAGCCACACGGGCACCCTGGGCCTGGGCGCCAGCCCCGAGGA GACTGCCCGAGGCCTGTGATCTAGGGTCTGAGCAGGCTGGTGGAAGGGGTGGGGGGACC CCAGTTTATAACCACTCCCCAAGACACATACCCAGGAGGGGGACTGGAAGGGGCCAGCAC CCATCTGTpARBI- 616: chr2_l_E xogenous 106 TGTCCAAAGTGTGTGTCACCTGCTCTGTGTTCACCCACTGGGTTCATCAGAGGGGCACTTGA ACAAAACAGGAATGTCACTGGAGAGGGGAACAAATGCTGTCCCCAAGTCCTTCCCTGCCGT TTAGAGTAACG CAG CCCCTGTCCG CACATCCTCACCCCCATCTG CCCTCTG CTTG CCAG AATT ATCAGAATCTCTCAATTCTAATTTCAGCCATTCTCTGTGAAAATGAAAAGTTAGTGGCAGGC AATGGACACCCTATTGAAATAGAAATTGTTCTTCATATGTCAGAAAAGTCCCAGAGTAATCT GGGAGTAATCTGAGCAAACTGATTCAAAGGATTATTACAATTTCTTAGTCTTCTACTGCTGC AAAAGTGGCACTCTTTGATTCTCATGTTTGAGGTTCTAATTACTACCTCATGCAGGACTTACA AGAGATCAGCCATGCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttga ccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctat tctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgg gctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAG TCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGC GGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGA GAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCA GAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTG AGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAA CTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCT CCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACT CTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTAC TCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTG GTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGC GAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGC AAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCA GCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTA CGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTG AAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAG 2541 117 WO 2022/093846 PCT/US2021/056689 G ACG G CAACATCCTG G G G CAC AAG CTG G AGTACAACTACAAC AG CCAC AACGTCTATATCA TGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGG ACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGT GCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAG AAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGG ACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaat aaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTGCTTACATTGTGTGTAG TGAATCAATGTTATTCTGAAGGGCCTCCTGGAAGCAGTAGGGATTGGAGAATGTATGTCTT TTAACATGATCATTCCCATCCTATGGGGGTTGGGCACTCTTAACTCATGTTGCAGATGAGTA AACTGAGGCTTTTGAGAGTTTGAGGGTGCACAGCTTGAGGCAGAGGTGGAATTCCCAGCTT CATCCAAGAAATCACGAATCTCCAATGGCTTGCACACATCCAGGTTTGCTGGATCCTATTTG TCAAGACCACATGCAGATTAGGAGCCTTCAAACAAATTATTTCCAAGGGAGGGCATC1 1 ILI CTGTAACCCCTACCCTGGCAATTCTCCATGGCCTCAGGGAGTCCAGCCGGAAGCTCTGCAAT GAGTCCTGGGGAACTCTCATCTGGAAAAAGGCGCTCATGACAGGTGGTGCCAACCTTCCAC GpARBI- 617: chr2_2_E xogenous 107 CTACAAGCATGCATCACCAGGCCTGGCTAAI 111ILIAl 1111 1GTAGGGACAGGGTI 1 IGCT GTGTTGCCCAGGCTGGTCTCAATTTCCTGGACACAAGCAATCTGCCTGCCTCAGCCTCATAA TGI 1 1 1 1 1 1 1 1AATGTTAAACCCCTTCTTGTGTTGAGAGGCCTGGCTTGTGTGTTTGAGCGCA GCTG CCTACCTTTG CAG CTGTA AATGTCAG G G CTCCAG G AG G G CTG G CTG G GTCTCCCCTC CTCCCCTGTTGGGTGGGTGGGGCCCTGAGCTTATCCAGGCATCCCTAGGTGGATGGATGGG TGGATGGGTAGGCCCTGGCCTTCAGGGAATGCACTGTGTGTGGTCTTCCAGCCCCAGCAAA GTCTCAGGGGGCCCGAGCGGGAAGTCGCCATCCTCAGGGGGTCCGAGTGGGGAGTCACC ATCCTCACGGTCAGCCGTGGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgcctt ccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtc attctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggat gcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGG TGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTG GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGC CGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCT ACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTC CTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCG GCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGC TCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGC GCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA AG GAG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTTTCGAATTGAG CTCCCAGGGGCGGAGACTCCATTCCCCCGGGGAACAATCTGATAGCCAGAAATGAGAGCA GTGAGTGACTTGGACGCTGTGTGATTCAGGAGGGTCCCAGTCCCTCAGAGTCGCCTGGACA CCAGATTGTATTTACAAAACAGATGGATGAGGAAATGGAGATTGGGTCTTCAAAAGAATTA ACCTCAGATTTTATTTATTTATTTTAAAAATTTTAAI 1 1 1 1 CCCAAGGACCCTTTCCAAGTCAA GAATTGTTTTAAAAAGAAGCCTGGTGAAGGCAAATGCTGTCTGTGGCCGAAGGCACCGTG AGGAGCTGAGGCTGACTTATGTTTCTCCTCTGGGCTATGTGCGCCTCTAAGGAGTTCACACA 2541 118 WO 2022/093846 PCT/US2021/056689 CTTTAACCCCCTTAGGAACCCTACATGATCATCCTCGTTTCTTAAAGAGGAAGCAGAGCCAG CAAACAAGpARBI- 618: chr2_3_E xogenous 108 TCTTGATGGATACCCATCCTTCTCTGCTGTTCTCTCTTTCCTCCATCCTCAAGCACAGGGAGC TTTTGGCGAGGTTAGCTAACTTCGGGGCAGCTGTGAATTAGATACTGGCTGTAAGTTACCTC CAACATCCAGAGCATTTAAACGCTCGGCTGTCAATGATTGTCATTTTCATTGTTTACATATAG TCACATCCTCAGTTTGTGGGGTGGATGCATTTGATTCAATTCAGATATGCCTTTCAAGCTGG CCCTGCTGAGCTGGGCCTGAAAGGCACATGGCTCATCTCATCTGCATGTGACAGTCTCTTTG AAGTCCCCAGAAGTGCCTGCTCAGAGTCATGCTCGGGAGGGAAGAGGTAAGGCACAGAAT GAGTACAGACTGCCACCCAGCCGCAGGAAAGGTGACTGCACACCAGAGGTTCCTGGTAAG GAGGTGACTCACCCGCGAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttcc ttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcatt ctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcg gtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCA CAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGG CGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGG GGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCG CCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACC TGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCTGTCTCACCTGTCCA AAGTGTGTGTCACCTG CTCTGTGTTCACCCACTG G GTTC ATCAG AG G G G CACTTG AAC AAA ACAGGAATGTCACTGGAGAGGGGAACAAATGCTGTCCCCAAGTCCTTCCCTGCCGTTTAGA GTAACGCAGCCCCTGTCCGCACATCCTCACCCCCATCTGCCCTCTGCTTGCCAGAATTATCAG AATCTCTCAATTCTAATTTCAGCCATTCTCTGTGAAAATGAAAAGTTAGTGGCAGGCAATGG ACACCCTATTGAAATAGAAATTGTTCTTCATATGTCAGAAAAGTCCCAGAGTAATCTGGGAG TAATCTGAGCAAACTGATTCAAAGGATTATTACAATTTCTTAGTCTTCTACTGCTGCAAAAGT GGCACTCTTTGATTCTCATGTTTGAGGTTCTAATTACTACCTCATGCAGGACTTACAAGAGA 2541 pARBI- 619: chr3_l_E xogenous _112 TGAGCAAATAGTTCTATCCI 1 1 1 IGACACAI 1 1 1CCACAGTTTGTATAA1 1 1A TTCATAGAATC CTTCTTAGACTACTAATAAATTCCTATGGGACATAGTCCTTTTATATGCGGAGGAATCCACC ACCATGAAATGTTCACAAGAAATGACTTTTAAAATTTTATTTGTGGCCATGCTGATTATGAA HILI GAA1 1A1G 1 Cl GGGC1 GC1C1 1 1 1 1CTCGGAATATGCAAAGTGGGATACTGGCATCTC TGTATCTGGAGAGTTACAGCTTCTGAGTTAAAAGATGAATGGGAAGTAGCAGGAGAGGGA GAGATCAGAAATCTCCACTCCCTGAAACACAGACACTTCACATACCCAGGAGGTAAATTCCT GGCATGAATTGTAACAAGTATACACAGGCATTTGTACATTGTTTGCTTATGTGCTAGATGAC ATGGCAGTCTATGAAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttga ccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctat tctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgg gctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAG TCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGC GGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGA 2541 119 WO 2022/093846 PCT/US2021/056689 GAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 ICGCAACGGGI 1 IGCCGCCA GAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTG AGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAA CTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCT CCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACT CTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTAC TCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTG GTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGC GAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGC AAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCA GCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTA CGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTG AAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAG G ACG G CAACATCCTG G G G CAC AAG CTG G AGTACAACTACAAC AG CCAC AACGTCTATATCA TGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGG ACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGT GCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAG AAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGG ACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaat aaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCAGGGGCCCCACATCTGC AGGCAGGACATTCAGCCCTGTATCTTGCCACTACCATGAAATCTGAGGTTCTTTCAI 1 1 1 IGT TIIICTATTCTGATGAGATTGAGGTACACTGACTCACTGGTAAAGAAGACAATTTATTTGTG AACTTGTAGTCACTCCATTTGACGGCCTCCCTCTACTCACTGAGGCACAGCACGTGTGGAAC AGGAAAAAGGCCTCTGGAGAGCTTGTGTTCCACTGGTTTCTTTGACTTTTGCCAACCAACTT TGCAAATGTTCTCAAAAGGCATTCATTACCTCTGCAGGTGTGAAATAACTCTGCAGTTCAAG GGTTTGTGAAATCACGTGAAACAGCTGAAAGCTGTTCTGGCAAAGCGACCAGAGTCAGAG TTAGCTGTCACCAAGCCACATCCTGGCTTAAACGATGTTATTTATATCTAACTGCACTCGApARBI- 620: chr3_2_E xogenous _113 AGATGCCCATTGTACCACCTACCATTGCTTGACCCCCGCCCATGAGCTGTTCCTTCATACTCA TAACTAAAATGCCAAATGTGTGACTTGAGTAATTAACTAGAGACCTCCAGAAGGCTTTCCTT CTTATTCTGGGTACATTGATATTTACTTTAGTATTTGTTTTGCCTTTAAAGTCATGTTCCCTTT TGATTCTTTAATATCATATCCAAAACGAAGTCCTTTTAACCTATAACAATGCAAATCAAAAGT GCTGTCTTTCAGCTACCTCAAGGATTTAGCAAGCGTTCCTGGAAATCTAACCAACCTTTTAA AAAGTA1 1 1L1A1GGGAA1G 1A1 1 1L1GAGCCCTAAATTATGGATTTTGAAACTAAAATAGA AGAATACTGTAAGTGCAAAACTTCCAGTAGATAACAGAATTTGCAAAATCTCTAATCTCTTG TATGTGCCCCAAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctg gaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctgg ggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctct atggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCC CGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGG GTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAA CCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1 CGCAACGGGTTTGCCGCCAGAAC ACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGC CGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGC GTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTT GGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTAC GTCTTTGTTTCGTIIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTA GAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGC CCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGG GCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCT GCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCT ACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCA GGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTC GAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGC AACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCG ACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCA 2541 120 WO 2022/093846 PCT/US2021/056689 GCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCT GCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCG CGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAG CTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagca tttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGTAGTACTCTCTATAGGCCATTG GAACAGAACATCTGGCTTAAAATAATCTCAGCACCAAAAACGGTCTAACTATGGTCTCCACA ACATAACCCGATGGTTCTCATATTTTAGATGCTTGATGCACAAGTTGAACTGGCTAACAATT CAGACTTCAGGACTTGACTCCCCTGGGAATCTGCAGTTGTTTCCCTCCCCTTGAGTGAGACT GACTGTTGGGAGTAGAATAACCGCATGCTCTGGGTCAGAATGCCTGGCCCTTCAGAGTAAC GGCAGCCATGATCGCTGAGCTCCTACTGTGAGGCACATACTTCGCCACACTAACACATGGA ATCCTTGCAAGCTCCTTACATAATCAGTATTTTATGCACTTTGCAAATGAGAATACTAAGGCT CAGAAGAGGCAAGCTCCTCTCCCACTGTTAAACAGCTAGTGATGAACAGAGCTGGGpARBI- 621: chr3_3_E xogenous _114 ACTCCCCTGGGAATCTGCAGTTGTTTCCCTCCCCTTGAGTGAGACTGACTGTTGGGAGTAGA ATAACCGCATGCTCTGGGTCAGAATGCCTGGCCCTTCAGAGTAACGGCAGCCATGATCGCT GAGCTCCTACTGTGAGGCACATACTTCGCCACACTAACACATGGAATCCTTGCAAGCTCCTT ACATAATCAGTATTTTATGCACTTTGCAAATGAGAATACTAAGGCTCAGAAGAGGCAAGCT CCTCTCCCACTGTTAAACAGCTAGTGATGAACAGAGCTGGGACCTAAACTTGTCTGATTTCC CACACTGCTGCTCCATCAGATTGTTTGCCAGGTTAAGGATTCATGCCAGGACCTTAAATCCC TCTGAATCGACAGAGCTAACCTAAAGGGCACCTTGATTTCAGGTTTTGTTCCCAAACCTATG ACTGTGGCCTGGCCACGTtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttcc ttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcatt ctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcg gtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCA CAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGG CGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGG GGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCG CCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACC TGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatAATGAAGACCCGGTT GGTTCTAGCTTCACAATGAGCTCATTGGCATTGTCCCCACAACCACCACCCCCTCTCCACCTC TG ATCATCCACTATCATTTCTATATG G CCTTTG CCAG G CTTGTCCTCATATCA AAG CTTCTG C CCTCTATGTTTAAATGCATAAGCTTGACAAATGTTTTCATTTGAGAAGGCAAGCTGCCTCCC CGTGCTTGGTCTAATGTGAGCTTGGTAGAGTGACACTGCTGGATTCAGTTTTAGTCATCAAC ACTTCCAGCTGATGCTGATCTGAGTAATTGTCCTATTTAGACTCTGACAGGTGAAAGTCATA GATTCAGGAAACGGAGACTCCCCTCACCCTGCTATGAAGGGGAGTTTGAGAGGGTTGGGC AGCTCTTCCCGGCAGTGGCAGGCAGTGTGGGGACACACGTATGGATAAATTGTTAATGCTC TT 2541 pARBI- 622:CTGCAGGTGGCAGACTTACTCATTCTCATGCTTCAGCTCCAGGGGTTCCCCTGTATGAGTCT TCTCTGCCCGCTCCCACACCCCAGGTAGCATTGCCCCTGCTTGCTTTGTGCCCTCACTGTCTC2541 121 WO 2022/093846 PCT/US2021/056689 chr3:18Exogeno us_109 CACATATATACACATCTCTTACAATAATATTAAATACCAGCCAACATTTATATAGTACTTCTTA TGTACCAAGTACTGTTGTCTATCTATCTATCATCTATCTATCTATCTATGTACACACACACTCA TATTATCTTCACAATGCTATGAAATAGGTATTATTGCTGTCCATTTTACAGATGGGGAAACC AATCTATAATTGGTTTAGTGAGATTTACTGAGCATATCTACAGGTATTTGTCCTTGGTTATAG GAAACCAATCTGTCACTGGTTTCCCCTTCTGTAAAATAAGTTAAATAATTTGCTTAAGCTCAC TCAGATAGTtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaa ggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggg gtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctatg gGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCG AGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGGT AAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACC GTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGCCGCCAGAACAC AGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCG CCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGT CCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTG GAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGT CTTTGTTTCGTTIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGA GCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCC ATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGC GAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGC CCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTAC CCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGG AGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGA GGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAA CATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGAC AAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGC GTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGC CCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCG ATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCT GTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattt ttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGTGTGGTTGAGTCATAATCTGAGCT ACTCTCTGGCCCAAACTGCTTATTGTAACCACCACATCATATGGCCACTTCAGCACCAGTCAC ACCTCATTTTACTTGTTGATGTCTCAGTTTTCCCCTCTATTCTGCGGGCTACTTGAGAAGACTT CTGTCTTCTTCCTCTAGGTATCTCTGTGCTTGACTCAGTATCGAGACCATAGGTGTGTGGGT GGGGTTAATCCACACTTGCTGAACACATGTGTCCGTGCCCAATGTCCCTGTGCATAGTGGCT ACTTCCCATGGTTCACACGCATCTTCATGGCTCTTGTTTCTTCCATTCACCCATCCCATGTCCC TGGCCCTGTTCTCAGTGCTGAGGATGGAACCTCATTGCTGCTGCTTCCAGCCCTGGCCCTGC CCCTGTTTG G G G CTCAGTG CTTCATCCCGTG G AG CTCA AG G G GTG CTGpARBI- 623: chr3:1865Exogeno us_110 CTTCTCATCCTCACACCCATTCATTTCTTAGTTTCCCATACTCTGACTTCTACTACCCCAAGTTC ATAAAGACCTCATGAACACAACCTGGAGAACGCCCTCAGCCTCATCTCACCTCCCTGCAACA CATGGCTCACTTGTCTGCTTCTTCCTTCTTAGAGTCCTCTCTCTGGTTGACCTGTCAAAGATG GGATTCTCCTGTTAACGACCCTGACTCCTTTGTCTCCTTCTACAAAGATAATGCACTGACTTT CCAAATGTACTAACTAGTATGATCATCACTGTCTACTGTTGCATCGAACCACTACTAACCTCA ATAGGGAAGGCACCAGGTTCAAGAGGCCAAAGAAGAGACCCAGAGCCAGCAAATGAGAC ATGGGGTTTTATGAGGGGCTCACATAGAGGGGAGAGAGTCCAGTGGCAGTGGGCTGGGC AGGAGAACCACCTTACtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttg accctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattct attctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggt gggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCAC AGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGC GCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGG GAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGGGTTTGCCGC CAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCT GAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG 2541 122 WO 2022/093846 PCT/US2021/056689 CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatACGTGGTCCAGTGGT GGGAGGCTGGAAAAGAGATCTGTCTTGCCTACAGTTCAGTGGTGGCGGGTTGGGCAGGAA AACCACAACTGCCTGCAAACATCATGCAGTTTACATAACATTGTCACTTAGCAGCCTCCCCTA ACGACCTCCACCTGGCAATCTTCATTTAACCCAAAACTCAAGGCCTCAATCCCCTGTATGGA CCATGTTTCATGGGACAGGCCAGGGGCTCAGAAGTTTATCATAGATAAGGAATGAATCTCC GGGTTGGCCACTCCTGGATTCCCTAGCTTGGAACACACATTCAAGTGTATCTGCCATTCTGA GTGTATTCTTCAATTATTGCTGTCAGGTGTGTTGACCCTCTATCTACATAAGTAI 1 ILICAAA CCAGGGCCCTACGATCAGCATCAGCATCACCTGGGGTATATGTGAAAAATGCAGCTCCTGG ACCpARBI- 624: chr3:1865Exogeno us_lll GGGCCAAGCAAGCTCTGAGACAAGCTGTCTCACCTCCTCATCTCCTGAGCACAACTCACCCA CAGCTCTGCCCTCGCCTCCACCTACATCATGCCTTCCTGCATGCCAACTTCCCTCTGAGGTTC CCTTCACCCACTTACAACCACAGCCTCCTTCCGGACCTCCCCTACACGATGAACAGTCTGCCA GTTAATATACATCAAGCTGCCACCATGAAACAGCTCGGAAAGCCCCATTTGTTCTCAATAGC ATTCCAGCTAGAAAGACCATCCACCACCCATGGCCACTGAAGAAGGTCCTCCCCTGAGTGC CAGGCAGTGGGGCTCCTAACTCTGGGCCCCAATTAGCTTAGCTTGGGGGAGCAAAGGACA GGAGCACTGTTCACCCAGTTGGACTAACAGCTCCACACTGTGCCTAATAGGAACCTCCTTCT CACAGGTGGCACCTTTGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttcctt gaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattc tattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcgg tgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCAC AGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGC GCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGG GAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGC CAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCT GAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT 2541 123 WO 2022/093846 PCT/US2021/056689 GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTGAATCAGGGTCTGT CCTGAGCCACCCTCCCTTGGAGAGATCTGAGCACTGAGAACCACAGAGCCTGGGACACCAG CACAGGGTTTGAAAAACTCCACTCCCAGTCAGCTGCGGTGGCTCATGCCTGTAATCCCAGC ACTTTGGGAGGCTGAGGTGGGTGGATCACAAGGTCAGGAGTTCGAGACAGCTTGACCAGC ATGGTAAAACCCCATCTCTACTAAAAGTACAAAAATTAGCCAGGCATGGTGTTGGGCACCT ATAATCCCAGCTACTCGGGAGGCTGAGGCAGGGGAATTGTTTGAACCTGGGAGCTGGAGG TTGCAGTGAGCCGAGATCGCACCACTGCACTCCAGCCTGGGCGGCTGAGCGAGATTCTGTC TCAAAAAAATGGGAAAAACATCATTCCCATGTGTGTCCTGGTTGCTTGTCTCTTTCAAAGTA CTGCATACTpARBI- 625: chr8_l_E xogenous _115 CCACATCATGGACCAGAAGCCACTTGGTCTGGTTGTGAGGATGACGGAACCTTGCCCGAGG AAATGGGCAATGAACAGGAGCCTGTTTGTTTCTCCTTCCAGCTCCTGACCTGTCTAGCTCCT GACCCTCTCAGTGTCATTCTTGCTCACCCCTGGCCCTGCTCCCTGGATATGCAGACAGGATG GGCTTCTTCCCTTTAGACCTTCACTTTGCTCTTTTGGACTCCTCTTCTGGCCTTGCCTTCCCCT GGTGTCATCTGCTGGCTCCCTGCCTGATACTGCCACACTGGTCATGCTGGCCTCCTGGCCTT TGGTGACACCGCATCAGCAGGCTCCTGCTTCCCTGTCAAGGGATACAAGCCAGCACCGGTC TTTCGCCACAAGGTATGTGTGTAAAGATTGCTTCCTGTACTTGGTGTCCACAGGATTTTAAA GAACTCCTGGCCCACTtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttg accctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattct attctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggt gggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCAC AGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGC GCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGG GAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGC CAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCT GAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCGGAACTCTACGCTTG AAACAGAAACATCTTCTCAAAACACCTCTGGTATTGGCCCA1 1 1L1L1ATTACTGTTTCTTGT GGTTTCATACTGAGG 1 1 1 1 IGGIGCAI IGCAAI IGCCCIGGAGI 1 IAI 1 1 1 IAGTAATAAAG ACAGAGTTCAATTAATGTCAAAACATGAGGGTAATTGCAGAGGAAGGATTAGTAAGTCTAG GGGAAAATGTGCCCAACTTTTTTTCTTCTGATAACATCTTTCACTGATCATACACCGTCACAC CCACAGACACGGAGCTTCCTCCGTGATGTCTGCAATGCACTAGGCCCAGTCGGGGAGCAGT GGCTGCGCCACCACCTGAAAACGAAAGCATTTCTGAGTCTCTTTCAGTCCAGCTCATCTAGC AGCCAGCCACACAGGTGACCACCCACCGTAGCTGTCACTATGGGTGATGATTATCATTATG G 2541 pARBI- 626: chr8_2_E AGGATCTTTCTCTCTACAGTGCCTCTTGTGGGACGGGTTCTGCTGATGGGGGCTGTGTTTGG GATCTCGCCTGGAAACACGATCTCTCCAACTTTCCCTGGGAGCAGAGCCTTGGGTCTCACTG AACCCACCTCCCCAGCACCTTGTGTGGTGACTGGCAGGAGGTAGCCATTCCCTCCTGTCCTC TCTGCCCTTGTCCACTTTCCTGTTATGAGTCAGTTGCTGAGATAGGCTATGAGGAGTTAACA 2541 124 WO 2022/093846 PCT/US2021/056689 xogenous _116GAGTGGATAAAAAAGAGCTTTGTCCTTCTTTAAAGCCTTCAAAATATACAGATGTATTAGTC AGGGCTTTCCAGAGAAACAGGACCAATAGAACATGAAGATAGATGCGTATCCATGTCTATA TCAATATCTACCTTGATATTTATATCTATATCTAGGAGATTTATTTATTATAAGGTATTGGCTC ATGCAATTATGGACCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttga ccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctat tctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgg gctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAG TCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGC GGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGA GAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCA GAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTG AGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAA CTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCT CCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACT CTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTAC TCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTG GTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGC GAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGC AAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCA GCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTA CGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTG AAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAG G ACG G CAACATCCTG G G G CAC AAG CTG G AGTACAACTACAAC AG CCAC AACGTCTATATCA TGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGG ACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGT GCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAG AAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGG ACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaat aaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCAGAGGGGTCCTGTGATT TGCCACCTGCAGGCTGGAGACCTAGGAAACAGCTGTCGTGTCACAAAGGGCAGAGGGCTG GAGAACCTGTAGTGTAGATTCCAGTCCAGATTCGAAGGCCTGAGGACCAGGAATGCCAAG GGCAGGAGAAGATCGATGTCCCAGAACAAGCAATCAGGCAGAGATGAAATTCAACCTTCC TGTGCCI 1 ILIGTTCTATTCAGGCCTTCAGTGGGTTGAATGAGGCCCAACCCACATTGAAGA GGACCATCTGCTTTACTCAGTCTCCTGGTTGAAGTGATAATCTCATCTGGACATACTCAGAA ATGCTGTTTAACCAGCTCTCTGGAAATCCTGTGGCCCAGTCAAGTTGACACACAAAATTAAC CATCACACTGCAGAGACACAGTCTATCCCAATACCTGTATTTACTGGGTAACGTGCATCTCA GCTCpARBI- 627: chr8_3_E xogenous _117 TAATAATGACTCTGCTGGTAA1 1 1 GTGTCCTTCTGCTTGGAACTGTTTCC1 1 1 1 1 AG 11 IGGTC ACCCTCCC AG AG CTG GTTTCAATG G G G G CATACCC ATTATG G G ATG CAG G G CATCCTG CAT CCTGAGGAATTTTTTTTCCTCCAAAAATGAAACCTTGAAATGAGGACATTGTCCTGTCCACG GACTGCACAACAACACTGAGCCTCAAGGACTCATACTGGCAI 1 1 1 1CTTCTTTTGCAGAGTG TGGGCACCCTGGCTTCAAGCTCACGAGAAACCAGGTCGGGATTTAAACAATGTTGGGTTAA AGCAAAGTTTCATAAAGACAGAATCAAGAAAAAAAGAAAGAGAAACCAATCTAAGTGCCA TCCTCCCTGAGTTGCATCTTACCTGAGTCTTCAGCCGCCGCCCCCTGCTGCTGTGGGAGGAA ACGGGAAAGTGACTGGCCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttc cttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtca ttctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgc ggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCC ACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTG GCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTGG GGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCC GCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTA CCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCC TGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGG CGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTC 2541 125 WO 2022/093846 PCT/US2021/056689 AACTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGC CTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGG GGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTC CGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCAC CGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGC TTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAG GCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGA GGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAA GGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTA TATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATC GAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGC CCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCA ACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGG CATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaattt cacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatATGGGGACAGG GGTCGGGGGTGTGAGGGTTAGTGGTAGCAGGGAGGTAGCACTTCTGTGAAGCCGGAAAG GAGACCTGAACCTGGCTCTCTGCTTTGCTGCTTGCCAGCCCTCTGGCTGGGAAGAAGGCTCT TGGCTCTTGTGAGCCTCGGTTTCCTCTGCAGAGTGGCCTGTTCTGAGGACAGGCTGACATTG CTGTCCATCAGTCTTCCAGGACCCTGAGGATTTCAGCTCTACCCATGGGCACTGAACTGGAA CATTCACTGGTCATTTGCTTTCG IIIIIIIIIIIIGIIIGIIIGIIIIIIGATACAGAGTTTCAC TCTTGTTGCCTAGGGTGGAGTACAATGGCGTGATCTCAGCTCACCACAAGCTCTGCCTCCCG GGGTCAAGCGATTCTCCCCAGTAGCTGAGATTACAGGCATGCGCCACCACGTCCGGCTAAT TTTGTApARBI- 628: chr9_l_E xogenous _118 AAGTCAACAACAGGCTCCAGAAAAAAATGGAAATATAAATGGTCCCCAATTTGGCATTTTG GAATTTGAGGCTTATATAGTATGAGCAAAATAAACTCCTCCTGCTTCTATGAATTCTTTGCAC Hill CTCTATAATTCCTTATCAAGCAATGGGTTTGTCTGTTAACCAAGACTATACATAAAAT GTATTCCCGTAGTTCCTTTTATTACATTTTTTCTTTGTTGTTACTAGTGGAGAAGCTAACAAG AGCAGAATTTCCTGCCCAACCGTAGCAAATACAGAAAATCAAAAAGAGAAGCTTTGATACA GCCAGTGTAGATACAGCTAGGACGTCATGAATCAGAGCTCCCACACACGATGATAATGGAA ACATCTTATCCATATCTG ATTTG CTCACATATAGTTATTTAG ACAACAAATTTTACATTCCTG G ATAGGGAGCCTCCGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgac cctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctatt ctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgg gctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAG TCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGC GGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGA GAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCA GAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTG AGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAA CTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCT CCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACT CTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTAC TCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTG GTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGC GAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGC AAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCA GCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTA CGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTG AAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAG G ACG G CAACATCCTG G G G CAC AAG CTG G AGTACAACTACAAC AG CCAC AACGTCTATATCA TGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGG ACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGT GCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAG AAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGG ACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaat 2541 126 WO 2022/093846 PCT/US2021/056689 aaagcalllltllcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatATTTGATTTCAATCTCATA GTCCAGGTAGGTGTAAAATGACTGCCAAGCCAGCAGACATAAATCTGTATTATCTCATTTTC ATCACAGTCTCTGCATTGGGAAAAAAATGTGAGTGAAAAGACATTTICTCCCACCTTGTTAA GTACACAATTACATAGTTTAAAGAAGATAAGAATTTCAAATTGTTAGAATGATATCATTATT CAAATGATTCCCTGAGAACTTCAAGTATTCCCCTTCCCCCAAATGTAGGCAGGGCAAAATAG AACCAGTAGGAATGAAAAATGTTAATTGTTTCAGGTTCTGTAATTTTGGGTTTAATGACTCA GG CTATGTGCTACTG AGTAAAATACTCATCTG G AG AAAAAG ACTGTTG CATG ACATATTTCT GATTAAGGACAATTTAAACTAATTCTAAGAAAACTCTTACATACTGCACATGCCATAAApARBI- 629: chr9_2_E xogenous _119 GATTAGGTCTGGAATAAGATTGCACCATGACTAAAATGACTTCTTTAGCCAATGACATTCCT GAAGATTGGATCAGAGTAAAGTTAAACTAACCTACTCAAGGAAGACTTTCCTAAATCAGCC CCTTTGCTGTATAATTTAGTATGGAGAGCTGATTGTGGG 1 1 1 1 1CTTGTTTCATTGTTTAATA CATAGAGGTTTCACATTTCATTTTGAAACAGAAAGAGGGACTGGAAGAGATAAGTTAGTAT GAGTGAGGAAAAGATTAGAAGGTAGAGATAGGATCGCAATGCTGTTATCACCTTTGCTTTA TTGATAATCTCAGGAAGGACTAGACTGCTAAGAAAGAGGAGCCCAGATTGGAATAAAAGA GACGATGCCAGGATCAGCCTGTGAGAGGATGTCTCACTTAGTACACCTCAAGGATCATGTC AGCTGAGCATCTATACCCCGCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgcc ttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgt cattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggat gcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGG TGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTG GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGC CGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCT ACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTC CTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCG GCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGC TCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGC GCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA AG G AG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGTGATGAATATT GCATACAGACTCTGCCTTCAAGTCATCCCCCATTCGACAAGCATTTATTTAAGGTTCTTACAT TCCAGGACTTGTACTAGATGCTAGAAACAAACAGATAAGGAAAACGTAGGAAAATGCTTCT CTCAGGAAGCAATATTGTATATGAGTGGTGAAGAGCTTCAAATCTGGGGCCAAACTGCTGG GTTTG AA ATTTG G CTTG G CCACCTACTG G CTGTG AAATCTTG G G CAACTTTCTTAATCACTCT GTGCCTCAGTTTCTTCATCTGTAAAATGAAATAGCCATAGTACTTATTACAAATAGGTAATA ATTAGTGAGAATTAATTTGAGTCAATACATAAAAATGACTCAGAATAAAAGACCAGCTAAG AATATATACACACATACTTAGCTACTTATAATCTAGTAGGAAAGATGGGTATGTTATCAGAG GACTT 2541 pARBI- 630: chr9_3_E xogenous 120 CAGATAAAAAAAGCTGAAGCTCAGGGATATTGTCATTTACCCATGAGCTCACAGGCAGGAA GTG GTG AAACTATCATTAAACTACG GTTG G CCTTGTTCTTTTGTG GTTTC ATTTCACTA AG CC TCTGACACCCTGACCTCAACTTCCTTCTGTAGATATGTCACCTGGCCTCCTTCAGTCTAAGAC ACTACACACTGGCCACACACTTTGTCATCCTCATAGACTGACAACCTGCTCTCACATACCCTG CTTTCTTACTGTGTAGGCTCTCTTTTCTTGCTCAGAATGTCCTTCCCCACTTCTTCATGTGCCA ACTCCTAGTCATCCTACAAGAACCACATTCACTTTAAGTTTCTTTTGAAGCCTTTTCAGTGTCC 2541 127 WO 2022/093846 PCT/US2021/056689 CATACCCTGATCCCATTACCTCTTCTATGTATGCAGGGCTTGCTTCATGCTTGTGTAACCCAA GGGCCCTGCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaa ggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggg gtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctatg gGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCG AGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGGT AAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACC GTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGCCGCCAGAACAC AGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCG CCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGT CCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTG GAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGT CTTTGTTTCGTTIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGA GCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCC ATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGC GAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGC CCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTAC CCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGG AGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGA GGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAA CATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGAC AAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGC GTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGC CCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCG ATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCT GTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattt ttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatATTTGATTTAACACATTTTAAAATTC TTAACAATTTATGAAAAAGGAAACCCATATGTTCATTCTGCCCTGGACCCTGCAAATTATGC AGCCAATCCTGTGTGTGTTTTTTCATGTTGCGTAGACTCTATTACAGTCAGTAACATATTGAG AAAGAGTGTGTGTCTCCTCTGATAGTCTATGAGCTCCTTGAAGCAAGAGGCTTGTCTTAGTC ATTGCTGTATCCTCACACCAGACTCTACGGGATGCTCAGGATTCACCTGTTGATCTGTGAGG AAGCCCAAGGCTCAGTTAATGCCCCCCACCCTCCTTCCATAACAGTCTCCTGATTAGGAAAC AGTGCTTGACCTCTAGACAATCTGAGTATCCACTCCAGGAAGTGGAACATTGCCTTCCCAAT GTTGAAACTGTTAGCACTCAATCATGTTTCAGGAACATATAGAAGGTATGTpARBI- 631: chrlO_l_ Exogenou s_90 TGGACCTTATGCAGGGTAATAAAAACCAACACGTGGGGCCTGTGCTGTAAGGTGGCAGAG GGCGATGACTCACCCCACTCATGCAGGTTGAGTCATTTCAAGGCAGAGTTGTGCCAGTTCA GTACCCAGTAATATTTTCCAGTCGACGAGTATCAGTGAACAGGAGATAACCAGTCAI 1 ILIA GATTCTGCTCAGAGTCCCAGCTTAGAGGCTCCACCAGCTCAAAGAGACGGGATGGCAAAAC AGCCACCTTAATTTCCAGATCATCTGCCAGCTCATCTGCCAGCTGACACACAGCCCATGGCT CCACTATTGCCAGTGCTGTAGCTGCACCAGACCAATCTGGTTCAACTTTTATGTAACAAAGT TGTGATTTG1 1 1 1 1CAGTTGCCCGGGACTCCCAGGTTGAAGATCATGAGCATGCCCTGATGA GCCAAGGCATGCAACCACAGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgcct tccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtc attctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggat gcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGG TGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTG GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGC CGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCT ACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTC CTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCG GCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGC TCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGC GCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG 2541 128 WO 2022/093846 PCT/US2021/056689 TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA AG G AG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGGGAACCTAAG TGCTTGGACTGAGGAGTGGGGACTGAAATAAGAAGCGGACACTGCAGGGCAGGATCAGG ATCCAATCAGATCGAGCCCTGGCATCACCTCATGGCAGGATCTAGTCAGATCGTGGCTTTTG ACATCACTTCATTGTGAAATCCAATCAGATCACACCTTATTACCCTATCCTTATAAAACCGGA CCTAGCCCCCAGCTCGAGGAGGCACTGCTTTGGGAGTTATCCCAGGTGTTCTTGTTACTAGT TG CAAG G A ATAAAATCCTCTTG CTAAATCCTCCTTG GTTGTG C AG ATGTTG G CATG G ATGTG GAGAGAAGGGAACACTTACGCTTTGTTGGTGAGGATGTAAATTAGCTCAACTCTGTGATAA ACAGTATGGAGAGTTTTCAAAGAACTAAAAATAGAACTTCTACTCAACCCAGCAATCCTATG AGTGCATGpARBI- 632: chrlO_2_ Exogenou s_88 ACATCTAATCCCACACCATG ACTAATAAACATG G CATG CTG CAATG G G CATTAATTTATG G G TAACAG AAG CAG ATCCAAG CCTTTTAG CTAATTAAATAAAAATGCACCATACAG CAACCATC CTGCCTGCTTGGGTGTAAAATAGAGAGGAGAAAGATGGCATGCTGGTCATTGAGAGATAA TTACCTGCAATTTCAGAGCTGGAATCTAGTGACAACATAAGAAAAATAATAACCTCTCTGGC TGTTAGGATTCTCAGTTCTAGCTGCGAGCAAGGAGCAAAGGCACCCACAGACTTGCCAAAC CTATGTCAGGAATGACGAATAGAAGGCAGAAATCCACATCCCCAGGTGGTAAAATTGTTAT CCACCTTCGTCACCTCTTTCCTAATGGAGGAAGTGAGGACAGGCAGCCTTGGAGTCCTACTT GAATGAGGCCTGGACCTTATtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgcct tccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtc attctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggat gcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGG TGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTG GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGC CGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCT ACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTC CTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCG GCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGC TCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGC GCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA AG GAG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGCAGGGTAATA AAAACCAACACGTGGGGCCTGTGCTGTAAGGTGGCAGAGGGCGATGACTCACCCCACTCA TGCAGGTTGAGTCATTTCAAGGCAGAGTTGTGCCAGTTCAGTACCCAGTAATATTTTCCAGT 2541 129 WO 2022/093846 PCT/US2021/056689 CGACGAGTATCAGTGAACAGGAGATAACCAGTCAI 1 ILIAGATTCTGCTCAGAGTCCCAGC TTAGAGGCTCCACCAGCTCAAAGAGACGGGATGGCAAAACAGCCACCTTAATTTCCAGATC ATCTGCCAGCTCATCTGCCAGCTGACACACAGCCCATGGCTCCACTATTGCCAGTGCTGTAG CTGCACCAGACCAATCTGGTTCAACTTTTATGTAACAAAGTTGTGATTTG 1 1 1 1 ICAGTTGCC CGGGACTCCCAGGTTGAAGATCATGAGCATGCCCTGATGAGCCAAGGCATGCAACCACAG GGGAACCTAApARBI- 633: chrlO_3_ Exogenou s_89 TGAGGTCTTGGTATGTTGCCCAGGATGGTCTCAAACTCCTGGGCTCAAGCAATCCTCCTGCC TCCACCTCCCAAAGCGCTGAGATTATAGGCATGAGACACAGAGCCCAGCCACTGTCCGCAT TTCTTTCCTG G CTTCCTTACTG G GTTCTCTACTTTCACTCTTG CCTTCTTCCTCTCTTCC ACCAG CATAAGTTTTAGAAACTGCACTTCTGATCATGCTGCTCTGCTGCTTAAAATCCTTCATGCAGA TCATGTAAGACCTTCCTGATCCAGTGCTGCCTTGCCCTCTAGAACCCAGGGTGCC 1 1 1L1CCC CTCTGCAGTTCTACTGCGCCACCTGCAG 1 1 1L1CTCTCCTGTGTTCATGTGTCTACTCCCTCTG AATGGTAGGCTCACACCCTCCACCTGGCCAACTCTTACTAAATCTTGGGCTTCAACTCAAGG ATCACCTTCAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctgga aggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctgggg ggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctat ggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCC GAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGG TAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACC GTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGCCGCCAGAACAC AGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCG CCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGT CCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTG GAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGT CTTTGTTTCGTTIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGA GCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCC ATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGC GAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGC CCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTAC CCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGG AGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGA GGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAA CATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGAC AAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGC GTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGC CCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCG ATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCT GTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattt ttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTGGTTCACTCCACCAGGCTGGGCTG TGTGTCCTGCCCAGTTCCTATAGTGCCCTAACTCACTTTTTTAAAAAAATACTTTAAGTTCTG GGGTACATGTGCAGAACATGCAGGTTTGTTACATAGGTATACACTTGCCATGGTGGTTTGC TGAAGCCATCAATGTCATCTACATTAGGCA HILI CCTAATGCTGTCCCTCCCCTAGCCTCCC ACCCCCCAACAGGCCCCAGTGTGTGATGTTCCCCTTCCTGTGTCCATGTGTTCTCGTTGTTCA GCTTCCACTTATGAGTGAGAACATGCGGTGTTTGGTIIICTGTTCCTGTGTTAGTTTGCTGA GAATGATGCTTTCCAGCTTCATCCATGTCCCTGCAAAGGACATGAACTCATTCTTTTTTATGG CTGTCCATTATTCCATGGTGTATGTGTGCCACATTTTATTTATCCAGTCT 2541 pARBI- 634: chrlO_l_ Exogenou s_92 CCTTCCACCCCCTTCCTTAATAGTTTTCCTCCTCCGCCTCCTGCACGGCCTCCGCCTCCGCCTG ACCGTCCTCGGAAACCTCCCAGCCGCAGCCCGGCCCTCCCCAGCGGCCTGAGTGGCCTCCT CCCGCGGCGCCCCCCAGCTCCGCACCTCCCCAGCCCCGCCCGAGGCGCGCCCAGCGAGCGT GACCCCGACCCAGGGCCACGGCTGCGCCCGTAGGATCGCGGGCGCGCGGGTCTCCATGAG GGACTGGGAGAGATGCGTCACCCGCTAATCCCTCAACTGGGTCGCACCCGGTCTGCCTTGG TTGGTCCCTTCTGATGGCGGAGGCGGGACCTCGACTTGGTGGCCAATGAGGAGCCTCGTG GGGGTGCTCTCGGCTGCCATGGCAACGGAGGGGCCGCCCGCTTCCCCGCGGGGCGAGGCC GGCTCTCCCAGGACTGGCCACATtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgt gccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtag 2541 130 WO 2022/093846 PCT/US2021/056689 gtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgg ggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACAT CGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGA AGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAG GGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGGGT TTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCG CCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTG CCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGT CCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCT TGCTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACC GGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTC ACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGC GTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGC ACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGC AGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCC GAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCG CCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACT TCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACG TCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAA CATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGA CGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGAC CCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTC TCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcaca aatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTGCAGTCAC GCGCTGTGGCCCCAGTCCTGTTAGCATGAGGTGGGGGTCAGAAGTTGAGGAACAACTCGG ACCTAAAGCCTTGACAATTGCCAACAGTGTAGACAAGTCCCAGCATGCCCAAAATTTATAAG AGAAGGCTGCCTGGAAGAGGGACACGATGAGGAGGGTCTGCTGAAACGGACAAAGAAAC CCAGTTCAGTGCAGTGGAGTGGACATGGCACGGGCAGGGCACGGAGTGGGGTCGGTGCT TAGTAAGCGGATTAGGGTTTCCAAGCCAAGACCCACCCAGGGCAGGATGGGGAACCAAGG TGAGCAGGTGCGCTGAATTGTGGGTCTCACACTGTCCTTCAGTGTCCCGCAGGAAGAGAGA GCTAAGGATCACCAGGGTCATTCCCCTGCCTCAGGCAGCCTGCACTCCACCTTAGGTACAGT CATGTCCGGTCTTCAGCApARBI- 635: chrlO_2_ Exogenou s_91 TGATCCTCCCACCTCAGTCTCCCAAAGAGCTGGGATTACAGGCATAAGCCACCTTGCCCCGC CAGI 1 1 1 1AGCCTGTCAGCTCTTTGAGGGACACTTGTTATGGTCATACCCACAGCTTTGACCC TTACCAGGTGGTCAGGTGGATGAATGAATGAGTAGAAAGAAGGAAGAGAAGGCAGGAGG GAGAAGAGGAAGAATGAAGGAAGGGTTGAGTTTGTTCTGGAAGCTCCCAGCTTCCATCCG CACCACACTCTCCCTCTGTCCCCAGGACACCAGGGAACTGACTCAAGGCTCTCCTCTTACCA GGTGCTGTGTGGGGTCCAGGGAGAAGAGCCCATTTGAAATGGGGCACTGGTCTAAACTCT GGACCTGCTGCTCACTATTGACTGAACTTAGCCACTTAAATATTCTCCTCTATAAAATGGGA GTGACCATAGCAACTACCTCGCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgc cttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtg tcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgggga tgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGG TGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTG GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGC CGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCT ACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTC CTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCG GCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGC TCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGC GCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT 2541 131 WO 2022/093846 PCT/US2021/056689 GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA AG G AG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTGAATTGTAGG GAGACCCAAAAAATGTATATGAATACATTTGTCAACTAAAGAGTGTTAGGGATTATCTCAGT GGAGGGATAGGCAGTGCAGGCTCTGGAACCAGACTTCTTGTGTTCACATCCCTGCTCCACT GCTTGGAGACCTTTGGCAAGGTCCTTAACTCCTCTGGACCTCAGTTTTCTCATCTGTAAAACA GGGATTATACTAGTTCCTACCTCACAGAGTTGTGAAGATTAAATGAGATAATGCATGAAAG GCTTTTCAATAAGAGCAGGGCACACATTAGGCATGATGTCCATGATCAAGTGCCTAATATGT GCCTGCTCTCAGGAAGGATGCTGTGAACTACTTCACACTAAAGTGTAAATGAATGATAAGA TCTACTATGCTCCACTCATGCCTGTAATCCTAGCACTTTGGGAGGCCGAAGCAAGTGGATCA CCTGAGGpARBI- 636: chrlO_3_ Exogenou s_93 GGTGAGGTCACCCTGGGTACCTGGAGTTACTCAGAGTGACACTAGTACACGCCTGGCAGG AGTGATGGATGAGCTAGGCTCCAGGAAAGCAGGTGGGGCTGGAAACCACCCAAGACAAG GAAATTGTTGGGTTTGAAATTCCAGGTAAGCAGAGTATGGCCTGAGAGCAGCGGCAGAGG CTGAAAGTGGGCTTGGTCTCGGTAI 1 1 1 1 GAGGCTGAGGTAGCTCCAACTCTCTCCCTCTGA GTCAGCACCCCACTTAAGACAGAAATACTGAGATCTGCGACCCCAGCCTCCCCCACAGCAA CTCCACAGTCCCCAAACCTTTGCTCCGCTGGGTCCTCCCAAGTATGGTAGCTGACACAGCCC TGAGCAGCCCACTGTCCTCTGCCCTGCCAAGTCTTCTCACTCTTGTCACTTTGTCCTACATCAT TTCTTTGTCTGGCACCCCTCCTtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgcc ttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgt cattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggat gcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGG TGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTG GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGC CGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCT ACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTC CTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCG GCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGC TCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGC GCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA AG GAG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatAGAATTGGTGC CCCAGAGGTGGGAAAAACCTACCCTGCTCACTGCTCTATCTCCTGGGCTTAGCTCAGACTCT GGCATACGTGAGTGCTTAGTAGAAACTTGATGGGGTATTAAAATTGAGACCTGGGTGGGTT CTCACATTAAAI 1 IUIAACACTCCTTAGGTGGCTTGGGCCCACCCCTCTGAGCCCTGTTTCCA CATCTGTAAAGTAGCAAACCATCGCCATGAAGAACAGGGAAGAACCAGGTCAGCAGGCAG 2541 132 WO 2022/093846 PCT/US2021/056689 GGCGGATGAAGCATCCAGCCAGTTCTAGGAAGTTTCCGATGGCTAATCCTTCAGATGCAGC TTGTAAGCAGGTCAAATACAGAATAGGAAACTGAGGCGCAACGAAGTCATGCTTAGAAGT CTGTCCAGGGAGACCAGTCAAGGCCTCCCCCACACCCTGCAAGCCCTTCTAGGAGCTCTGG TTAAGTCACTCpARBI- 637: chrll_l_ Exogenou s_99 ATCTTCAAATTGTAGTCTTTGTAACAACCAAATAACCTTTTGTGGTCACTGTAAAATTAATAT TTGGTAGACAGAATCCATGTACCTTTGCTAAGGTTAGAATGAATAATTTATTGTA 1 1 1 1 IAAT TTGAATGTTTGTGC1 1 1 1 1AAATGAGCCAAGACTAGAGGGGAAACTATCACCTAAAATCAGT TTGGAAAACAAGACCTAAAAAGGGAAGGGGATGGGGATTGTGGGGAGAGAGTGGGCGA GGTGCCTTTACTACATGTGTGATCTGAAAACCCTGCTTGGTTCTGAGCTGCGTCTATTGAAT TGGTAAAGTAATACCAATGGCI 1 1 1 1ATCATTTCCTTCTTCCCTTTAAGTTTCACTTGAAATTT TAAAAATCATGGTTAI 1 1 1 1A1CG 1 IGGGAICI 1 ILIGICI ICIGGGI ICCAI Illi IAAATGT TTAAAAATATGTTGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgacc ctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattc tggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtggg ctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGT CCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCG GGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAG AACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1 CGCAACGGGTTTGCCGCCAGA ACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAG GCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACT GCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCC CTTGGAG CCTACCTAG ACTCAG CCG G CTCTCCACG CTTTG CCTG ACCCTG CTTG CTCAACTCT ACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTC TAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGT GCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGA GGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAA GCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCC GCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGT CCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAA GTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATG GCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGAC GGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGC TGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAA GCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGAC GAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatACATGGTAGTTCAGTTCTTA ACCAATGACTTGGGGATGATGCAAACAATTACTGTCGTTGGGATTTAGAGTGTATTAGTCA CGCATGTATGGGGAAGTAGTCTCGGGTATGCTGTTGTGAAATTGAAACTGTAAAAGTAGAT GGTTGAAAGTACTGGTATGTTGCTCTGTATGGTAAGAACTAATTCTGTTACGTCATGTACAT AATTACTAATCACTTTTCTTCCCCTTTACAGCACAAATAAAGTTTGAGTTCTAAACTCATTAG AATTGTTGTATTGCTATGTTACATTTCTCGACCCCTATCACATTGCCTTCATAACGACTTTGG ATGTATCTTCATATTGTAGATTTAGGTCTAGATTTGCTAGCTCCAAGTAATTAAGGCCATGTA GGAGAGCATGGTAACCACAGATAGAACTGGTATTATCCCAAGTGGTCTGCAGACTGC 2541 pARBI- 638: chrll_2_ Exogenou s_97 TTACAGCACAAATAAAGTTTGAGTTCTAAACTCATTAGAATTGTTGTATTGCTATGTTACATT TCTCGACCCCTATCACATTGCCTTCATAACGACTTTGGATGTATCTTCATATTGTAGATTTAG GTCTAGATTTGCTAGCTCCAAGTAATTAAGGCCATGTAGGAGAGCATGGTAACCACAGATA GAACTGGTATTATCCCAAGTGGTCTGCAGACTGCTGAGTGGGGATGGGATCTGCTCTCTGT TGAGAGTTGGTAATCATTGGTTTGAAATGTGATGAAACCACTCAAGCCAATGAAGGTGGGT GTGTAGGTGGGGAGTACTTTGCCATAATATTTTAAAACATTACCTGGTTAGAGTTCTAAGTG GTACTTAI 1 1 1 1GTTTGGTTAGGGGAAAGCCTGAATAAAAACAGAAATGGACACATAATAT GCATATTCCATAGTCTTTtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttcctt gaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattc tattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcgg tgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCAC 2541 133 WO 2022/093846 PCT/US2021/056689 AGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGC GCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGG GAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGC CAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCT GAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGGGAGGCTGGAATGT GCCTGGGATTTGGGTCTAAGTGTATGCGTAATTCTTACCTCACTAAAGAATTTGCCTTGTTTT TTTCCTTTTG GTG AGTG ACTAA AACGTCTG G G CTTCCCTGTGTG CGTG CTACAGTAAG CAAG CAGAGGCTGTGCAAAGGTGTGAGCAGGATCACGTGGAATCTGGAGGATACATCTTGGCTT GCAAACTGCCTCTGTCTCCTGGGTGGGACTGTTCTGTCCTTGCACTGCTGTTCTGTGTTACCT CTTGGGGTGTAAGGTTTTGCTTACAGGAGACAAACTTTGGGCGTAGAATGGAAGCCACTGC CAGCCTCTGTGCTGAGAAGGAAGGTGCTTGTTTCAAAGGGAGCAGCAAGGGAGGCTTGTT CTACTCACCTGGGCCTGTTTGCCTGAGAAGGGGAGATAAGGGCTGAACTGGGACTAGCCA GGGGGApARBI- 639: chrll_3_ Exogenou s_98 TGGGGCTTTGGGGAATTTAGTGCGTGGGTGAGCCAAGAAAATACTAATTAATAATAGTAAG TTGTTAGTGTTGGTTAAGTTGTTGCTTGGAAGTGAGAAGTTGCTTAGAAACTTTCCAAAGTG CTTAGAACTTTAAGTGCAAACAGACAAACTAACAAACAAAAATTGTTTTGCTTTGCTACAAG GTGGGGAAGACTGAAGAAGTGTTAACTGAAAACAGGTGACACAGAGTCACCAGTTTTCCG AGAACCAAAGGGAGGGGTGTGTGATGCCATCTCACAGGCAGGGGAAATGTCTTTACCAGC TTCCTCCTGGTGGCCAAGACAGCCTGTTTCAGAGGGTTGTTTTGTTTGGGGTGTGGGTGTTA TCAAGTGAATTAGTCACTTGAAAGATGGGCGTCAGACTTGCATACGCAGCAGATCAGCATC CTTCGCTGCCCCTTAGCAACTTtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgcc ttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgt cattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggat gcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGG TGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTG GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGC CGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCT ACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTC CTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCG GCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGC TCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGC GCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG 2541 134 WO 2022/093846 PCT/US2021/056689 AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA AG G AG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatAGGTGGTTGATT TGAAACTGTGAAGGTGTGATTTTTTCAGGAGCTGGAAGTCTTAGAAAAGCCTTGTAAATGC CTATATTGTGGGCTTTTAACGTATTTAAGGGACCACTTAAGACGAGATTAGATGGGCTCTTC TGGATTTGTTCCTCATTTGTCACAGGTGTCTTGTGATTGAAAATCATGAGCGAAGTGAAATT GCATTGAATTTCAAGGGAATTTAGTATGTAAATCGTGCCTTAGAAACACATCTGTTGTCTTTT CTGTGTTTGGTCGATATTAATAATGGCAAAAI 1 1 1 1GCCTATCTAGTATCTTCAAATTGTAGT CTTTGTAACAACCAAATAACCTTTTGTGGTCACTGTAAAATTAATATTTGGTAGACAGAATCC ATGTACCTTTGCTAAGGTTAGAATGAATAATTTATTGTAI 1 1 1 1AATTTGAATGTTTGTGCTTTpARBI- 640: chrll_l_ Exogenou s_94 CGACCAACCCATCAAACTCCCCGCCCCCAGCACI UTAH ILICCTCI 1 1AGGAAGTACACTT CAGTATCTTTGGCACAGTGCATGAGCACGACTAAAGTAAAACATCGCAGAAAACATAGCTT TAGTCTACCCTTCGTGTCCTAAAAGGAAAACCAGTAGCTTCCCAGGCCACCGGAAGGGCAA CACATGTCCTCTGCAG1 1 ILIGCACACGGGAAGGTAAAGACAGAGAGAGGACCTACTCCTC AACACAGAAACATTTCAAAATCTTTCCTCGCCTGCAACCCAAGCTGAAGTCATTCTCCCCAG AAATAACAAAAGTTGGAAGAGAAGCCGGAGACAGGATAGGTGCAGGAAGCCCACACTTTG AGGGCAGCACTCAGACACCCTCTCCTGTGTGCAGGACGTGCCGAATGTTCAGGTGCAATGA GAATGAGCCATGCTTGGCTTAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgcc ttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgt cattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggat gcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGG TGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTG GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGC CGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCT ACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTC CTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCG GCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGC TCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGC GCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA AG GAG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCGAGGGCAATC TG G CCCATCAAGTG G CCTTCG CCTCTG G G AGTAACA AAAATG CACTTCAAAATAG CTTCTGT AATCAAGCTGCATGGGTGGAGTACTCCCCAGCTGACTCCAGGAAGTTCTCTATCCAAAGCT ATTCATTAGGCCAGAGCTGTGCAAATAATTAGTCACCCACTTGCTCCATAACCCTCCATGAC AGCCCAGGCATTGAGTCCAGGTGGGACCATCAAGCCATGCTCTGGTGGCTCATGCATTATC ATAGAAATGGGAGGCTTTATTTATTTTACTAAAAAGAACAAAAACAACAGACTGCTGTCCTT TAGACAATAGGATCACGTCATCTGAGCCCTCTGTGCCCCAGGTGACAAGCCCAGCCCCAAG 2541 135 WO 2022/093846 PCT/US2021/056689 TTCTCTTTCCTCAGCCTCCCCACACATGTTCTGGAGGAGATGGGCCCAGCAGGCTGCTCTGA GGCCTGGCpARBI- 641: chrll_2_ Exogenou s_96 TCACAGAATCTTGTTTGAGCTAACAACCAGTTATTCTACCCAAAGTAAAGAGTAACTTAAAT TTTCCCATTGTTCTTCCAGGCTGGAAGATGTAAGAAACACACACAGTATAGTGTAGGTTTCC TCCATAGTTAAGTACCCCAGAGCTAGGCTGAAATCCAGTGTTGGATTGTTTCCAACTTATAG TAGGGAACCGCCAATGACATGAAAGAGCATTACCTTACCGGACTGATTCATATTCTACTTCC AGTCATAGTACAAATGATCACATGTCCACACCCACATGTGCTCTGATAAGTAGTCAATTGAG AGGAGTGAGTCAGGGAGCCGTAACTTTGCAGCCAACCTGCCAAGAAGAACTGATGCTTTTA GAAATTCAGCAGCTTTCATTGGCATAGAAGTTTCAGCCTTATAGGCCCAGGG 1 1 ILICTGAG GCAGAGGCAAACCCTGTtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttcctt gaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattc tattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcgg tgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCAC AGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGC GCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGG GAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGC CAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCT GAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTGTTATGTTGTTATCT CAGGAI 1 LI 1 1 1 1 1 1 1 1 1 1 1 1 1GAGACAGAGTCTCACTCTGTTGCCCAGGCTGGAGTGCAGTG GCACAATCTCGGCTCACTGCAAGCTCCGCCTCCCGGGTTCACGCCATTCTCCTGCCTCAGCC TCCCGAGTAGCTGGGACTACAGGCGCCCGCCACCACGCCI 1 1 LI AAAI 1 1 1G1A1 1 1 1 IAGT AGAGACGGGATTTCACCATGTTAGCCAGGATGGTCTCGATCTCCTGACCTCGTGATCCGCC GCCCTGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACTGCGCCCAGCCTATCTCAG GATTCTTAATGTAAAAACAGTTCAGTATGGAAAGCGTACTTATGACAGAGCTGTTGCAGAA TGTGAAATCACCCATGTGCCTAAGTGTCTCCCTACTACCTGGAACACTAGACCACATGCAGC AG 2541 pARBI- 642: chrll_3_ Exogenou s_95 CAGCCCTGAACTCAGCCTTCACGGCCCTCCCTAAACACATGGGCCAGCCACAGGGAAGAAA AAAATGCCCTGTAGCACAGGAATCTAAAACATTGCTGTTGTTCTAGTTAATAAAAGGACTTA GAGATTGAAAAGAAGTACCATCTGTATGGCTGGCAACAGACAGCATGATTTTGATGACTGA CTCTGGGGAGATCTGAGAAAACAGTACATAATATGTCCTTACCTCTGCTCCATCATTCATGA CCCAAGCTCCTGCCCTGTCTTCTCAGGAAGATTCTTACAGTAACTCCAGTTTGGAATTCCCCT TTCATATTTGAAATAACAACAGTAATAGTGACCACTAATGCTTACCGAGTGTCCACTCTGTG CCAAGCATCGTG 1 1 1 1 1 Al GAI LI 1 1 1 1 1 GTTAGGCACTGTACATGGATTAATACAATTACAA CCCACCACAACCCCATtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttga ccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctat tctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgg gctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAG TCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGC 2541 136 WO 2022/093846 PCT/US2021/056689 GGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGA GAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCA GAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTG AGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAA CTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCT CCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACT CTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTAC TCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTG GTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGC GAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGC AAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCA GCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTA CGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTG AAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAG G ACG G CAACATCCTG G G G CAC AAG CTG G AGTACAACTACAAC AG CCAC AACGTCTATATCA TGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGG ACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGT GCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAG AAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGG ACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaat aaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGAGATAAGTACTTGTACT ATCCTCATTTTATGGGTGATGATACAAGAAACAGAAAGGTTCAGCAACATGCCTAAAGCCA CACAGCTACTATGAGGCAAAGTCTAGGTTTGAACTCAGAAATTCTGACTTCAGACTCACTTA TCTTATTATACTTCACTTAGTATCTCCCATTAATTAATTCATTCATTCTTCCTTTTATTTGTTAAT TCACCAAATATTCTGGGAAGCTACTTGTCTAGACACTGTATGAAAAATGAGAATGGATACA AAGCAACCTCAGACATGAACTCAAGGTCCTTACAAGCTTAAACGTATATGATACATTTCCAA ATAGCAATACTATGAGGACAGCTGATACTCACAACATAAGTCTTGGTGGTCACAGGAGATC TATCATAGGATTTCACGAAGAACCTGACACTGAAAACCAGAACTTGAGGGAAATAAAACpARBI- 643: chrl5_l_ Exogenou s_100 GTGTCCATCCTGCATGTCTCAAGTCACAATCCTCCAGATATTCAACCAAAGTGCTTGATTCTG TTGGCACAAGGACCATGAAATCTTCAGTAGCTAAGGAGACTCTTTGACAAATAGATTTATTG CATATGATGTAAAAGGGTCTCATTCAGAGAACTACACATTTACTACACATTTACTAGCTGTT AGATGTGAGAAATTGAAGCTTTGAGAATTGTCATTTTGTAAGCACGCTGTAATAATTGTGTT CTCTACAAAAATGGAGAAATACTTAATCTTTGCAGG 1 1 1 1 1ATTAGCTTCGAAAAAGGGAAT ACAAATATTTTGATACCTGACTTTATTTTAAAGATACTGGCAAGCAAGGAAAGATACTCAGT TTGCTAAATTATAGCATAGATTTGAAAGACGGAAATTTTTTTTTGTTATTTTGATTCTTTCTGA TTCAGAACCTGCGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccc tggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattct ggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggc tctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTC CCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGG GGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGA ACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1 CGCAACGGGTTTGCCGCCAGAA CACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGG CCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTG CGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCC TTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTA CGTCTTTGTTTCGTTTICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCT AGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGT GCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGA GGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAA GCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCC GCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGT CCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAA GTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATG 2541 137 WO 2022/093846 PCT/US2021/056689 GCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGAC GGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGC TGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAA GCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGAC GAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTGAGTTTCCATTCCTGGGAT AGAGAGCCCTGCCAAAGCCAACTCAGTCTCCTGTTATTGCAGAAATTTAAAGGTTACTTGAG CTGATTGATACCAATTAAAATAAAAGCATCTACTGCCATTTTATTAAACGCCCTATTTAATCT CC ACATCCCAAGTTCATTCTCTCTCTCTTTTAAG G CTATACATG G G CCTC AACATTCTCTCTTC TTCAGTATCAGCTGTCCTCATCCCTATTCAAAGTCAGAATGACTTGGAATCTATTCAGGGCT GCTACTTAATTGGATGAAGAAAGTACTCTGTTGCATGCTAACCTCCCAGATTTGAATTAGAA CCAAGGTCCTGAATCTACACAAGACCI 1 1 1 ICCCI 1 ICCI 1 ILIGCAI 1 1 Al 1 ILI 1 1 1 1 1 1 ICT ACATCTTTCI 1 1 1 IGAAI 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1L1GAGATAGAGTCTTGpARBI- 644: chrl5_2_ Exogenou s_101 ATCATCAAAATCTTCATTTATACAAATCACGGGTATTAGAAATAAAATCAGGTATTGTGTAC AGTCAGATCCCAGGTTTACACAAACTAGAGGTTTCAATTAAGTTTCCTTCATTTTATAAAACC ATGACACAAGCTGTAAATAAAGGAGCTCTGGCTTTAGGCCTTCTTCTGTTTATAGACAGTAA ATTTTAATCCTCTGTCCCTGCAGACCAACTCAAAGCAGTAACCTTGGCTACCGTTGCCGCAG AAGAAACACACCCTGCAGATTTCCAGTTCTATATTCAGTCTTAGAAAATTGGTCATGTTGAA AGGGAAAAAACAATTTTACTTTGCCTCAGTTATTGACACCAAGAAGCACTCCTCAGCCTGTT CAGAGGGGAAACAATGAGTCATTCATGCTGTCAGCCCAGGTGGTGCATGAATTCCAGACA GAGGCCGCTGAATTAACtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttcctt gaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattc tattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcgg tgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCAC AGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGC GCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGG GAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGC CAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCT GAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCCGTGGAGGCGTCTC TCTGAGCAGAGCCCGCAATGCGCCTGCTTGGGGCTCCCTGCAGCCTCTGGGGGAGGCAGG GCGGCCCAGAGCAGGCCTGTGCTGGAAAGGAACGCGAAGCCCTGTAACCAAGCCTGTACC TCTGCAGTGCTAGTCCCAAGGGGCCTCCGAGCTGTTTGTCACCATGTGATTGGCTCAGGAG AGGGGTGGAGAAATGAAAACACTCTGCCCAGGATATATTTAGTTGAAGTGCAGCTGGGGA AGTGCTTAAACAAGGGAGCTTTTGTCCTTATGTTGAAGTG Hill CTTAACTCCTCAAGGGT GAAAAACTTGAGCCACGTACTGATCCCATTCCCCCCCACCACCCCCAATATATIIICTCTTCT TTAGGAAATGCTCTTATTCTGAAACTTTAGAATIIICTAGGGTTTGTTGCATAAGAGGAAAC TGAATAA 2541 138 WO 2022/093846 PCT/US2021/056689 pARBI- 645: chrl5_3_ Exogenou s_102 CTTTCCI 1 ICTGCAI 1 1A1 1 ILI 1 1 1 1 1 1 ILIACATCI 1 ICI 1 1 1 IGAAI 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 CTGAGATAGAGTCTTGCTCTGTCGCCAGGCTGGAGTGCAGTGGTGTGATCTTGGCTCACTG CAGTCTCCAACTCTGGTTCAAGCAATTCTCCTGCCTCAGCCTCCGGGTAGCTGGGACTACAG GCATACACCACCATGCCCAGCTAAI 1 1 1 IGIAI1 1 1 1AGTAGAGATGGGGTTTCACCATAGT GGCCAGGATGGTCTCCATCTCTTGACCTCGTGACCTGACCCCCTCGGCCTCCCAAAGTGCTG AGATTACAGGCATGAGCCACCGCGCCCGGCCTCI 1 1 1 IGAAI Hill 1AAAAAAACACCTAA AGTTTAGGAAAGTATAAGAGGCCAAAGAAACAAGAGTTCAAAGAAACAAGAGTGTTATAC ACGCACACTTGCAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccc tggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattct ggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggc tctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTC CCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGG GGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGA ACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCAGAA CACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGG CCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTG CGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCC TTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTA CGTCTTTGTTTCGTTTICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCT AGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGT GCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGA GGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAA GCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCC GCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGT CCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAA GTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATG GCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGAC GGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGC TGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAA GCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGAC GAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGAAAGGTAGTAAAATATCT GTATAGTTCTGGCTGTCAAGCTTTTGGACTGAGATATGCGTAAGCAAGGCAAAAAGATCCC ATAGTCCAGGAATATCAACCAGTCCAGTTTCCCAAGGAAACTAAAAGTAACTGAAAATGAG AAG G GTG CCATATAG G A AAATTG AAG GTG G G G CATAATTATTAATACACTG CTTTG G AAAT G CTG GTATG G AAG ATTCATATATG G ACTTCAAAG CATAC ATGTCTTATACTTAG CTATG G G A AAATTATCATCAAAATCTTCATTTATACAAATC ACG G GTATTAG AAATAAAATCAG GTATTG TGTACAGTCAGATCCCAGGTTTACACAAACTAGAGGTTTCAATTAAGTTTCCTTCATTTTATA AAACCATGACACAAGCTGTAAATAAAGGAGCTCTGGCTTTAGGCCTTCTTCTGTTTATAGA 2541 pARBI- 646: chrl6_l_ Exogenou s_103 TGTCTTCACGGCACGGCCCCCGCTTCACCAGCTGCACTGTTTGATGAGCTTTGCAGGTCCCA GATCTTATAAG CTCATG GTG ATTGATCCAAATGATG CAGAGGTCGG CCTAAAGTTAG AAGT GGGCCCCTCTCTGCCCCAAGACAGCCCTTCACCCCAATTCCATTCCCACAGTTTGGGCATCC ACCCAGGCTGCCAAGCCAAGCGGGGGCTGCCCGGGTTAGCAGGGACCTGGCCATGGGCCT CCTCAGCTAGGGGCCGCCTCTCTGAGGAGTGGGTGCCCCGCCCCTCCGTGGGCCGCCTGGT TTCTCTTATTG G CAG CGTCTGTAGTCCCCTG G CTCTGTCACCCG CAG CTATTCTAG G CCTCTG GTTCCTTTCACI 1 ILIGCTCTGCGTCTTCCTGCCTCGGTGGTTCCCCACCATCCAGCCTGAGA CCTCCCCGTTGCCCGCCCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttcct tgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcatt ctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcg gtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCA CAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGG CGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGG GGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1 CGCAACGGGTTTGCCG CCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACC 2541 139 WO 2022/093846 PCT/US2021/056689 TGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTGGGTTTCTGTCTGCT CCTCTCCGTG GTG G CCG G CCCTG G CTCTG CCCCAAAG CCATG G AG AAG G CCAAATG CAG G C TGTAGAAAGGTCTGGGATCAGATCCCCCCATCCTTCCATGGCCACGTGACCGGGCCCGCCT CTTCCCTCTGAGCCTCACATCCTCATCTGAAGAGGGAATGCTGCTCATGCCCACCTTGCGGG GATGTGGGGAGGGGGTGCTGCCAGTGGAGACTCCCAGGGGACCCTCCAGGAGTCTCATCC TGACTCGAGACTGGGCACCTGGTGGGGGCACAGGCCCCCTCTCCCGCCATGGGACCGCCA CATCCAGGCTCTCGTGGGTTGAGATGCTGAGGAAAGGAAAGAACAAAACCTGCTGGAGGA GCAGCGAACACGGCCCTCAGCTGGGTGACCTTGGGCAAGTCACTTCCCCTCTCTGGGCCTC AGTTTCCATpARBI- 647: chrl6_2_ Exogenou s_104 CTGAAGAGGGAATGCTGCTCATGCCCACCTTGCGGGGATGTGGGGAGGGGGTGCTGCCAG TGGAGACTCCCAGGGGACCCTCCAGGAGTCTCATCCTGACTCGAGACTGGGCACCTGGTGG GGGCACAGGCCCCCTCTCCCGCCATGGGACCGCCACATCCAGGCTCTCGTGGGTTGAGATG CTGAGGAAAGGAAAGAACAAAACCTGCTGGAGGAGCAGCGAACACGGCCCTCAGCTGGG TGACCTTGGGCAAGTCACTTCCCCTCTCTGGGCCTCAGTTTCCATATCTGTGAATGAGGCAG CTGGACTGAAGAATAGAGAGTCACAAAGCAGAGTGACACAAACTGGGCTACAGGAAACCC TGGAGGCCCTCGACCCAGGCTGGGGCCGGGGATGGTTCTGCAAAGCCTCTTGGGAGAGGG TTGCCTGAGCTGAGTCTCCAAACAGAAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcc cccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctga gtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatg ctggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCA CATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGA GAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGA GGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGG GTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGC CGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGG TGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTT GTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTG CTTGCTCAACTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGA CCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGT TCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCA GCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCT GCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGT GCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGC CCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCG CGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGA CTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAA CGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCAC AACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGC 2541 140 WO 2022/093846 PCT/US2021/056689 GACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAG ACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCAC TCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatc acaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCAGTGG CCTTAAGTCACGGGAGATGAGCCAGAGCAGTCCAGAGGGCACGGTCAGCACATGCTAAGG TCCTGGGGCACAGAGTACAGGGCTTGAGAAGGGTTCCTCTTGCTCCATGTGACTTTCATCAT CCAACAGCCTGTGGTGGCACTTGCCTGTATCCCAGCTATCTAGGAGGCTGAGGTGGGAGG ATTGCTTGAGTCTGAGAGGTCGGGCTTGTTCTCCCGGTGTTGGCAGAGTCCAGAGGGAGCA AGTGGAAGCCACAGGTGTCTTGAGGCCTAGGCTGAGATCTAGCACATCACCGCGTCACTTC ATCCCTTCATTTCATCCTATTGGCCAAAGCAGCCCAATTCTAGGGATGGGGATCTAGACTCA ACTTCTTGATGGGAGAAGTAGCAAAGTCACACTGCCAAGGGCAGGGACACAGGGAGGGAT GAAGAGTTAGGAATGGTTpARBI- 648: chrl6_3_ Exogenou s_105 AAGCCACCTCCCTGCTCTGTTGCTGGCTCTCCTTGAAGACAAGTG 1 1 1 1 1CAATTAACCAAAG CGGTGCATGGCAATGTGATAGGGGAATGAAACACAGCAACAGAATCAATGCCCCACGCTG GGCAATAGCCGACI 1 ILIGTTCGCTCCCATCCCTTCCTTCCCTCCCCGCCTCCTTCCCCTGCTC CTTCCATTCCACAAACATTTATTGAGCACCCGCTGTGTGCCAGCCACTGTTCTAGGCCCTGA AGACACAGAAGTGAACAAAAAAAAAGAGTCCCTGTGCACATCCTGGAGGGACTTTCCCCGT GTGTGTGTGTGTGTGTGTGTGTGTGTGTCTATACAGTGTATGGAGACAGTGGATAATAAAA GCTGTTTATGAGGCACI 1 ILICTGAGCTGTTCCATGTGCTTCACTTATACTCATTCAGCTAAT CCTCAGGACACCCCCGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttg accctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattct attctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggt gggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCAC AGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGC GCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGG GAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGC CAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCT GAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTGAAGTCAGTGATATT AGTCACAGAGGCCCAGAGAAGTGAAGTGACTTGCCCAAGGTCACACAGCCAGCAAGAGGC CAAGCCCGGATTGAACCCCAGCCGCCTGGCTCTGGAGCCTGCAGCATAACCACAGCAGGG AACTGCCACCGGAGACAGACATCGACAGCCACTAGGAGATGTTAACCAACAGGCTTGTCTT CACGGCACGGCCCCCGCTTCACCAGCTGCACTGTTTGATGAGCTTTGCAGGTCCCAGATCTT ATAAGCTCATGGTGATTGATCCAAATGATGCAGAGGTCGGCCTAAAGTTAGAAGTGGGCCC CTCTCTGCCCCAAGACAGCCCTTCACCCCAATTCCATTCCCACAGTTTGGGCATCCACCCAGG CTGCCAAGCCAAGCGGGGGCTGCCCGGGTTAGCAGGGACCTGGCCATGGGCCTCCTCAGC TAGGGGC 2541 pARBI- 649:GGGGGCGGCCGCACGGCTAGAGCGGAGACCCCGCGCCCCCTCCGCCCGCGTGGCCCGGCC GGGGTGCGGGGCCCGGGGAGGCACGGGGGCTGCGCGTCGGGGCGCAGCCGCCGCCCGC2541 141 WO 2022/093846 PCT/US2021/056689 EDF1_1_E xogenous _25 GTGTGCTCGGAGGCCGCGGGGCCCGGGCTCCGGGGTCCTCCCGACCTGCAGCCCCAGCGG CTACCGCGCCTCGCCAGGCCAGGCCAGGCCCCGACGTCGCCTTCCCTACGTCGCCGGCGCC CGGCCACGACGTCCCTCAGACGAGCCGAACGCCGAATGGCCCCGAGCACGGGAAGTGCCC GCCCCCCGCGTGCAGCCAGCCAATGGGACGCCGAAAGCGGGGAGGTGCCGAGGGGACGT AGCGTCGCCGCGCCAGGTCTCTAGCAGCTGCCGCTGAGCCGCCGGACGGACGCTCGTCTTC GCCCGCCATGGCCGAGAGCGACTGGGACACGtgacgactgtgccttctagttgccagccatctgttgtttg cccctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcat tgtctgagtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagc aggcatgctggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGA GCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTG CCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCTTT TTCCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICG CAACGGGTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGC GCCCGCCGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGC CTGTGGTGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCG GGCCTTTGTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCT GACCCTGCTTGCTCAACTCTACGTCTTTGTTTCGTTITCTGTTCTGCGCCGTTACAGATCCAA GCTGTGACCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAG GAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCAC AAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAG TTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTA CGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCC GCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACA AGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGG GCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACA GCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGAT CCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCC ATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGA GCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCG GGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagc aatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatctta tGTGACGGTGCTGCGCAAGAAGGGCCCTACGGCCGCCCAGGCCAAATCCAAGCAGGTGCTT TGCTGACTGAGGAGCGGCCGGGCCGGGCGGGGCGGACGCTgggccggggccacggaccgtgggg cagggggctcggggaagggcaggcggggcctgggacagggcgcaggggacggggacaaggctggGGTGCCGG GGGCAGGACGGGGTTCGAAGGGCGGGGCGAATCGCAGGGGTAGGAGGACCGGGCCAGG ACaggggtgggaaggtggggggcggacccaggaggggatggacggacccaggaggcagggggCGGGCGACTG GAGGAGGAGAGGAGCAGGGAACCGGACGGGGCAAGGGGCAGGCGATAGGGCCGGGAC CAGTGCCAGGGTGGGGCGGGGAGGGGATAGGGGCAGGGACTGTTGGTGGGGACAGGTG TGAGGACAGpARBI- 650:EDF1_2_E xogenous _26 ACGGCTAGAGCGGAGACCCCGCGCCCCCTCCGCCCGCGTGGCCCGGCCGGGGTGCGGGGC CCGGGGAGGCACGGGGGCTGCGCGTCGGGGCGCAGCCGCCGCCCGCGTGTGCTCGGAGG CCGCGGGGCCCGGGCTCCGGGGTCCTCCCGACCTGCAGCCCCAGCGGCTACCGCGCCTCGC CAGGCCAGGCCAGGCCCCGACGTCGCCTTCCCTACGTCGCCGGCGCCCGGCCACGACGTCC CTCAGACGAGCCGAACGCCGAATGGCCCCGAGCACGGGAAGTGCCCGCCCCCCGCGTGCA GCCAGCCAATGGGACGCCGAAAGCGGGGAGGTGCCGAGGGGACGTAGCGTCGCCGCGCC AGGTCTCTAGCAGCTGCCGCTGAGCCGCCGGACGGACGCTCGTCTTCGCCCGCCATGGCCG AGAGCGACTGGGACACGGTGACGGTGCTGtgacgactgtgccttctagttgccagccatctgttgtttgccc ctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgt ctgagtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcagg catgctggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGC GCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCT AGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 IC CCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAA CGGGTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCC CGCCGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTG 2541 142 WO 2022/093846 PCT/US2021/056689 TGGTGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGC CTTTGTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGAC CCTGCTTGCTCAACTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCT GTGACCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAG CTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAG TTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTC ATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGG CGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCA TGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGAC CCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCAT CGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCA CAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGC CACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCG GCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAA AGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGAT CACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatag catcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCGC AAGAAGGGCCCTACGGCCGCCCAGGCCAAATCCAAGCAGGTGCTTTGCTGACTGAGGAGC GGCCGGGCCGGGCGGGGCGGACGCTgggccggggccacggaccgtggggcagggggctcggggaaggg caggcggggcctgggacagggcgcaggggacggggacaaggctggGGTGCCGGGGGCAGGACGGGGTT CGAAGGGCGGGGCGAATCGCAGGGGTAGGAGGACCGGGCCAGGACaggggtgggaaggtggg gggcggacccaggaggggatggacggacccaggaggcagggggCGGGCGACTGGAGGAGGAGAGGAG CAGGGAACCGGACGGGGCAAGGGGCAGGCGATAGGGCCGGGACCAGTGCCAGGGTGGG GCGGGGAGGGGATAGGGGCAGGGACTGTTGGTGGGGACAGGTGTGAGGACAGAGGCAG GAGGTGpARBI- 651: EDF1_3_E xogenous CCCTGG AGTCG GTGTG AG GCAAAAG CAG AG G AG AG G ATTTG G AATTAACCTG AAG AAAAA CCATTTCAAAGCGGTAACCAGACCCCAGAGGCTGCCTGAACTCAAGGGGACATGGGAACC CAGGCTGTCCCAAGTTCACACACCTCAGGTCGTGGACTTCCAGAG1 1 1 1L1L1CAGTTATGA GGACAGGCAGCTGTACTCATGCCAACCAGAGCTGCTCTGGGAAGATGGCTGCCTCCCAGG GCTCCGGCCAGCACCGGTGCAGGCAGGCACTCAGCTGACAACGTCCCCGGGGGCGCCGCA CACACCACACCCACCAGCACATGGACCCCACAGCACAGCCTCATGTTGCAAGCGGAAACAC AAGTACCTACATTTCTTGGAAGTCTCCACATCTTCTCCTCGTCTCTGTGCCGCTAAGATAGCC TAGAAAATTAGAAAACATCAGTGGtgacgactgtgccttctagttgccagccatctgttgtttgcccctccccc gtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagta ggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctg gggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACA TCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAG AAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAG GGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGGGT TTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTG CCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGT CCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCT TGCTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACC GGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTC ACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGC GTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGC ACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGC AGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCC GAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCG CCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACT TCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACG TCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAA CATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGA CGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGAC 2541 143 WO 2022/093846 PCT/US2021/056689 CCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTC TCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcaca aatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTTTCTAAAG AGAAGATGTGCTTTATACACATCAGCTCCACTAGGACTGCTGCAAAACCAGGCGCGAAGCG TCG CCTG AG AACAG CAG CTTCTAG G G CCCCTG G G GTACG CACCCACACG CAG CTG G GTTTT GTGCGAGAGGCAGTGAGAGCCGGGCTGACCTGGCTTCCCGAGGCATTCCCTGCAGGGGAA CCAGGGGGGTGGAGCCCACCCTCCCCGTGCTATCTGAACACCGGCCATCCCCCTCCCCAAA CCCACAACCCCAGGAGTGAGAGCCCCGGCGCAGCCTCACCGTGGCCAGGTCCTTCTGCGTA AGCCCCTTGCTCTGCCGACCTTGCTGGATCACCTTGCCCACCTCCAGGGTCACCCTGTCATG GTGCAGCTCCTCTGTCTCCCGGTCCAGCTTGGCCGTGTTCTTGGTAATAGAATGTTGTTTGTT CTGGCCAGCAGCpARBI- 652: FTL_l_Ex ogenous_ 30 CTCTTGCTTCAACAGTGTTTGGACGGAACAGATCCGGGGACTCTCTTCCAGCCTCCGACCGC CCTCCGATTTCCTCTCCGCTTGCAACCTCCGGGACCATCTTCTCGGCCATCTCCTGCTTCTGG GACCTGCCAGCACCG 1 1 1 1 1GTGGTTAGCTCCTTCTTGCCAACCAACCATGAGCTCCCAGATT CGTCAGAATTATTCCACCGACGTGGAGGCAGCCGTCAACAGCCTGGTCAATTTGTACCTGC AGG CCTCCTACACCTACCTCTCTCTG GTG AGTCCCCAG G ACGCCCCTG GCCCTAATTTCCTCC AGCTGCGCACCTCCGGCCCTCACTGCACGCGCCAGCCTTCTTTGTGCGGTCGGGTAAACAG AGGGCGGAGTCCCCTTGGCCTCGCCTCCCGCTAACCATTGTTGCCTCCATCTCTTCCCGTAG GGCTTCTATTTCGACtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgac cctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctatt ctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgg gctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAG TCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGC GGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGA GAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCA GAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTG AGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAA CTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCT CCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACT CTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTAC TCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTG GTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGC GAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGC AAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCA GCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTA CGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTG AAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAG G ACG G CAACATCCTG G G G CAC AAG CTG G AGTACAACTACAAC AG CCAC AACGTCTATATCA TGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGG ACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGT GCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAG AAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGG ACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaat aaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCGCGATGATGTGGCTCTG GAAGGCGTGAGCCACTTCTTCCGCGAATTGGCCGAGGAGAAGCGCGAGGGCTACGAGCGT CTCCTGAAGATGCAAAACCAGCGTGGCGGCCGCGCTCTCTTCCAGGACATCAAGGTAACTA GTGTGTGGGTAATGGACTACATCTCCCAGCAGGCCGTGCGCGCGAGGAGCCTTGATTTGA GGGCGTAGGTGTCGCGTGGGCTTCTGGGAGATTGAGTTCGGTCTTGTGAGCCCTCTTAACC GCTGGAAATAGAGGCGCACCTCGTGCAGTGCCCACAACACGCGGCAGTCCACACCGCTGC GTGGTCTTAGGGACGTATAGCTGTAAGAGCTAGGACAGGGTGCGGAGAGTGATAAATACA AGCTGTCACATGTCTTTGTGGCCTGGGCCTCTGACCCCCAACGACTCTTGGGAAATGTAGGT TTAGTTCT 2541 pARBI- 653: FTL_2_Ex TGGGGCGGGGGGCTGAGACTCCTATGTGCTCCGGATTGGTCAGGCACGGCCTTCGGCCCC GCCTCCTGCCACCGCAGATTGGCCGCTAGCCCTCCCCGAGCGCCCTGCCTCCGAGGGCCGG CGCACCATAAAAGAAGCCGCCCTAGCCACGTCCCCTCGCAGTTCGGCGGTCCCGCGGGTCT 2541 144 WO 2022/093846 PCT/US2021/056689 ogenous_GTCTCTTGCTTCAACAGTGTTTGGACGGAACAGATCCGGGGACTCTCTTCCAGCCTCCGACC GCCCTCCGATTTCCTCTCCGCTTGCAACCTCCGGGACCATCTTCTCGGCCATCTCCTGCTTCT GGGACCTGCCAGCACCG1 1 1 1 1GTGGTTAGCTCCTTCTTGCCAACCAACCATGAGCTCCCAG ATTCGTCAGAATTATTCCACCGACGTGGAGGCAGCCGTCAACAGCCTGGTCAATTTGTACCT GCAGGCCTCCTACACCTACtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttc cttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtca ttctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgc ggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCC ACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTG GCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTGG GGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCC GCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTA CCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCC TGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGG CGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTC AACTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGC CTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGG GGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTC CGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCAC CGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGC TTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAG GCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGA GGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAA GGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTA TATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATC GAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGC CCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCA ACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGG CATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaattt cacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCTCTCTCTGGTGA GTCCCCAGGACGCCCCTGGCCCTAATTTCCTCCAGCTGCGCACCTCCGGCCCTCACTGCACG CGCCAGCCTTCTTTGTGCGGTCGGGTAAACAGAGGGCGGAGTCCCCTTGGCCTCGCCTCCC GCTAACCATTGTTGCCTCCATCTCTTCCCGTAGGGCTTCTATTTCGACCGCGATGATGTGGCT CTGGAAGGCGTGAGCCACTTCTTCCGCGAATTGGCCGAGGAGAAGCGCGAGGGCTACGAG CGTCTCCTGAAGATGCAAAACCAGCGTGGCGGCCGCGCTCTCTTCCAGGACATCAAGGTAA CTAGTGTGTGGGTAATGGACTACATCTCCCAGCAGGCCGTGCGCGCGAGGAGCCTTGATTT GAGGGCGTAGGTGTCGCGTGGGCTTCTGGGAGATTGAGTTCGGTCTTGTGAGCCCTCTTAA CCGCTGGApARBI- 654: PTEN_1_ Exogenou s_31 CTTTGCATAGTTTATCCTATTAGTAATCTATTCTGTCTTTGGAATATGTTTTGTGATGATGAA ATAAATACTATAAATAGTATTATTCCTTTTGCATTGAGAGTCCTGACGAAATGTCCATGTGA CAGTTCATTTTGGGTTTAGCTCTACCTCTAATATGTGACCTATGCTACCAGTCCGTATAGCGT AAATTCCCAGAATATATCCTCCTGAATAAAATGGGGGAAAATAATACCTGGCTTCCTTAATG ATTATATTTAAGACTTATCAAGAGACTATTTTCTATTTAACAATTAGAAAGTTAAGCAATACA TTA1 1 1 1 ICICIGGAAICCAGIGI 1 ICI 1 1 IAAAIACCIGI IAAGI 1 IGIAIGCAACAI 1 ILIA AAGTTACCTACTTGTTAATTAAAAATTCAAGAG IIIIIIIIILIIAIILI GAGG 1 1A1C1 1 1 1 ACCACAGTTtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaa ggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggg gtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctatg gGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCG AGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGGT AAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACC GTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGGGTTTGCCGCCAGAACAC AGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCG CCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGT CCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTG 2541 145 WO 2022/093846 PCT/US2021/056689 2541 GAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGT CTTTGTTTCGTTIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGA GCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCC ATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGC GAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGC CCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTAC CCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGG AGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGA GGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAA CATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGAC AAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGC GTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGC CCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCG ATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCT GTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattt ttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGCACAATATCCTTTTGAAGACCATA ACCCACCACAGCTAGAACTTATCAAACCCTTTTGTGAAGATCTTGACCAATGGCTAAGTGAA GATGACAATCATGTTGCAGCAATTCACTGTAAAGCTGGAAAGGGACGAACTGGTGTAATGA TATGTGCATATTTATTACATCGGGGCAAAI 1 1 1 1AAAGGCACAAGAGGCCCIAGAI 1 ILIAT GGGGAAGTAAGGACCAGAGACAAAAAGGTAAGTTAI 1 1 1 11 GAIG11 1 1 1CCTTTCCTCTTC CTGGATCTGAGAATTTATTGGAAAACAGATTTTGGGTTTCTTTTTTTCCTTCAGTTTTATTGA GGTGTAATTGACAAGTAAAAATTATATATAAATACAATGTATAATATGATGTTTTGATGTAT GTGTATATACATTGTGAAATGATTACTACAGTCAAACTACTTAACATATTCATpARBI- 655: PTEN_2_ Exogenou s_32 GCTACCAGTCCGTATAGCGTAAATTCCCAGAATATATCCTCCTGAATAAAATGGGGGAAAA TAATACCTGGCTTCCTTAATGATTATATTTAAGACTTATCAAGAGACTATTTTCTATTTAACA ATTAGAAAGTTAAGCAATACATTAI 1 1 1 1CTCTGGAATCCAGTGTTTCTTTTAAATACCTGTT AAGTTTGTATGCAACATTTCTAAAGTTACCTACTTGTTAATTAAAAATTCAAGAG 1 1 1 1 1 1 1 1 CTTATTCTGAGGTTATCI 1 1 1 1ACCACAGTTGCACAATATCCTTTTGAAGACCATAACCCACC ACAGCTAGAACTTATCAAACCCTTTTGTGAAGATCTTGACCAATGGCTAAGTGAAGATGACA ATCATGTTGCAGCAATTCACTGTAAAGCTGGAAAGGGACGAACTGGTGTAATGATATGTGC ATATTTATTACATtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccct ggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctg gggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggct ctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTC CCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGG GGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGA ACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1 CGCAACGGGTTTGCCGCCAGAA CACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGG CCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTG CGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCC TTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTA CGTCTTTGTTTCGTTTICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCT AGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGT GCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGA GGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAA GCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCC GCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGT CCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAA GTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATG GCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGAC GGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGC TGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAA GCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGAC GAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa 146 WO 2022/093846 PCT/US2021/056689 agcalllltltcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCGGGGCAAAI 1 1 1 1AAAGG CACAAGAGGCCCTAGAI 1 ILIATGGGGAAGTAAGGACCAGAGACAAAAAGGTAAGTTATT TTTTGATG Hill CCTTTCCTCTTCCTGGATCTGAGAATTTATTGGAAAACAGATTTTGGGTTT Cl 1 1 1 1 1 1CCTTCAGTTTTATTGAGGTGTAATTGACAAGTAAAAATTATATATAAATACAATG TATAATATGATGTTTTGATGTATGTGTATATACATTGTGAAATGATTACTACAGTCAAACTAC TTAACATATTCATCACCTCACATAATTATTATTCTCCCCCCAGGGTGAAAGCATTTAAGATCT ACAAGCTACAATTTTCAATTATACAATGTTATTATTAACTATAGTCACTATGCTGTCCAGTAG AGCTTCAGATCTTGTTCATCTTGTGTTCCTCCCTCCCCACCCTCAGTCCCTGGAApARBI- 656: PTEN_3_ Exogenou s_33 ATAAATAGTATTATTCCTTTTGCATTGAGAGTCCTGACGAAATGTCCATGTGACAGTTCATTT TGGGTTTAGCTCTACCTCTAATATGTGACCTATGCTACCAGTCCGTATAGCGTAAATTCCCA GAATATATCCTCCTGAATAAAATGGGGGAAAATAATACCTGGCTTCCTTAATGATTATATTT AAGACTTATCAAGAGACTA1 1 1 ILIAl 1 IAACAAI IAGAAAGI IAAGCAAIACAI 1 Al 1 1 1 IC TCTGGAATCCAGTGTTTCTTTTAAATACCTGTTAAGTTTGTATGCAACAI 1 ILIAAAGTTACC TACTTGTTAATTAAAAATTCAAGAG 1 11 11 111 IIIIAIIIIGAGG 1 1A1C1 1 1 1 1ACCACAGT TGCACAATATCCTTTTGAAGACCATAACCCACCACAGCTAGAACTTATCAAACCCTTTTGTGA AGATCTTGACtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctgga aggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctgggg ggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctat ggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCC GAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGG TAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACC GTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCAGAACAC AGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCG CCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGT CCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTG GAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGT CTTTGTTTCGTTIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGA GCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCC ATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGC GAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGC CCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTAC CCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGG AGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGA GGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAA CATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGAC AAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGC GTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGC CCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCG ATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCT GTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattt ttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCAATGGCTAAGTGAAGATGACAAT CATGTTGCAGCAATTCACTGTAAAGCTGGAAAGGGACGAACTGGTGTAATGATATGTGCAT ATTTATTACATCGGGGCAAAI 1 1 1 IAAAGGCACAAGAGGCCCIAGAI 1 ILIATGGGGAAGT AAGGACCAGAGACAAAAAGGTAAGTTAI 1 1 1 1 1 GA 1G 1 1 1 1 1 CCTTTCCTCTTCCTGGATCTG AGAATTTATTG G AAAACAG ATTTTGG GTTTCTTTTTTTCCTTCAGTTTTATTG AG GTGTAATT GACAAGTAAAAATTATATATAAATACAATGTATAATATGATGTTTTGATGTATGTGTATATA CATTGTGAAATGATTACTACAGTCAAACTACTTAACATATTCATCACCTCACATAATTATTAT TCTCCCCCCAGGGTGAAAGCATTTAAGATCTACAAGCTACAATTTTCAATTAT 2541 pARBI- 657: PTPN2_1Exogeno us_34 TAGTGACGGTATCAAGAGCAGCATCCCAGGTTGACTTTCTTTGGGGCAGGACCTTGCTTGT GTCTTAACCCTTGGTTCCTACccaagtttgtctctctagtcctcaactctgaaagccacttgatatcttacacaatt ccttttttgcctgagaaaataaaagtcagttttgatcatttacaaccaaaaatcctaactaacacaGACCTGTTTTTG AAATCAGGTAGATTGGAAGTCTTGGTTTACTTCTTATAAGCCCGTCCGCTGTCTGTCTTGTA ACATCCCAGGAGCAGACTTAACAAGGCCTTCCTGGAGCCTTGCTCTTTCTGTCTGCTTCCCTC ATCTGctctctctcctctctctTCACAGGGTCCACTTCCTAACACATGCTGCCA HILI GGCTTATGG TTTGGCAGCAGAAGACCAAAGCAGTTGTCATGCTGAACCGCtgacgactgtgccttctagttgccagc 2541 147 WO 2022/093846 PCT/US2021/056689 catctgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgagga aattgcatcgcattgtctgagtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgg gaagacaatagcaggcatgctggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTC AGTGGGCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAAT TGAACGGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTG GCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAAC GTTCI 1 1 1 1CGCAACGGGTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTC TCCTTCACGCGCCCGCCGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGC CGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGG TCGAGACCGGGCCTTTGTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCAC GCTTTGCCTGACCCTGCTTGCTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTAC AGATCCAAGCTGTGACCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAA GGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAA CGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGAC CCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCC TGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTC AAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCA ACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGC TGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACT ACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTT CAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAA CACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCC AAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACC GCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttac aaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatca atgtatcttatATTGTGGAGAAAGAATCGGTGAGTAATATTTAATATTTACAACTTAGTATACTG TATGTG ATCATTAG CATATAAAG ATTTTCATTTTG G G G CCAATATTCATTCCTTAGTTTTG G C CTTTAATTGCTAAAGGCTAGCGGTCAAAGTG 1 1 ILIGTCCGGAAAAACTCATGTATCCTTTTC CTTTCTTAAGTAI 1 1 1 1ATAACAATTGCAGACCTTTCATCTCCAAGATAGAAATACAATGGAA TAAATATGGACTAGCAGTGACATATAGATCTTTGGAATCCCTAGGAATCCTTATTGACCTAT TGTCAATAAGTCCTCTTCCAGCTTTAAGATCTTGTACTGTTCTACTTCAGATTTCTTACTTTAT TCTACATTTCATAATTGCTGG 1 1 1 1 1AATGATGATGAAAATTTCCTAATCCACTTCTAATTAGA TGTG GCAATGACATGCCpARBI- 658:PTPN22Exogeno us_35 CAGAATTTGAATATGATGTGGCTGACCATAGATACCTCCATTGCATTAATTCTGCTTCATAA AGTGTTTGATGCTTGCTTGTAGGTGTTGAATAGAGCCTAATTAGCAGTAAGTAAACAGATCT agagcacagactttggcatctgaaggaccttggttcaatgctgggactgccacttactagctatgggatctttggtggatt tttaacctttgaaagcctttcatccctcacagatataatggggaagaaaatcgtttccattagtattgtgaggattaaatg attaattgatgtaaacaatgtgctttccatagtacttggcatatcataagtgcttcatGTTATTTTACGCTGGCTGG GAAGATAAGTTTTGCTGTGGAGAATTTAAGAGGGATATTAAAATATA 1 1 1 1 IGTTATTTTAA GGAAATTCGAAATGAGTCCCATGACtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccc cgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagt aggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgct ggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCAC ATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGA GAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGA GGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGG GTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGC CGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGG TGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTT GTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTG CTTGCTCAACTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGA CCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGT TCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCA GCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCT GCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGT 2541 148 WO 2022/093846 PCT/US2021/056689 GCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGC CCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCG CGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGA CTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAA CGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCAC AACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGC GACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAG ACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCAC TCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatc acaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTATCCTC ATAGAGTGGCCAAGTTTCCAGAAAACAGAAATCGAAACAGATACAGAGATGTAAGCCCAT GTAAGTACTTGTGGGTTTGTGTGCATGTGTATTTTTTGGTTTGTTTTAGGAGGCAGGATGTA GTGAAAAGGAGGGCTTGGGGTCAGTGTTGATAAATACAGTAATTTTTTTCCTATTTACGTAA GACACGTTCTTTAAGAATTTAAAGGTGTAGAATAGTGGAAGGAAAAATAATTACCCATAAT TATTTCATCCTTCAAACATAGGCACCATTATTTTGGTGTATTTCCCACAACCTG 1 1 1 1 ICTTAT GCACAGTTTTCCTTTCTTTAAAATAATTGTAATTATAGATGTCTATATAATATCCATATGTATT TCCTTTTCATATCATTCCATCCCCTTTGTAAGTTTTGCTTAAAATAGTTATTGGTGTAGTTTGG llllllpARBI- 659:PTPN23Exogeno us_36 ACCAGTTATCGTTTTGTAGGTAGACCAATCAATTCTTAGGTACCAAGAATCTGAATGATCCT TTTACTTTTAGGAAGGTAAGTACTTTATTCATTTAACTATGTTTACTCCTGGTCGAI 1 1 1 ICAA GTCACAATGGCTAATGTGCTACAAACAGAAGTGCTTCCTTTCCAGCACTATAGTAATAAACA AGATTGCATTTTATACTCCTTACAAAAAAAGTAGAGAATAGTTTAGGATTTGTCTCAACTCTA TTATGATGCTAATTCAIIIIICIIAIIICIICIGICIIIIIATAAATACCTAGAATATTAATATG AAGATAAAAACAGTAATTTTGAAATGACAGTTGTGGTTTATCATTCTCTATTTTCAGATGATC ACAGTCGTGTTAAACTGCAAAATGCTGAGAATGATTATATTAATGCCAGTTTAGTTGACATA GAAGAGGCAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctgga aggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctgggg ggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctat ggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCC GAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGG TAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACC GTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGCCGCCAGAACAC AGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCG CCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGT CCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTG GAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGT CTTTGTTTCGTTIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGA GCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCC ATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGC GAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGC CCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTAC CCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGG AGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGA GGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAA CATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGAC AAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGC GTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGC CCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCG ATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCT GTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattt ttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCAAAGGAGTTACATCTTAACACAG GCAAGTAATACGATACCACGCAAATGTCTGAAAATGATGTGTTTGTGCTTGTTCTGCTTTAA ATCATAGGTAAAAGTATATCTTGACTTCTTTTGGAAATGAAATGGTATTTCAGI 1 1 1 1 1 ILIG ACGATGTAATGAATTATGGACATTATAAGGTTTTGAAGCTTTGAGTATTTAAGATAAAAGGC AAGTTAI 1 1 1 IGATATTACACGTTCTGTGAAGGAAAATTCTTAGGAAATGGCTTAGGCCAGT 2541 149 WO 2022/093846 PCT/US2021/056689 TCTTTGGCAGATTGTGTTCCTTACATTATATCTGACACAGAGTGCTGCTTATGCTTCTTAGTG TCI 1 LI 1 1 ILICTTCCCATACCCTGTGGCAAAACCAGAGGCCCTGGACAGCTCTTCTGTAGCT CCCCCTGCCTCGCATATATCTTCAGAGAGTACACCAAGCCCTGGATGGTGTpARBI- 660: PTPN6_1Exogeno us_37 CCTGCTCAAGGGCCGAGGTGTCCACGGTAGCTTCCTGGCTCGGCCCAGTCGCAAGAACCAG GGTGACTTCTCGCTCTCCGTCAGGTAGGTGGGCCCCCCGCAACCCCGGGCATTTTGGCCACT CTCTTGTG CC ATCCAG G CCCTG AACCACTCATTCCTG GTTCCCCGTG G CAGTG CTG ACTCCCC GTCTGTTCCCTTGCCCCCAACCCCCACACTCCCCATCCCTGTCTGTGCCCACCCATGCCCATG TGTGCCCCCACCCAGGACCTCAGCCGATCCCTGCCCTCCTGCCTCTACTCCTGCACCGACTG GCCTCACCGCCTGGTGCCCTGCAGGGTGGGGGATCAGGTGACCCATATTCGGATCCAGAAC TCAGGGGAI 1 ILIATGACCTGTATGGAGGGGAGAAGTTTGCGACTCTGACAGAGCTGGTG GAGTACTACACTCAGCAGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttcc ttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcatt ctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcg gtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCA CAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGG CGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGG GGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1 CGCAACGGGTTTGCCG CCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACC TGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCAGGGTGTCCTGCAG GACCGCGACGGCACCATCATCCACCTCAAGTACCCGCTGAACTGCTCCGATCCCACTAGTGA GAGGTGAGGGCTCCGCACCCCCGCCATTCCCAAGCAGGGATGAGCCGGCTCCCACCCTGAA CAGCCAGGGAGGCAGGGAGACTGGCAGCCGGCGCTGCCTACCCTCCATCCCCTCCCCTCCC TGCACCAGCTGGGGCTCTCAATGTCCCTCCTCCCTGCTGTCCTGGGACCTGGTGTCTCAGAG CCTAACCTACCACCCTTTCCACCTAACCCCGAGGAAGCCACAGAAAGCTGCCTCGCCCTACT CCGGGAGCCCTGGCCGCTGCAACCCAGGTCCCACTGGAGACAGGGAGGCCACTGCTGGTG GCCAGCATGTCGTGCAGGCCAGCTCTGTTGTTAGAAAGCTCTTCTTCCTCTGGAATCGAGCC TGCCT 2541 pARBI- 661:PTPN62Exogeno us_38 CTGGGTTCGAAGCCCGGTTAGAACTCTGGAGGCTAGGATGGCTTGAACCTGGGAGGTCGA GGCTGCAGAGAGCTGTAACCGCGCCACTGCACTCCAGCCTGGGCAACAGAGCTCTGGAAG CTTGCCCTAGAGTCAGTCAAGGGCCCTAGGCCAGTGAGTAACAGCTCAGCGTCAGTTTCCT CATCTATAAAATGGGGGTAATATCATACCTAGCTCTCAGCATGTTTGTGAGAGACCTAAATG AGGTGGTGGATTTGGAAGCATGTAGCGCAGTGCCTGGCACACAGTAGGTGCTTGATTTCCG GCCCCTCTCTGTGAATGTCTCTGCTCAGCGCCTTCCCCTGTGGCCTGGGTCTTACCTTCCCTG ACGCTGCCTTCTCTAGGTGGTACCATGGCCACATGTCTGGCGGGCAGGCAGAGACGCTGCT GCAGGCCAAGGGCGAGCCCTGGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgt gccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtag gtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgg ggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACAT 2541 150 WO 2022/093846 PCT/US2021/056689 CGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGA AGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAG GGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGGGT TTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCG CCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTG CCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGT CCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCT TGCTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACC GGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTC ACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGC GTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGC ACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGC AGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCC GAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCG CCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACT TCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACG TCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAA CATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGA CGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGAC CCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTC TCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcaca aatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatACGTTTCTT GTGCGTGAGAGCCTCAGCCAGCCTGGAGACTTCGTGCTTTCTGTGCTCAGTGACCAGCCCA AGGCTGGCCCAGGCTCCCCGCTCAGGGTCACCCACATCAAGGTCATGTGCGAGGTAAGGC AGCCAGGCGGCGGGGGAGCCTCTGCTGAGGCTCCTGTCTGTGACCACAGTGTGGGTGGCA GGGAGGGTCTGCCTGGGCTTGAATTCAAGGCTGGGGACCCAGGGAGGGAGACTCAAGTC CTGTGAATGGCCTAATTTGGCTCCCCCCAGGGTGGACGCTACACAGTGGGTGGTTTGGAGA CCTTCGACAGCCTCACGGACCTGGTGGAGCATTTCAAGAAGACGGGGATTGAGGAGGCCT CAGGCGCCTTTGTCTACCTGCGGCAGGTCAGGGGTGGGCCCAGCTGCCTCCCCACTTCCCCT GAGCTGTCCCCCAGATGTpARBI- 662:PTPN63Exogeno us_39 TGTCACATATGTGCAATGCCATGCTCCTGAGCCTTTGATTGCAGACGTGTGGGAAGTGGGC CCCGTCCCCACCCCCAGTGCCACCCTGCTCTGCTTCTCTTCCCTTGCTGTGCTCTAAAACGAG AAGTACAAGTGAGTTCCCCCAAGGGGTCGGCCGCGCCTCTTCCTGTCCCCGCCCTGCCGGC TGCCCCAGGCCAGTGGAGTGGCAGCCCCAGAACTGGGACCACCGGGGGTGGTGAGGCGG CCCGGCACTGGGAGCTGCATCTGAGGCTTAGTCCCTGAGCTCTCTGCCTGCCCAGACTAGCT GCACCTCCTCATTCCCTGCGCCCCCTTCCTCTCCGGAAGCCCCCAGGATGGTGAGGTAAGGG CCTGCCACCCACGGTAGACAGGAGGCAAGGGTGCCTGGTGCCCACGGGACCCCTCCTCACT GCCCTGCCTGGGCCGCCCAGGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgc cttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtg tcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgggga tgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGG TGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTG GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGC CGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCT ACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTC CTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCG GCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGC TCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGC GCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG 2541 151 WO 2022/093846 PCT/US2021/056689 AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA AG G AG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTGGTTTCACCGA GACCTCAGTGGGCTGGATGCAGAGACCCTGCTCAAGGGCCGAGGTGTCCACGGTAGCTTC CTGGCTCGGCCCAGTCGCAAGAACCAGGGTGACTTCTCGCTCTCCGTCAGGTAGGTGGGCC CCCCGCAACCCCGGGCATTTTGGCCACTCTCTTGTGCCATCCAGGCCCTGAACCACTCATTCC TGGTTCCCCGTGGCAGTGCTGACTCCCCGTCTGTTCCCTTGCCCCCAACCCCCACACTCCCCA TCCCTGTCTGTGCCCACCCATGCCCATGTGTGCCCCCACCCAGGACCTCAGCCGATCCCTGC CCTCCTG CCTCTACTCCTG CACCG ACTG G CCTCACCG CCTG GTG CCCTG CAG G GTG G G G G AT CAGGTGACCCATATTCGGATCCAGAACTCAGGGGA1 1 1 LI ATGACCTGTATGGAGGGGAGA AGTTTGpARBI- 663:PTPRC_1_ Exogenou s_40 TCTTTAGCTAATGTTCTGTAGCTTGTTTTAGATCTGTGTCTACATATTATATGTATCTCTGTAT GCATCAATATTTGTATATATGCATGCATATATGTGTATGTATATTTATGAATACATATACACA CCATATACATACACTTATGTATGGTGTGTGCATATGTATGTGTAGATATATGTACATACACA CTATAGTGGACTGGGGAGTTAGTATACTGGGAGGAGCATACATTTAGGGTATGATTCACAT ATTTATTTTGTCCTTCTCCCATTTTCCATTAATTAACAGGATTGACTACAGCAAAGATGCCCA GTGTTCCACTTTCAAGTGACCCCTTACCTACTCACACCACTGCATTCTCACCCGCAAGCACCT TTGAAAGAGAAAATGACTTCTCAGAGACCACAACTTCTCTTAGTCCAGACAATACTTCCACC CAAGTATCCCCGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctg gaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctgg ggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctct atggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCC CGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGG GTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAA CCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1 CGCAACGGGTTTGCCGCCAGAAC ACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGC CGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGC GTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTT GGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTAC GTCTTTGTTTCGTIIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTA GAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGC CCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGG GCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCT GCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCT ACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCA GGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTC GAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGC AACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCG ACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCA GCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCT GCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCG CGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAG CTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagca tttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGACTCTTTGGATAATGCTAGTGC TTTTAATACCACAGGTTGGCACACAAAAGTTGTTAACTTAAATATCAGGGAATGTCATTTAG AAAATTCTACAGTTATCAGTACAACTTGTCTTTAAATTATTTGCACAGI 1 1 L1AAGTATGTGA TTTTATTCAAGTGCAGAAATTGCAGGAAATTAGTATCTGTGAAATATAGATCGACTGAAGTA ATTAATGCATGTTGTTAGGGAGTGGAGAGAGAAAAGAAGGGAAGCAAGATCTCCAAGGAC AATCAGGAGGGGAAATTTGTTCTAGTATCCTCTGATCTATACACACTCGCCATGATTCTCCC 2541 152 WO 2022/093846 PCT/US2021/056689 GCTTGGCTTCCCGCCACCTGGACAGATGAGAATTTCCCTAGTTCAGAGATTATCAGTTCTAC TCTCCTTGGAAGGTGTCTTAAATGGGAGTCTTCCCATTTCTTTGTTTCACTCTAGApARBI- 664:PTPRC_2_ Exogenou s_41 AGGGAAI 1 1 1 1AIATGTTGGTCATATTATATCCCTAGCATGTGGCATAATGTCTAGCACAAA ATAG GTG CTCAATTAATCATC ATTATCTA AATAAATAATG CATTTG G G AAAAAAAAGTTTCA AAAGI 1 1 1 1CAAAAGTCTTTTGCAGGCTTGAAATTAATCCCAATAGTGATCCTTTAGTCTGTT ATGI 1 ILIGATTTAGCCTGGGGATTCAAAAAATAAATAACATAATTTTGATATATTTGGGCTT TGTAAACATGGTACTAAGAGAGGAAATATAGTTTCATTAGGGTAAAAGCTACTGAAAATTG CCACTTGGTGAATGTTCTATCATAGACTTGAGGTACATATAAAAATCTAATATATGTTTACAT TAATATGAATGAAATTTGAAATTTTCTAAGAGAI 1 1 1 1 GTTTCTTCTTTGCAGGGCAAAGCCC AACACCTTCCCCCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccct ggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctg gggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggct ctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTC CCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGG GGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGA ACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCAGAA CACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGG CCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTG CGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCC TTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTA CGTCTTTGTTTCGTTTICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCT AGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGT GCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGA GGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAA GCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCC GCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGT CCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAA GTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATG GCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGAC GGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGC TGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAA GCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGAC GAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatACTGGTAAGAATTAATATTT ATAI 1 1 1 1ACTAATTTTATTTTCTTGTTGCAAAGTTTATATATTTAACTACAATTTTCTATTATT AACACTGAAATTAI 1 1 1 1AAGGATAAATTTTATAATCATGAGTGATTCTTGACATTCACTTGT TCTTAAACI 1 ILIGCTTATACGTTATAGAGTTTAATAACTACCTAAACATGTTATTAAATTTGT ATATATATTTTGTGTATAAATAGTAACTTTTCCCAAACTTGACAGTAAATCACACAACAGGTT TCTACTCTCTTTTAATATTTTAAGACTATAAAAAAATGCATTTAAATTAGATAACAAAATTTTA TAGTCTGAAAGCAGGTTAACAGCTGTCTATGTATGTTATAGATATGTAGATAACAGATTTGC ATATGTCTATATTTCTTTAAGAGTATGTTGCI Illi 1CAATGGTATGCA 2541 pARBI- 665:PTPRC_3_ Exogenou s_42 CCTTTAGCACCATAAAGAAACTAAATTA 1 1 IAGATGI 1 1 1 1A1 GAGAACATATCAAAAAGTA CHI 1CTGTCATCCAATACTTCCACAAATAAATCATTAGTTCTTGCTAATCTTCATCTGGCATA AAAATAATGACATCAACTTTCTTCATGTAATTTCCCACTTAATTCCTTTACTAGGAGCAATAT CAATTCCTATATGACGTCATTGCCAGCACCTACCCTGCTCAGAATGGACAAGTAAAGAAAAA CAACCATCAAGAAGATAAAATTGAATTTGATAATGAAGTGGACAAAGTAAAGCAGGATGCT AATTGTGTTAATCCACTTGGTGCCCCAGAAAAGCTCCCTGAAGCAAAGGAACAGGCTGAAG GTTCTGAACCCACGAGTGGCACTGAGGGGCCAGAACATTCTGTCAATGGTCCTGCAAGTCC AGCTTTAAATCAAGGTtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttg accctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattct attctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggt gggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCAC AGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGC GCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGG 2541 153 WO 2022/093846 PCT/US2021/056689 GAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGC CAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCT GAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTCATAGGAAAAGACA TAAATGAGGAAACTCCAAACCTCCTGTTAGCTGTTAI 1 1L1A1 1 1 1 1GTAGAAGTAGGAAGT GAAAATAGGTATACAGTGGATTAATTAAATGCAGCGAACCAATATTTGTAGAAGGGTTATA TTTTACTACTGTGGAAAAATATTTAAGATAGTTTTGCCAGAACAGTTTGTACAGACGTATGC TTATTTTAAAATTTTATCTCTTATTCAGTAAAAAACAACTTCTTTGTAATCGTTATGTGTGTAT ATGTATGTGTGTATGGGTGTGTGTTTGTGTGAGAGACAGAGAAAGAGAGAGAATTCTTTCA AGTGAATCTAAAAGCTTTTGCTTTTCCTTTG 1 1 1 1 1ATGAAGAAAAAATACATTTTATATTAG AAGTGTTAACTTAGCTTGAAGGATCTG 1 1 1 1 1AAAAATCATAAACTGTGTGCAGACTCAATApARBI- 666:PTPRCAP1_Exogenous_43 aaggaaaaaggcactgagtgctggggggtgctggggtgggctgcagtgatagacatcagggtagaggttaaggtcag gttcagcctcactggggtgaagtttgagcacggtgagcaggccatgcagcccgggggaggggaggatgggaggaggt ggagctttccgggcagagggaacagccagtgcgaaggccccaggcaggtggcttaatgcagctgttgggggaggtgag tggtagggaggaggctggagggatgggggctgatctcacagggccagagcctggttgaccaaataaggccttggccttt tctGCTTGGCTGTCCCAAGAGGATCCCAAAGAGAAAAAAACGAAAGTGGTCTTGGTCACCCA GCCTGCCCCACACCAGGCCCCACCCCAGGTGCTGAGCCCTCTGAGCCCCTGCCTGTCTCCCA CAGGCTCTGCCCTGCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgac cctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctatt ctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgg gctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAG TCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGC GGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGA GAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCA GAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTG AGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAA CTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCT CCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACT CTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTAC TCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTG GTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGC GAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGC AAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCA GCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTA CGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTG AAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAG G ACG G CAACATCCTG G G G CAC AAG CTG G AGTACAACTACAAC AG CCAC AACGTCTATATCA TGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGG ACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGT 2541 154 WO 2022/093846 PCT/US2021/056689 GCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAG AAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGG ACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaat aaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatACCTTAGGGCTCGGGAT GCTGCTGGCCCTGCCAGGGGCCTTGGGCTCGGGTGGCAGCGCGGAGGACAGCGTGGGCT CCAGCTCTGTCACCGTTGTCctgctgctgctgctgctcctactgctgGCCACTGGCCTAGCACTGGCCT GGCGCCGCCTCAGCCGTGACTCAGGGGGCTACTACCACCCGGCCCGCCTAGGTGCCGCGCT GTGGGGCCGCACGCGGCGCCTGCTCTGGGCCAGCCCCCCAGGTCGCTGGCTGCAGGCCCG AGCTGAGCTGGGGTCCACAGACAATGACCTTGAGCGACAGGAGGATGAGCAGGACACAG ACTATGACCACGTCGCGGATGGTGGCCTGCAGGCTGACCCTGGGGAAGGCGAGCAGCAAT GTGGAGAGGCGTCCAGCCCAGAGCAGGTCCCCGTGCGGGCTGAGGAAGCCAGAGACAGT GACACGpARBI- 667: PTPRCAP_2_Exoge nous_44 aaggtcaggttcagcctcactggggtgaagtttgagcacggtgagcaggccatgcagcccgggggaggggaggatggg aggaggtggagctttccgggcagagggaacagccagtgcgaaggccccaggcaggtggcttaatgcagctgttggggg aggtgagtggtagggaggaggctggagggatgggggctgatctcacagggccagagcctggttgaccaaataaggcct tggccttttctGCTTGGCTGTCCCAAGAGGATCCCAAAGAGAAAAAAACGAAAGTGGTCTTGGT CACCCAGCCTGCCCCACACCAGGCCCCACCCCAGGTGCTGAGCCCTCTGAGCCCCTGCCTGT CTCCCACAG G CTCTG CCCTG CACCTTAG G G CTCG G G ATG CTG CTG G CCCTG CCAG G G G CCT TGGGCTCGGGTGGCAGCGCGGAGGACAGCtgacgactgtgccttctagttgccagccatctgttgtttgcc cctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattg tctgagtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcag gcatgctggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAG CGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCC TAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 IC CCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAA CGGGTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCC CGCCGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTG TGGTGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGC CTTTGTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGAC CCTGCTTGCTCAACTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCT GTGACCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAG CTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAG TTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTC ATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGG CGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCA TGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGAC CCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCAT CGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCA CAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGC CACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCG GCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAA AGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGAT CACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatag catcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGTG GGCTCCAGCTCTGTCACCGTTGTCctgctgctgctgctgctcctactgctgGCCACTGGCCTAGCACTG GCCTGGCGCCGCCTCAGCCGTGACTCAGGGGGCTACTACCACCCGGCCCGCCTAGGTGCCG CGCTGTGGGGCCGCACGCGGCGCCTGCTCTGGGCCAGCCCCCCAGGTCGCTGGCTGCAGG CCCGAGCTGAGCTGGGGTCCACAGACAATGACCTTGAGCGACAGGAGGATGAGCAGGACA CAGACTATGACCACGTCGCGGATGGTGGCCTGCAGGCTGACCCTGGGGAAGGCGAGCAGC AATGTGGAGAGGCGTCCAGCCCAGAGCAGGTCCCCGTGCGGGCTGAGGAAGCCAGAGAC AGTGACACGGAGGGCGACCTGGTCCTCGGCTCCCCAGGACCAGCGAGCGCAGGGGGCAG TGCTGAGGCCCTGCTGAGT 2541 pARBI- 668:PTPRCAP cagtgcgaaggccccaggcaggtggcttaatgcagctgttgggggaggtgagtggtagggaggaggctggagggatg ggggctgatctcacagggccagagcctggttgaccaaataaggccttggccttttctGCTTGGCTGTCCCAAGAG GATCCCAAAGAGAAAAAAACGAAAGTGGTCTTGGTCACCCAGCCTGCCCCACACCAGGCCC 2541 155 WO 2022/093846 PCT/US2021/056689 _3_Exoge nous_45CACCCCAGGTGCTGAGCCCTCTGAGCCCCTGCCTGTCTCCCACAGGCTCTGCCCTGCACCTT AGGGCTCGGGATGCTGCTGGCCCTGCCAGGGGCCTTGGGCTCGGGTGGCAGCGCGGAGG ACAGCGTGGGCTCCAGCTCTGTCACCGTTGTCctgctgctgctgctgctcctactgctgGCCACTGGCC TAGCACTGGCCTGGCGCCGCCTCAGCCGTGACTCAGGGGGCTACTACtgacgactgtgccttctag ttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaa atgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggggtggggtggggcaggacagcaaggggga ggattgggaagacaatagcaggcatgctggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGC CCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCG GCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTG TACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCG TGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCG CATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCG TTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAG CTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGC TCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCG CCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGG TGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCG ACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCA AGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTG ACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACG ACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGAC GACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGC ATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAG TACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGG TGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCA GCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACC CAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTC GTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttata atggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaa actcatcaatgtatcttatCACCCGGCCCGCCTAGGTGCCGCGCTGTGGGGCCGCACGCGGCGCCT GCTCTGGGCCAGCCCCCCAGGTCGCTGGCTGCAGGCCCGAGCTGAGCTGGGGTCCACAGA CAATGACCTTGAGCGACAGGAGGATGAGCAGGACACAGACTATGACCACGTCGCGGATGG TGGCCTGCAGGCTGACCCTGGGGAAGGCGAGCAGCAATGTGGAGAGGCGTCCAGCCCAG AGCAGGTCCCCGTGCGGGCTGAGGAAGCCAGAGACAGTGACACGGAGGGCGACCTGGTC CTCGGCTCCCCAGGACCAGCGAGCGCAGGGGGCAGTGCTGAGGCCCTGCTGAGTGACCTG CACGCCTTTGCTGGCAGCGCAGCCTGGGATGACAGCGCCAGGGCAGCTGGGGGCCAGGG CCTCCATGTCACCGCACTGTAGAGGCCGGTCTTGGTGTCCCATCCCpARBI- 669:RPS23_1_ Exogenou s_46 ATAGAGTAGGGCGGGGGATGCCATGGAGAGGCTCCATGGGGGAGGGCCGGGGAAGCGC CGCTCCAGGAGGCACGTGGTCCGGCGCGGAAGGGGCCCATGAGGCGTGGAGGCCGCCGA GGTCGGGGTACCGAGGGACGCAGGGAGGCCAGCGCTTCCTCCCGGGCATTCGAGCGGGG CCTCGTCCTTCGGGAGAACACATTCTCCGGAGCCCTCTTCGAACGTTTATTAGTCGGTTCAG GG CAACTTG AAG G CCAAATGTTTG G CCCAC AG G CCAATAAATAGTACG AG AG CCA ATCG G CTTAAGGGTTTATTCCAGGTGAGGCGAGTGTCTTAGAAGATGGGAAACACGTAGATGGCG TGI 1 1 1 IACGGAAGAACIAAAAIAI1 IAAI 1 1 1 1AGGCAAGTGTCGTGGACTTCGTACTGCT AGGAAGCTCCGTAGTCACCGACGAGACCAGtgacgactgtgccttctagttgccagccatctgttgtttgcc cctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattg tctgagtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcag gcatgctggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAG CGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCC TAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 IC CCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAA CGGGTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCC CGCCGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTG TGGTGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGC CTTTGTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGAC 2541 156 WO 2022/093846 PCT/US2021/056689 CCTGCTTGCTCAACTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCT GTGACCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAG CTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAG TTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTC ATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGG CGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCA TGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGAC CCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCAT CGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCA CAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGC CACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCG GCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAA AGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGAT CACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatag catcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatAAG TG G CATG ATAAACAGTATAAG AAAG CTCATTTG G G CACAG CCCTAA AG G CCAACCCTTTTG GAGGTGCTTCTCATGCAAAAGGAATCGTGCTGGAAAAAGTGTAAGTCCATTGCTCCCGTCA AGTTTTAGTTTATTATAGGAATTCGAGACATGAACTTACGAATTCTTGTTTTGAAAGTAATTG CAGGI 1 1 1 1GTGTAGTAGTATTCATTTGGGCATTGTGGGGTAAAATTGCAAAGCGTTTGTTC TATTTAAAAGTTGGTAAAATTAG 1 1 1 1 1GGGAATTAGGTAGTTAAGGTTTTAATTTAACGTT GGCCTGGAAGGAATTGGAGAAGATACTAGCAATGATGAAGTAAAGGACACAAACACCTTT ACTGTGGGAGTTGTTATAAGTAAATGGCACGTGTCAGCTATTGAACTTTATCGACTTGATAA AACTAAGGTGAAGAGApARBI- 670:RPS23_2_ Exogenou s_47_48 CAAGCGGGACTTGGGGTCTTGGGGACGGGCGGGCGGATGCGAATAGAGTAGGGCGGGG GATGCCATGGAGAGGCTCCATGGGGGAGGGCCGGGGAAGCGCCGCTCCAGGAGGCACGT GGTCCGGCGCGGAAGGGGCCCATGAGGCGTGGAGGCCGCCGAGGTCGGGGTACCGAGG GACGCAGGGAGGCCAGCGCTTCCTCCCGGGCATTCGAGCGGGGCCTCGTCCTTCGGGAGA ACACATTCTCCGGAGCCCTCTTCGAACGTTTATTAGTCGGTTCAGGGCAACTTGAAGGCCAA ATGTTTGGCCCACAGGCCAATAAATAGTACGAGAGCCAATCGGCTTAAGGGTTTATTCCAG GTGAGGCGAGTGTCTTAGAAGATGGGAAACACGTAGATGGCGTGI 1 1 1 IACGGAAGAACT AAAATATTTAATTTTTAGGCAAGTGCCGCGGAtgacgactgtgccttctagttgccagccatctgttgtttg cccctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcat tgtctgagtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagc aggcatgctggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGA GCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTG CCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCTTT TTCCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICG CAACGGGTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGC GCCCGCCGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGC CTGTGGTGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCG GGCCTTTGTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCT GACCCTGCTTGCTCAACTCTACGTCTTTGTTTCGTTITCTGTTCTGCGCCGTTACAGATCCAA GCTGTGACCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAG GAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCAC AAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAG TTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTA CGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCC GCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACA AGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGG GCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACA GCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGAT CCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCC ATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGA GCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCG GGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagc 2541 157 WO 2022/093846 PCT/US2021/056689 dalagcalcacddalllLdcdddlddagcalllLLLLLdcLgcalLlagllgtgglllgLlddaclcaldatglallld tCTTCGTACTGCTAGGAAGCTCCGTAGTCACCGACGAGACCAGAAGTGGCATGATAAACAG TATAAGAAAGCTCATTTGGGCACAGCCCTAAAGGCCAACCCTTTTGGAGGTGCTTCTCATGC AAAAGGAATCGTGCTGGAAAAAGTGTAAGTCCATTGCTCCCGTCAAGTTTTAGTTTATTATA GGAATTCGAGACATGAACTTACGAATTCTTGTTTTGAAAGTAATTGCAGG Hill GTGTAGT AGTATTC ATTTG G G CATTGTG G G GTAAA ATTG CAAAG CGTTTGTTCTATTTAAAAGTTG GTA AAATTAGI 1 1 1 1GGGAATTAGGTAGTTAAGGTTTTAATTTAACGTTGGCCTGGAAGGAATTG GAGAAGATACTAGCAATGATGAAGTAAAGGACACAAACACCTTTACTGTGGGAGTTGTTAT AAGTAAATGGCACGTGTCApARBI- 671:RTRAF_1_ Exogenou s_49 TTGTATATCCI 1 1 1 IAAAGTTATTCI 1 1 1 IAGI FAATTGCTCTATGTGTATTGAGACTAGGAAT CAGAAAGCTTAGATTCTAGTCCCAGGTGTAAGTTGTGTAACCCTTGGCAAGTGTCAATCTCT AGGCCTCAGCI 1 1 LI CAIC1 Al AAAAIGAGGAAG 1 IG ICG IAI ICIAI 1 1 1 1 1 1 ICTTAAGAT GATACACTTAAATGTTCCCTTCTGTTGGGTTATATAATTGCATCAAAAGTGTAGTAATGTTAT TAAAAAATTGTTAGAGATCCAAACTAAGGTCTCTTTCAACTCTCCCATTCI Illi ICIGTGACT TTATGGTAATAATGAAACTGGTGGTTTTCTTTTCTTCCCCCTCACAGTATCTCAGAGATGTTA ACTGTCCTTTCAAGATTCAAGATCGACAAGAAGCTATTGACTGGCTTCTTGGTTTAGCTGTT AGACTTGAAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaa ggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggg gtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctatg gGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCG AGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGGT AAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACC GTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCAGAACAC AGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCG CCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGT CCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTG GAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGT CTTTGTTTCGTTIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGA GCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCC ATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGC GAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGC CCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTAC CCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGG AGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGA GGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAA CATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGAC AAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGC GTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGC CCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCG ATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCT GTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattt ttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTATGGAGATAATGGTACGTTTTGTG GGGAATGTGTATTTTAAAGAGAGAGGAAAGATGGGAAAGGGAGTGTGAAAATGTAGGGA ACTTTGCAGTTTGTTTTGTCTAGTACTATTTTACCTTTGGTTTATTCTTATCACAAGTTAAAAG CACTTTTATTGTCTTTCATTGGTGTTTATATAI 1 ICIGTTAGAATTTGGAAATGGTGCCCTCTG GAGAAGGCTAATTGACTGTCTTCTCACAGAGTAACACTACTTTGATAATATGGTCTGCACCT TAGCCTTTCAAATTAAATTG 1 1 1 1 1AGTGTCCCAGAATTGATGGGACTTTGAAGTGTTGTTGC AGTAGGTAAI 1 ICICAAAAGACTGAAACATGTCTAATGCCAATATACATTAATACTCTATAG GCCAGAATATATTACTTATGTTTACTGTCTTAGCACAGATACTTCTATGGT 2541 pARBI- 672:RTRAF_2_ Exogenou s_50 GCACCTGTTATGTAGGAGGAGTAATAAAATGAATGAATGCACTCAAAACACTAAACAGTAA TTCTGTAATCCAACGGGAGGTACAGCGAATACCAAAAGCCTACATATACTATTCTCTGCATG CTATAG CA AG AAAG AAAG G A AAGTG G CTTCCCG GTG GTTTTCTG CCTATTGTAC AACCAG G AAGCTGACAATAAAGTTTATTTGAGCGTCGACGTGCGCCGACGTGGCCCCGCCTCCCCAGC CGGAGCCGCGATTGGTGGGCATTTGCCGGCGGCCACCGCTTTTAAGCCACGATTGGCGAA GGCCGCCGTCATTTCGGAGCGACTCAGCGCCTGCCCGCCCTCTCGCCGCGTCGCCGGTGCC 2541 158 WO 2022/093846 PCT/US2021/056689 TGCGCCTCCCGCTCCACCTCGCTTCTTCTCTCCCGGCCGAGGCCCGGGGGACCAGAGCGAG AAGCGGGGACCATGTTCCGACGCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgt gccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtag gtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgg ggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACAT CGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGA AGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAG GGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGGGT TTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCG CCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTG CCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGT CCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCT TGCTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACC GGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTC ACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGC GTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGC ACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGC AGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCC GAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCG CCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACT TCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACG TCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAA CATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGA CGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGAC CCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTC TCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcaca aatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatAAGTTGACG GCTCTCGACTACCACAACCCCGCCGGCTTCAACTGCAAAGGTGAGGCGGCGGCCTCAGCCC GGCCGCGTGTCCCTGACCTGGGCGGAGGTCCCAGCCTCAGTGCCCGCACCCCACCTCCCCG TCGGGACCCTCGGCGGCCTGGTTTCCGCCGGCAGCCTCCGGGCCCCTCTCCTCTGGGTCGC CACGTACCTCGGCTCTTCGCCGCCCCTTCCCGCCTTTAAAGCCCTCTCACCTACTCCTGTCTC GGCATGTTACI 1 ILIGCACTTGCTTAACTCCAAGCATCACGTAACTACCTTCTCTGTACATAA AAGGGAGAGCATTCGTCI 1 ILICACTCACTATTCAACTCCATGGTTCCCTGGGTAATTAGGC GATACCTTGAGCACCTGCTAATTATGGGCCAGCGCGGTGCTGGATTCTGAGGAAGGTGCTG AGTAACTTGpARBI- 673:RTRAF_3_ Exogenou s_51 CACTAAACAGTAATTCTGTAATCCAACGGGAGGTACAGCGAATACCAAAAGCCTACATATA CTATTCTCTGCATGCTATAGCAAGAAAGAAAGGAAAGTGGCTTCCCGGTGGTITICTGCCTA TTGTACAACCAGGAAGCTGACAATAAAGTTTATTTGAGCGTCGACGTGCGCCGACGTGGCC CCGCCTCCCCAGCCGGAGCCGCGATTGGTGGGCATTTGCCGGCGGCCACCGCTTTTAAGCC ACGATTGGCGAAGGCCGCCGTCATTTCGGAGCGACTCAGCGCCTGCCCGCCCTCTCGCCGC GTCGCCGGTGCCTGCGCCTCCCGCTCCACCTCGCTTCTTCTCTCCCGGCCGAGGCCCGGGGG ACCAGAGCGAGAAGCGGGGACCATGTTCCGACGCAAGTTGACGGCTCTCGACTACCACAA CCCCGCCGGCTTCAACTGCAAAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgc cttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtg tcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgggga tgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGG TGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTG GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGC CGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCT ACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTC CTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCG GCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGC TCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGC GCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC 2541 159 WO 2022/093846 PCT/US2021/056689 GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA AG G AG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGGTGAGGCGGC GGCCTCAGCCCGGCCGCGTGTCCCTGACCTGGGCGGAGGTCCCAGCCTCAGTGCCCGCACC CCACCTCCCCGTCGGGACCCTCGGCGGCCTGGTTTCCGCCGGCAGCCTCCGGGCCCCTCTCC TCTGGGTCGCCACGTACCTCGGCTCTTCGCCGCCCCTTCCCGCCTTTAAAGCCCTCTCACCTA CTCCTGTCTCGGCATGTTACI 1 ILIGCACTTGCTTAACTCCAAGCATCACGTAACTACCTTCTC TGTACATAAAAGGGAGAGCATTCGTCTTTCTCACTCACTATTCAACTCCATGGTTCCCTGGG TAATTAGGCGATACCTTGAGCACCTGCTAATTATGGGCCAGCGCGGTGCTGGATTCTGAGG AAGGTGCTGAGTAACTTGAAGACTAGTTCACTGCCTGCCAGGAGCTAAAGGGACGAGGGG TGGAAGpARBI- 674: SERF2_1_ Exogenou s_52 CCGGGTTAGGCATAGGCCCTCCCGGATCTTCCGCGGTGTAAGGAGAAGGCCAGCGCCCCT GTGATAGGCCCAGAGCCCCCACTCCACAAGCCAGCCCATCCCCCACGGAGACCCAAACCGT CCACACACACCTTGCCAGCTGTTTGGGCCCCACGCCGCCCCAAAACACGCCTCCAGCTGGCC CCTTGGGACCTCCCTTCTCTAGTCCGTATTTTGACCTGGCCCGTGGCAGATTCGCCACTCCCC CCTACCCCAAGCAGCCTGGGCCTCGATGGGCCGTTGTCGGGGCCCGGAGATTGAAGTGGT GTTGGATCCTGCTGCTGGCCGCGCTGGGGTAGAAGGGTCGCCGGTGTGTGGGCAGAGCG GCCCCCGCGTCTCACCTTTAATTTTCTTTCCTTAGGCGGTAACCAGCGTGAGCTCGCCCGCCA GAAGAATATGAAAAAGCAGAGCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgt gccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtag gtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgg ggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACAT CGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGA AGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAG GGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGGGT TTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCG CCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTG CCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGT CCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCT TGCTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACC GGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTC ACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGC GTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGC ACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGC AGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCC GAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCG CCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACT TCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACG TCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAA CATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGA CGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGAC CCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTC TCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcaca aatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGACTCGGTT AAGGGAAAGCGCCGAGATGACGGGCI 1 ILIGCTGCCGCCCGCAAGCAGAGGTAGCCCCAG 2541 160 WO 2022/093846 PCT/US2021/056689 GGAGGGGAGGGAAAGGGACGGTGGAGACCTGGGTTAGACCAAGGGTTATAGAAGGAAA GAGAGCTACCTCAGGGCTTGAATGTGGACTAGTCGTGAGGAGCAGAGTGCATTGCTTCCTC TAGGGTTTTATTTCCTCCCCACCCTCCAAATTGTTAGCTCACAGCCTTACAGGAAAGGACGG GGGCGGGCGCCTGCCCTCAGTCTGATTTCTGAGCGTCCCTGGGTCTGACCTTAAGGGCAAG GGCAGGGAGCTTCACATTTCAAATACAGTTGTGGTTACGGCAGCCCAGTACTTTTGGCCCTC CTTGCTGTTCGGTTCTCCTCCCTTCTCCCAACCTCCTCACTGGTGTTGCTGGGTGTGGTCCTC AATACAGAATAGAGpARBI- 675: SERF2_2_ Exogenou s_53_54 AATCGAGCCCTTTGCCCACGGCTACTTCACGGGACCACCCTCCCGGGTTAGGCATAGGCCCT CCCGGATCTTCCGCGGTGTAAGGAGAAGGCCAGCGCCCCTGTGATAGGCCCAGAGCCCCC ACTCCACAAGCCAGCCCATCCCCCACGGAGACCCAAACCGTCCACACACACCTTGCCAGCTG TTTGGGCCCCACGCCGCCCCAAAACACGCCTCCAGCTGGCCCCTTGGGACCTCCCTTCTCTA GTCCGTATTTTGACCTGGCCCGTGGCAGATTCGCCACTCCCCCCTACCCCAAGCAGCCTGGG CCTCGATGGGCCGTTGTCGGGGCCCGGAGATTGAAGTGGTGTTGGATCCTGCTGCTGGCC GCGCTGGGGTAGAAGGGTCGCCGGTGTGTGGGCAGAGCGGCCCCCGCGTCTCACCTTTAA TTTTCTTTCCTTAGGCGGTAACtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgcc ttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgt cattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggat gcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGG TGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTG GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGC CGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCT ACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTC CTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCG GCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGC TCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGC GCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA AG G AG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCAGCGCGAGCT TGCCCGCCAGAAGAATATGAAAAAGCAGAGCGACTCGGTTAAGGGAAAGCGCCGAGATG ACGGGCTTTCTGCTGCCGCCCGCAAGCAGAGGTAGCCCCAGGGAGGGGAGGGAAAGGGA CGGTGGAGACCTGGGTTAGACCAAGGGTTATAGAAGGAAAGAGAGCTACCTCAGGGCTTG AATGTGGACTAGTCGTGAGGAGCAGAGTGCATTGCTTCCTCTAGGGTTTTATTTCCTCCCCA CCCTCCAAATTGTTAGCTCACAGCCTTACAGGAAAGGACGGGGGCGGGCGCCTGCCCTCAG TCTGAI 1 ILIGAGCGTCCCTGGGTCTGACCTTAAGGGCAAGGGCAGGGAGCTTCACATTTC AAATACAGTTGTGGTTACGGCAGCCCAGTACTTTTGGCCCTCCTTGCTGTTCGGTTCTCCTCC CTTCTCCCAACCTC 2541 pARBI- 676: SLC38A1_ l_Exogen ous_55 TTCAAAAGGAATC1 HUGH 1 CAACTATTAGGATC1 1 1 1 1AAATCAAATATGTA1 1 1 IAATG GTGTACACCAGACCTGAAGAAAAAGATCACAGAAGGAATTTCCCCTTTGTAAGATAGAGGT AGTTAAAAATAAGCCTTATGACCTAATAGGTTAATTGTAATGCTCTGGTAGCCAACTTGAAA AAGGAGAAATGATGGTTGCATCTCACATTTTAAAATGTTAAGAATTTGTTTTGTAATGAGGA TACCTTAACCCCTGAAGGCCAAAATGACTATTTGTGTGAGTTTGAGAAAGGCACATAGTAA CTTGGGGAACAGTCAATAGAATGACAAAATCTTGACTATTTTAACI 1 1 L1GAACCCTGTCAT TTCTTGTGTTCTCAAATTTGAI 1 1 1 1AAATAGGCTGCATGGTGTATGAAAAGCTGGGGGAAC 2541 161 WO 2022/093846 PCT/US2021/056689 2541 AAGTCTTTGGCACCACAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttcctt gaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattc tattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcgg tgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCAC AGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGC GCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGG GAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGC CAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCT GAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGGGAAGTTCGTAATC TTTGGAGCCACCTCTCTACAGAACACTGGAGGTAAAAAGAACATGCTTTTCTTTACATAACT TGAAACTAATTCTGGTGGATGAGCGGCCACATGAATTTTAACATAATTCAAGCAGTTATCAT CCTCATTGCTAAAATGGCACAGGGAAAGTAAAGCAGAGACAGCAGTCACTTATTTAAAGCC ACAAATCCTGCTAGAGTAGCTGAAGTTGCCTTTGTGTCTTACTGACAGTTGGTCTAAGAACG GGCTGATAACI 1 1 1 1ATGTAGCTTGCAACATAAGCCTTCGTATCTTCTTTCTAAAAATGTTCT CATTTTCCTTCAGCAATGCTGAGCTACCTCTTCATCGTAAAAAATGAACTACCCTCTGCCATA AAGTTTCTAATGGGAAAGGAAGAGACATTTTCGTAAGTTATAGACCAI Hill IATGATATApARBI- 677: SLC38A1_ 2_Exogen ous_56_5ר TAAAGATGTCAAGCTTCAAATCATTATCATAAGGTTAAATATATTACGCATGTCTTTACAGCA AGTTTATTTCTGATCGTGAAAGTAGAAGAAGTCTCACAAACAGCCATTTGGAAAAAAAGAA GTGTGATGAGTATGTAAGTATCATTATAATGAAGTATGCTTATTTTTTTAATCATATAAATTG GGACAAATCI 1 1 1 1AATTCAAGTAGCATAGTACCAAAAGCATAACTACCTGTATTCACCAGG ATATTCCTCATACCTTATGTATTTICTCTTGAAATCCATTCAAGGAAATAACTAGATAACTAA GAATGGATTTTCTTGAATTTTACTTCCATATTGGTTCCTGAGAGTGCATTAAAGGCTTTGGCT TGATGAACTTTCTTGGGGATTATTTTGCTTAGTGTCAATGTTTGTTTCTTTGTTCAGATTCCA GGTACAACCTCCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctg gaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctgg ggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctct atggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCC CGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGG GTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAA CCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1 CGCAACGGGTTTGCCGCCAGAAC ACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGC CGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGC GTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTT GGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTAC GTCTTTGTTTCGTIIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTA GAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGC CCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGG GCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCT 162 WO 2022/093846 PCT/US2021/056689 GCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCT ACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCA GGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTC GAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGC AACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCG ACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCA GCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCT GCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCG CGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAG CTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagca lllllllLaLlgLallLlagllglgglllglLLaaaLlLatcaatgtatcttatl IAGGCAIG ICAG 1 1 1 1 1AACCTA AGCAACGCCATTATGGGCAGTGGGATTTTGGGACTCGCCTTTGCCCTGGCAAACACTGGAA TCCTACI 1 1 1 ILIGIGAGIAI 1 GACG 1GCCGG 1ACI 1ICCAI11 IAAAACIGAACI 1 1 1 1 GTAT Gl 1 ILIGIIAI 1 ALA 1AGAAGAAA1 G 1GAAA1A1 1 1 Al AAAI AG 1 Hill 1ATTAACTTGGCT AAGTTACAAGTACATACTTTGATATTTATTGCTTGAGTGATTTTCCAAACTGTACCTAATGCT TACAACAAAGAGGAAGGAGAAAATCI 1 1 1 1ATTAATCAAAAATACTGAAATAAGCATTTGT GAAAAGGATTAAAACATTTGAAAATAACI 1 1 1 1 1 IGG IAI 1 1 1 1 GGAGTCTACCTGTGACTTT AAATCTCAGTTAAAATATTAAGAGGTGTTTAACCCCAGCCAGTCACCACTTpARBI- 678: SMAD2_1Exogeno us_58 ATCATTCTTCACACTAGTTCCI 1 1 1L1 GACTCTTCAGTCACCTCCAGAATTAATATCCTTAGAA GCATCTCTAAAATGAGTTTGATTTACTAAACATAGAAGTTGACAAAG Hill CAAGTATAAC TGCATAAACTCTCI Illi IAAAAAAICAGI 1 1 1 1 CCCAAGTTGTTAGCCTTTCATTGGCATTTG AGTCATTTATGTGACATATTTATAAGAAACATCTGCTAGTGCTGCTGCATACTTTTATCAGAT CCATTAAATAGTACAI 1 1 1 1 GTTCTTGATTCTCACTAAAACTAACTAAATGGCTGTCATTCTTT TCTTTATGCTTTTATTGTACTAATTTAGCCCATTTGACTGCACllllllllllllllllll AAAGTTCCCT CCTTTCTTTTCCCCTTGCTTCCCAACAGGTCTCTTGATGGTCGTCTCCAGGTATCCCATCGAtg acgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccactcccac tgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggggtggggtggggca ggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctatggGGATCTGCG ATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTTGG GGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGGGA AAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACCGTATATAAGT GCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCAGAACACAGCTGAAGC TTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCGCCATCCACGC CGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGTCCGCCGTCTA GGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTGGAGCCTACCT AGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGTCTTTGTTTCG TIIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGAGCTAGCGAA TTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTC GAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGA TGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCT GGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCAC ATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCA TCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACA CCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGG GGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAA GAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCT CGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAAC CACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATG GTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAatg attgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcat tctagttgtggtttgtccaaactcatcaatgtatcttatAAAGGATTGCCACATGTTATATATTGCCGATTAT GGCGCTGGCCTGATCTTCACAGTCATCATGAACTCAAGGCAATTGAAAACTGCGAATATGC TTTTAATCTTAAAAAGGATGAAGTATGTGTAAACCCTTACCACTATCAGAGAGTTGAGACAC CAGGTAGGAATATTGCAAGTTTTTTTCTTGGTTTTGAATTAAATGCCTGAACTTCAGTATATT TAAGTACTCTTGTGACCCAGGAAAATTTTAGTGTAAATTCTAATAAATTACCTTAAATTGTGC 2541 163 WO 2022/093846 PCT/US2021/056689 ATATTATTTGGTGGTAATTAAAAtttttttatttttaaaaatttttAATGAGAAAACATATCTG 1 1 10 FT GGAATAGCATATGATTTGGCATGAAAGTGCATATCCAGGAAATCCTGTAGATTGGCAGTCT GCTCAGCGCTATGCTGATGTGCTTCTACATGTCCCTpARBI- 679: SMAD22Exogeno us_59 TTCTATATTAAAAATCAGTTGACATCTG Illi 1AGATAAI Illi 1AAAAAACTGGATTATAAA ATGAAGCACTTAGTAAAGCTGATGGCAGAGGTTTTAGATCTTTTGAATACAGGAAAGTGGT AAGGGCATTATAGGTATGATTCATTGAGCTAGAGGGCGTTGGTGTTCACATTTTAAAAACA TAATCATGACTTATCTGGAGTCACATGTTCCATTTTATTGGCTTCCTTCATATAGAAAATATA GTAACCAGCACTACATGCCTGTGAAAAAGTGAAGCAATTGTATATITICTGGGTGAAGGAA GTATTCTGTACATTCTCCATGTTTTACATCATGGTATTTTGAATAACCATGCTTCCATGTTCAC ATCAAI 1 1 1 1 IGI 1 1 1 1CAATTTATGCACAGCACTTGCTCTGAAATTTGGGGACTGAGTACAC CAAATACGATAGATtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgacc ctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattc tggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtggg ctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGT CCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCG GGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAG AACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCAGA ACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAG GCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACT GCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCC CTTGGAG CCTACCTAG ACTCAG CCG G CTCTCCACG CTTTG CCTG ACCCTG CTTG CTCAACTCT ACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTC TAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGT GCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGA GGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAA GCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCC GCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGT CCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAA GTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATG GCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGAC GGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGC TGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAA GCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGAC GAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCAGTGGGATACAACAGGCC TTTACAGCTTCTCTGAACAAACCAGGTGAATATTCTGCCCTCTGTCGAATCTTAGAGATCTTG TG G G AG G G G G GTATATTTTG A AAG ACCTATATG G G GTTG CTTAGTATAATTTTG CCTAG G A TGTTTCCTTAATGTAAAATAAGGCATAGCATTTAAAATATCTGCTTGCCAGTATAAAAAATAT ATTAAATGTTTCAGCTGATGTTTTAATCAATGCAATTCTAGTTTGAATCTTCTTTAAATTACTG TATCCCCTAAAGAATAATAATTTTGATAACTATATATTTATTTTAGCTTGAGATCAGATTATA ATCTGTTGTTGGCCTAAI 1 1 1 1AAGTAGATACATGATGAGTTTTGCTAAATTTCTTGTTATCA GAATCTCATCTTTATACTAATAAATACATACTTAATGAACCCCTTATATCACAA 2541 pARBI- 680:SMAD23Exogeno us_60 TCAATGTAI 1 1 1 IGTATAGTCTI 1 1 GAGATTAGAGTGAAGTTCTAAAAAGTAAGAGAACCTT TTGTGAAAATATTTTAATTGACACTACTAAGAGTTTAAAATAGTATTGGTGGTGAAAAATCG TTAAAAGTATCTGATTTTACTTGCAAAATTACTGTATTTTCCCACAAGAGGAGTCCTTACAAC ATTCTTGI 1 1 1 1AGAAGGGTTTGTTTCCATCATTCATTTAAATTCATAAAGATAACGTTTTCAT GGGTGGAGAAGTCTATTGGGAAAGTCATAATTCGAAI 1 1 LI ATCTTG CTTTG CAGTTTGCTT TCTATGATAAGTTGAAATTATTACTTGATGTTCAAGGTAGTCTCTACATCATCCTTTCAATAT TTCTGCTAGGTTCGATACAAGAGGCTGTTTTCCTAGCGTGGCTTGCTGCCTTTGGTAAGAAC ATGTCGTCCATCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctg gaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctgg ggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctct atggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCC CGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGG 2541 164 WO 2022/093846 PCT/US2021/056689 GTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAA CCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCAGAAC ACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGC CGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGC GTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTT GGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTAC GTCTTTGTTTCGTIIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTA GAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGC CCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGG GCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCT GCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCT ACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCA GGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTC GAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGC AACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCG ACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCA GCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCT GCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCG CGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAG CTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagca tttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTTGCCATTCACGCCGCCAGTTGT GAAGAGACTGCTGGGATGGAAGAAGTCAGCTGGTGGGTCTGGAGGAGCAGGCGGAGGA GAGCAGAATGGGCAGGAAGAAAAGTGGTGTGAGAAAGCAGTGAAAAGTCTGGTGAAGAA GCTAAAGAAAACAGGACGATTAGATGAGCTTGAGAAAGCCATCACCACTCAAAACTGTAAT ACTAAATGTGTTACCATACCAAGGTAAGTTTTGTTAGATCCCAGGTTTGATCAAATTATGTC AAGGAATCTGAAGGAAAGTTACTGAATTTGTGTTCCTTTCAAGTTGCCTGTAAAAAGTGAT GATTGAAATATGACTG Hill AACC1 1G 1A1 AAA 1 1G 1 1 1 1 1GCTAGCTGACTTGTTTTATAA ATTATTTTCTTGAATAGTGAGGTTTAATCAAGCTAAATAAGATACTTAGATTTATTATCTTCApARBI- 681: SOCS1_1Exogeno us_61 GGGCTCCCGCAGCACAGCCI 1 ILICCGGCCCTAGCCCAAATCGCCCAGACCAGGCGCGGAT CCCAGCCTGGCCAGCAGGCGGCGGGCGCGGGGCGGCGAGCCGGGGCCGGACGGCTGGA GCCAGAACCGGCTGCTCTCCACGCCCCCCTCTCGGTGCTGCCCGGAGGCCGGACTCCGCCT CCACCGAGCCCCCACCCGCCGGGAAGAGCTCCGCGGAGTACAGAGCCCATIIICTAGCTGT GTCCACTGAGGCTGAACGGATCCGCGCGGACTTGGTGCTCCGTGCTCGCCCCCTAGGGCCG GGTCCGCCGGGAGCGCCGCCCTCCGGAGTTGTCCGGCCGGCGCACACCTGCCCGGCCCCG CAGCGCCCCAGCTCACCTCTTTGTCTCTCCCGCAGCGCACCCCCGGACGCTATGGCCCACCC CTCCGGCTGGCCCCTTCTGTAGGATGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccc cgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagt aggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgct ggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCAC ATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGA GAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGA GGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGG GTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGC CGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGG TGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTT GTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTG CTTGCTCAACTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGA CCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGT TCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCA GCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCT GCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGT GCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGC CCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCG CGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGA CTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAA 2541 165 WO 2022/093846 PCT/US2021/056689 CGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCAC AACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGC GACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAG ACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCAC TCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatc acaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGTAGCA CACAACCAGGTGGCAGCCGACAATGCAGTCTCCACAGCAGCAGAGCCCCGACGGCGGCCA GAACCTTCCTCCTCTTCCTCCTCCTcgcccgcggcccccgcgcgcccgcggccgtgccccgcggtcccggcccc ggCCCCCGGCGACACGCACTTCCGCACATTCCGTTCGCACGCCGATTACCGGCGCATCACGC GCGCCAGCGCGCTCCTGGACGCCTGCGGATTCTACTGGGGGCCCCTGAGCGTGCACGGGG CGCACGAGCGGCTGCGCGCCGAGCCCGTGGGCACCTTCCTGGTGCGCGACAGCCGCCAGC GGAACTGCI 1 1 1 1CGCCCTTAGCGTGAAGATGGCCTCGGGACCCACGAGCATCCGCGTGCA CTTTCAGGCCGGCCGCTTTCACCTGGATGGCAGCCGCGAGAGCTTCGACTGCCTCTTCGAG CTGCTGpARBI- 682: S0CS12Exogeno us_62 GGATCCCAGCCTGGCCAGCAGGCGGCGGGCGCGGGGCGGCGAGCCGGGGCCGGACGGC TGGAGCCAGAACCGGCTGCTCTCCACGCCCCCCTCTCGGTGCTGCCCGGAGGCCGGACTCC GCCTCCACCGAGCCCCCACCCGCCGGGAAGAGCTCCGCGGAGTACAGAGCCCATTTTCTAG CTGTGTCCACTGAGGCTGAACGGATCCGCGCGGACTTGGTGCTCCGTGCTCGCCCCCTAGG GCCGGGTCCGCCGGGAGCGCCGCCCTCCGGAGTTGTCCGGCCGGCGCACACCTGCCCGGC CCCGCAGCGCCCCAGCTCACCTCTTTGTCTCTCCCGCAGCGCACCCCCGGACGCTATGGCCC ACCCCTCCGGCTGGCCCCTTCTGTAGGATGGTAGCACACAACCAGGTGGCAGCCGACAATG CAGTCTCCACAGCAGCAGAGCCCCGAtgacgactgtgccttctagttgccagccatctgttgtttgcccctccc ccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgag taggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgc tggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCAC ATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGA GAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGA GGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGG GTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGC CGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGG TGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTT GTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTG CTTGCTCAACTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGA CCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGT TCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCA GCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCT GCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGT GCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGC CCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCG CGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGA CTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAA CGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCAC AACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGC GACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAG ACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCAC TCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatc acaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCGGCGG CCAGAACCTTCCTCCTCTTCCTCCTCCTcgcccgcggcccccgcgcgcccgcggccgtgccccgcggtcccgg ccccggCCCCCGGCGACACGCACTTCCGCACATTCCGTTCGCACGCCGATTACCGGCGCATCA CGCGCGCCAGCGCGCTCCTGGACGCCTGCGGATTCTACTGGGGGCCCCTGAGCGTGCACG GGGCGCACGAGCGGCTGCGCGCCGAGCCCGTGGGCACCTTCCTGGTGCGCGACAGCCGCC AGCGGAACTGCI 1 1 1 1CGCCCTTAGCGTGAAGATGGCCTCGGGACCCACGAGCATCCGCGT GCACTTTCAGGCCGGCCGCTTTCACCTGGATGGCAGCCGCGAGAGCTTCGACTGCCTCTTC GAGCTGCTGGAGCACTACGTGGCGGCGCCGCGCCGCATGCTGGGGGCCCCGCTGCGCCAG CGCCGC 2541 166 WO 2022/093846 PCT/US2021/056689 pARBI- 683: S0CS13Exogeno us_63 CGGACTCCGCCTCCACCGAGCCCCCACCCGCCGGGAAGAGCTCCGCGGAGTACAGAGCCC ATTTTCTAGCTGTGTCCACTGAGGCTGAACGGATCCGCGCGGACTTGGTGCTCCGTGCTCGC CCCCTAGGGCCGGGTCCGCCGGGAGCGCCGCCCTCCGGAGTTGTCCGGCCGGCGCACACC TGCCCGGCCCCGCAGCGCCCCAGCTCACCTCTTTGTCTCTCCCGCAGCGCACCCCCGGACGC TATG G CCCACCCCTCCG G CTG G CCCCTTCTGTAG G ATG GTAG C ACACA ACCAG GTG G CAG C CGACAATGCAGTCTCCACAGCAGCAGAGCCCCGACGGCGGCCAGAACCTTCCTCCTCTTCCT CCTCCTcgcccgcggcccccgcgcgcccgcggccgtgccccgcggtcccggccccggCCCCCGGCGACACGCA CTTCCGCACAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctgga aggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctgggg ggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctat ggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCC GAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGG TAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACC GTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGCCGCCAGAACAC AGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCG CCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGT CCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTG GAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGT CTTTGTTTCGTTIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGA GCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCC ATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGC GAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGC CCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTAC CCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGG AGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGA GGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAA CATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGAC AAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGC GTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGC CCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCG ATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCT GTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattt ttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTTCCGTTCGCACGCCGATTACCGGC GCATCACGCGCGCCAGCGCGCTCCTGGACGCCTGCGGATTCTACTGGGGGCCCCTGAGCGT GCACGGGGCGCACGAGCGGCTGCGCGCCGAGCCCGTGGGCACCTTCCTGGTGCGCGACAG CCGCCAGCGGAACTGCI 1 1 1 1CGCCCTTAGCGTGAAGATGGCCTCGGGACCCACGAGCATC CGCGTGCACTTTCAGGCCGGCCGCTTTCACCTGGATGGCAGCCGCGAGAGCTTCGACTGCC TCTTCGAGCTGCTGGAGCACTACGTGGCGGCGCCGCGCCGCATGCTGGGGGCCCCGCTGC GCCAGCGCCGCGTGCGGCCGCTGCAGGAGCTGTGCCGCCAGCGCATCGTGGCCACCGTGG GCCGCGAGAACCTGGCTCGCATCCCCCTCAACCCCGTCCTCCGCGACTACCTGAGCTCCTTC 2541 pARBI- 684: SRP14_1_ Exogenou s_64 GGCAGACAAACAGTTAAAACAGAGGAGTGGGGTAAGTGATGACCTAACCCAGCCCCGCTG CTCTAGTTTTGTTAAACACCTCATCTGCTATCACGGTCTGGCGAAACCCTGGAGAAACTATT ATTTCCACGACGGAAACATGTAATATCGAAGCACGTTAAATTCCACTCAAAGTGGCGGCGT CTGGGATCCCTGACAAAGAGCCCTGGGCTGCTTGGGGCCCATTGTTACCAGAAGCAACCTA GGCGGCTCAGTGCTGGGGACTGAGCCAGCTACAATCCCTACTATTTTCCGGGCCCGAAGCC CCGAATGTGCTCAGTACAGGGTGGGGAAAGGTAGAGGAAGGCGGCGGTCCGCGGCAGAC AGACTCCGGTGGCTCCCAGACACCGGGAACCCAGGGAGCATCGCCCGGCTCCCCTCCCGCT GCTTACACTTCTTCAAGGTGATATAtgacgactgtgccttctagttgccagccatctgttgtttgcccctccccc gtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagta ggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctg gggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACA TCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAG AAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAG GGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGGGT TTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCG 2541 167 WO 2022/093846 PCT/US2021/056689 CCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTG CCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGT CCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCT TGCTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACC GGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTC ACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGC GTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGC ACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGC AGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCC GAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCG CCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACT TCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACG TCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAA CATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGA CGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGAC CCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTC TCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcaca aatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGACGCTGCC CGACGTCCGGCACTTCTGGAAAAGTCTGGTCAGCTCCGTCAGGAACTGGAAAACAACAGGC CCAGCCCCGTTAGCCAGCCCCAAATCCTCGTCCTGCCGCGTCAAGGCCCTGGTCCTCCTGCA GGAGGCACAGGTCTCGAGTAACGCCTGAGCCGCCCCCTTCCCTCGGCCGGCCAGGCCTAGC CATACCTGCTCGCTCTCCAACAACACCATCGCGGCGACGCTGGCTCGACTCCCTCCGCTTAA GCCCCTAGCAGTGAGAGCCGGAAGTTCGGCCTAGGCTGGGCGGGACTTCCGCTACTAGAC TTCCATTGTCTTCCACCAATCTCTTCTCTTCCACCAATCCCGGCCTGCGCCCTCCCCCCTCCCC GCCCGCCTAGCGCCCGCGCCCTGGGACGTCCGGGGGCCTGTGACCCGGAGGCGCTGGGGC TGTCCTGGGTCpARBI- 685: SRP14_2_ Exogenou s_65_66 GTCTGTCTGCCGCGGACCGCCGCCTTCCTCTACCTTTCCCCACCCTGTACTGAGCACATTCGG GGCTTCGGGCCCGGAAAATAGTAGGGATTGTAGCTGGCTCAGTCCCCAGCACTGAGCCGC CTAGGTTGCTTCTGGTAACAATGGGCCCCAAGCAGCCCAGGGCTCTTTGTCAGGGATCCCA GACGCCGCCACTTTGAGTGGAATTTAACGTGCTTCGATATTACATGTTTCCGTCGTGGAAAT AATAGI 1 ILICCAGGGTTTCGCCAGACCGTGATAGCAGATGAGGTGTTTAACAAAACTAGA GCAGCGGGGCTGGGTTAGGTCATCACTTACCCCACTCCTCTGTTTTAACTGTTTGTCTGCCG CTCAGCCACGTACGCGGCCGTGTTCACCAGGATGCATTTTTTCCTTCAGATGACGGTCGAAC CAAACCCATTCCAAAGAAGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttc cttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtca ttctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgc ggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCC ACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTG GCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTGG GGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCC GCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTA CCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCC TGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGG CGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTC AACTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGC CTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGG GGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTC CGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCAC CGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGC TTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAG GCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGA GGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAA GGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTA TATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATC GAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGC 2541 168 WO 2022/093846 PCT/US2021/056689 CCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCA ACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGG CATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaattt cacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGGTACTGTGGAG GGCTTTGAGCCCGCAGACAACAAGTGTCTGTTAAGAGCTACCGATGGGAAGAAGAAGATC AGCACTGTGGTGAGCTTAA1 1 1 LI AAGGCTGTCTTTTGAAATGTAAAGACTTGAACTTAACA GAGGATGGGGCGI 1 ILIGAACCAGGCI 1 1 IAI 1 IGI 1 1 1 1CCCTTTTGCCCTGTGTGGCTATT TTTGAGACCAGGACCTTCCTATACTTTAGTAGTGGAAACCTCAAGAATAAAATAAGAAGGT AGAGGTCAGACAGTCGTTAGTTCTGCTAAAGCTCTTGTGGAAATGAAAGTAGCATATTGGT CCTTATTCGTAGTACTGTAAGGAGCAGCTGGCATAAATATTTGATTCCTTAGCCCCTTACTGT GCTGGGCCTTCAATAAGCAGTTTCTTGGTACCAGGTGATGCTATTATTTCCTTATCTTTGTGG TTCACpARBI- 686: SRSF9_1_ Exogenou s_67 CCCACGTCAGTGAGTGCTCACAAGTCTGTGAGGTAGGCGGCGCCACAGAGAGAAACTGAG GCGCGGGAGCCCAAGCCACTTGTCCAGCGCCTCAGCCGAGCGCGAACCGCGCTCGGGGAT GGCATCCACACGGCCCGGCCCCAGGCTCTCCCTGTCAGCGCCCGAAGGCCCTTCGCACCTC CAGGGGGCGCCGGCCTGCGCGCACGCGCAATGGTCGCAGCCGCGTTCTCTTTAAGAGGAC TCCTTTTGCCTCCGCCGACCCCTTCGCTTCCGCTCCGCGTTCCCACAATGCAGTGCGGCTGAG CGCCTCGGAGCCCGCGGGGACGCTGCGGGGGGACCCGTGCTGAggcggcggcggcgacgtgggc tgcggcgggcccgcggcgtcgggcggtgcggatgtcgggctgggcggacgagcgcggcggcgAGGGCGACGGG CGCATCTACtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaa ggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggg gtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctatg gGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCG AGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGGT AAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACC GTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCAGAACAC AGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCG CCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGT CCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTG GAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGT CTTTGTTTCGTTIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGA GCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCC ATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGC GAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGC CCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTAC CCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGG AGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGA GGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAA CATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGAC AAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGC GTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGC CCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCG ATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCT GTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattt ttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGTGGGGAACCTTCCGACCGACGTG CGCGAGAAGGACTTGGAGGACCTGTTCTACAAGTACGGCCGCATCCGCGAGATCGAGCTC AAGAACCGGCACGGCCTCGTGCCCTTCGCCTTCGTGCGCTTCGAGGACCCCCGGTGAGGccc ccgcgcccctgccctctcctcctcggtgcctgaggcccccgccttccctgctgtcccctcccccagggctcccctccccccg gcctcccctccccccgcctccgcgcagacccctcaCGGCGCCCCCTCACGGGTGGAGGATGAGGCAGCC TCTCCTCGCAGGCCCGGGCCGTCCTTCGCGCCGTCGTCACTTCCTTTAI 1 1 1 IATTATTCCAAT ATTTTACTTAG AAACCC AAAAG CTG AG CCTTTG G AG G G CCCAAG CCCG CCTG CACCG G CCT CGGGGGGTCCAAATGAGCCTTGTCCGCC 2541 pARBI- 687: SRSF9_2_ TGTGGTGTGCTTTTCGAGAAAATGCTCACGAAGATTAGAAAAACACTGATGGTTTATTGGC AAAATCAATAATCTGTCAGCAGTTGATTCttttttttEFCTGAATTAGCCCTCTTATGAGTAATCT GTTTGCTCATTCATTATAATTTCATACCTCTAAAACTGCGTGTGACAGCTGTAAAGGTTAATT 2541 169 WO 2022/093846 PCT/US2021/056689 Exogenou s_68CCAGTATCATGAAACGTCTCCAAACCAAAGCAGAAGTGCTTCAGGATCCTGATTTGTGTGTT Illi 1CTTCACTCTAGGTTTCCCTTTTATGCTTACTACTCATGCCCCTCACTTGGAAAGTCACT TGGCCTCCTGAACAGCACTAACTCCAAACGttttttttgttgttgttgttttttttAGAGATGCAGAGGA TGCTATTTATGGAAGAAATGGTTATGATTATGGCCAGTGTCGGCTTCGTGTGGAGTTCCCCA GGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccact cccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggggtggggtgg ggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctatggGGATCT GCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTT GGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGG GAAAGTGATGTCGTGTACTGGCTCCGCC1 1 1 1 1CCCGAGGGTGGGGGAGAACCGTATATAA GTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCAGAACACAGCTGAA GCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCGCCATCCAC GCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGTCCGCCGTC TAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTGGAGCCTAC CTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGTCTTTGTTT CGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGAGCTAGCG AATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGG TCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGC GATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGC CCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGAC CACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCA CCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCG ACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCC TGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCA GAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCA GCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGAC AACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACA TGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAA atgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactg cattctagttgtggtttgtccaaactcatcaatgtatcttatACTTATGGAGGTCGGGGTGGGTGGCCCCGT GGTGGGAGGAATGGGCCTCCTACAAGAAGATCTGATTTCCGAGTTCTTGTTTCAGGTATGT TCCTTTCAAACAGaatgagatgatacatgtaaaatacttaacacagagtctgtcttccaagaaatgatagctgttat tcttCAGTGCATGGGACACGGGGGCTTTCTTTTCAATAGCCTGTGTGAAGCCTTGCCCTGGAT TGCCAATGAGGAAAGTATCCTGCAAATGAAATTGCGCTGGGAGTGCAGCCTTGGAAGAAC ATAACCATATTTCTTGTAAAGGAGTTIICTAGTGGTGAGAAGGAAAGATGATGGGAAAACT TGAGCTACAATTCTAAAGATGCTTCTTTTGGAATATACTTGGCATCAGACATGGTAGAAAGG CATTCAAGGAGCCAGATTTGAACAACTTACCCAGCCpARBI- 688: SRSF9_3_ Exogenou s_69 GATGGCATCCACACGGCCCGGCCCCAGGCTCTCCCTGTCAGCGCCCGAAGGCCCTTCGCAC CTCCAGGGGGCGCCGGCCTGCGCGCACGCGCAATGGTCGCAGCCGCGTTCTCTTTAAGAG GACTCCTTTTGCCTCCGCCGACCCCTTCGCTTCCGCTCCGCGTTCCCACAATGCAGTGCGGCT GAGCGCCTCGGAGCCCGCGGGGACGCTGCGGGGGGACCCGTGCTGAggcggcggcggcgacgt gggctgcggcgggcccgcggcgtcgggcggtgcggatgtcgggctgggcggacgagcgcggcggcgAGGGCGAC GGGCGCATCTACGTGGGGAACCTTCCGACCGACGTGCGCGAGAAGGACTTGGAGGACCTG TTCTACAAGTACGGCCGCATCCGCGAGATCGAGCTCAAGAACCGGCACGGCCTCGTGCCCT TCGCCTTCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaagg tgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggggt ggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctatgg GGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCGA GAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGGTA AACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACCGT ATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCAGAACACA GCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCGC CATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGTC CGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTGG AGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGTC 2541 170 WO 2022/093846 PCT/US2021/056689 1 1 IGI ITCGI 1 1 ILIGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGAG CTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCA TCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCG AGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCC CGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACC CCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGA GCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAG GGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAAC ATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACA AGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCG TGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCC CGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGA TCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTG TACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattttt ttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGTGCGCTTCGAGGACCCCCGGTGAG Gcccccgcgcccctgccctctcctcctcggtgcctgaggcccccgccttccctgctgtcccctcccccagggctcccctccc cccggcctcccctccccccgcctccgcgcagacccctcaCGGCGCCCCCTCACGGGTGGAGGATGAGGCA GCCTCTCCTCGCAGGCCCGGGCCGTCCTTCGCGCCGTCGTCACTTCCTTTA 1 1 1 1 IATTATTC CAATATTTTACTTAGAAACCCAAAAGCTGAGCCTTTGGAGGGCCCAAGCCCGCCTGCACCG GCCTCGGGGGGTCCAAATGAGCCTTGTCCGCCTCCTGCCTGGGGCAGCACCGTAGGGGGA AGCGGCCGCGGGGCAGCGCGGGGGTCGCCGTTCGCCCTTCCCGCTCGCCTCTCCCCCGGCC CGTG CTCG CCGTGG CTG G AG AGCAAGCTpARBI- 689: SUB1_1_ Exogenou s_70 GTAACTGACTAGCCTTAGTAGACTGTGGTTTCCAGGTTTATTCAGAAGTAGCAAGATCCCTC CAtttttttttefACCAAAGAAATCGTATGTGGGATCCCAAACCACAAAATAACCGTTCCTGTGG TTAATACTACTATAATGCCTGAAGTGTCTTTTGGGATCCTGAGAACAGAGTTTGAAAACATT ACTAGACAGAAGGATTGGTTAGATTCATAGTTTTGTTGTTGAGTGAAACTTGCTTATGTATA TATTTATGATATTTTGGATGTAGTCTTTTGATTGTTTAAATCTTAAAAAGTAATGGGATCTTT TGACACTGGGGTATGTTTTA1 1 1 1 1A1G 1G 1GCAAA Illi AACCA1A1 1 C1 1 1 1L1AGTTAAA GAGGAAAAAGCAAGTTGCTCCAGAAAAACCTGTAAAGAAACAAAAGACAGGTGAGACTTC GAGAGCCCTGTCAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccc tggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattct ggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggc tctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTC CCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGG GGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGA ACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1 CGCAACGGGTTTGCCGCCAGAA CACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGG CCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTG CGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCC TTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTA CGTCTTTGTTTCGTTTICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCT AGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGT GCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGA GGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAA GCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCC GCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGT CCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAA GTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATG GCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGAC GGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGC TGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAA GCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGAC GAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcaLLLLLLLcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTCTTCTAAACAGAGCAGCA 2541 171 WO 2022/093846 PCT/US2021/056689 GCAGCAGAGATGATAACATGTTTCAGGTAAAGTTGGCTALLLLLLLLLLLLLLLLLLLLgacatggagtcat gctctgtcacccaggctggagtgcagtggcgccatctcggctcactgcaacctcagcctcctgagttcaagcagttctctg cctcagcctcccgagtagctaggattacaggcatccgccaccagacctggctaatttttgtatttttagtagagatggggt ttcaccatcttggccaggctggtcttgaactcctgaccttgtgatccaactgcctcagcctccaaaagtgctgggtttacag gtgtgagccaccatgccttgccAAAGTTGGCTGTTTCTTTAGATTCAGAGGAATTATTATCTGGCTT GATCTGAAGAATGTTAAAAGTACTATGATCTGATAATTGCCTAATATGpARBI- 690: SUB1_2_ Exogenou s_71 ATAAATAAACATATCCTGGAAATGGAATAAGTTGGTTATATTCI 1 1 1 1AATTAGTATATCTGC TTCGTAAAATAAGTAACTGACTAGCCTTAGTAGACTGTGGTTTCCAGGTTTATTCAGAAGTA GCAAGATCCCTCCAI 1 1 1 1 1 1 1 1 LI ACCAAAGAAATCGTATGTGGGATCCCAAACCACAAAAT AACCGTTCCTGTGGTTAATACTACTATAATGCCTGAAGTGTCTTTTGGGATCCTGAGAACAG AGTTTGAAAACATTACTAGACAGAAGGATTGGTTAGATTCATAGTTTTGTTGTTGAGTGAAA CTTGCTTATGTATATATTTATGATATTTTGGATGTAGTCTTTTGATTGTTTAAATCTTAAAAAG TAATGGGATCTTTTGACACTGGGGTATGTTTTAI 1 1 1 1ATGTGTGCAAATTTTAACCATATTC 1 ili AGTTAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctgga aggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctgggg ggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctat ggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCC GAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGCGGGG TAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGAGAACC GTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCAGAACAC AGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTGAGGCCG CCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGT CCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCTCCCTTG GAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACTCTACGT CTTTGTTTCGTTIICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTACTCTAGA GCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCC ATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGC GAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGC CCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTAC CCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGG AGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGA GGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAA CATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGAC AAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGC GTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGC CCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCG ATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCT GTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcattt ttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatAAGAGGAAAAAGCAAGTTGCTCCA GAAAAACCTGTAAAGAAACAAAAGACAGGTGAGACTTCGAGAGCCCTGTCATCTTCTAAAC AGAGCAGCAGCAGCAGAGATGATAACATGTTTCAGGTAAAGTTGGCTAI 1 1 1 1 1 1 1 1 1 1 1 1 TTTTTTGACATGGAGTCATGCTCTGTCACCCAGGCTGGAGTGCAGTGGCGCCATCTCGGCTC ACTGCAACCTCAGCCTCCTGAGTTCAAGCAGTTCTCTGCCTCAGCCTCCCGAGTAGCTAGGA TTACAGGCATCCGCCACCAGACCTGGCTAAI 1 1 1 1G 1A1 1 1 1 1AGTAGAGATGGGGTTTCAC CATCTTGGCCAGGCTGGTCTTGAACTCCTGACCTTGTGATCCAACTGCCTCAGCCTCCAAAA GTGCTGGGTTTACAGGTGTGAGCCACCATGCCTTGCCAAAGTTGGCTGTTTCTTT 2541 pARBI- 691: SUB1_3_ Exogenou s_72 AATTAGTATATCTGCTTCGTAAAATAAGTAACTGACTAGCCTTAGTAGACTGTGGTTTCCAG GTTTATTCAGAAGTAGCAAGATCCCTCCATTTTTTTTTCTACCAAAGAAATCGTATGTGGGAT CCCAAACCACAAAATAACCGTTCCTGTG GTTAATACTACTATAATG CCTG AAGTGTCTTTTG GGATCCTGAGAACAGAGTTTGAAAACATTACTAGACAGAAGGATTGGTTAGATTCATAGTT TTGTTGTTGAGTGAAACTTGCTTATGTATATATTTATGATATTTTGGATGTAGTCTTTTGATT GTTTAAATCTTAAAAAGTAATGGGATCTTTTGACACTGGGGTATGTTTTAI 1 1 1 IATGTGTGC AAATTTTAACCATATTCTITICTAGTTAAAGAGGAAAAAGCAAGTTGCTCCAGAAAAACCTG TAAAGAAACAAAAGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgac cctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctatt 2541 172 WO 2022/093846 PCT/US2021/056689 2541 ctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgg gctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAG TCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGCGC GGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGGGA GAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGCCA GAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCTG AGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAA CTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCGCT CCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAACT CTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCTAC TCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTG GTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGC GAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGC AAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCA GCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTA CGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTG AAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAG G ACG G CAACATCCTG G G G CAC AAG CTG G AGTACAACTACAAC AG CCAC AACGTCTATATCA TGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGG ACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGT GCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAG AAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGG ACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaat aaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatACAGGTGAGACTTCGAG AGCCCTGTCATCTTCTAAACAGAGCAGCAGCAGCAGAGATGATAACATGTTTCAGGTAAAG TTGGCTAI 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1GACATGGAGTCATGCTCTGTCACCCAGGCTGGAGTGC AGTGGCGCCATCTCGGCTCACTGCAACCTCAGCCTCCTGAGTTCAAGCAGTTCTCTGCCTCA GCCTCCCGAGTAGCTAGGATTACAGGCATCCGCCACCAGACCTGGCTAAI 1 1 1 1 G 1A1 1 1 1 AGTAGAGATGGGGTTTCACCATCTTGGCCAGGCTGGTCTTGAACTCCTGACCTTGTGATCCA ACTGCCTCAGCCTCCAAAAGTGCTGGGTTTACAGGTGTGAGCCACCATGCCTTGCCAAAGTT GGCTGTTTCTTTAGATTCAGAGGAATTATTATCTGGCTTGATCTGAAGAATGTTAAAAGTpARBI- 692: TET21Exogenous CACAI 1 1 I'AAI 1 1 1 1 G TTTCCATGCTC 1 1 1AGAATTCAACTAGAGGGCAGCCTTGTGGATGGC CCCGAAGCAAGCCTGATGGAACAGGATAGAACCAACCATGTTGAGGGCAACAGACTAAGT CCATTCCTGATACCATCACCTCCCATTTGCCAGACAGAACCTCTGGCTACAAAGCTCCAGAA TGGAAGCCCACTGCCTGAGAGAGCTCATCCAGAAGTAAATGGAGACACCAAGTGGCACTCT TTCAAAAGTTATTATGGAATACCCTGTATGAAGGGAAGCCAGAATAGTCGTGTGAGTCCTG ACTTTACACAAGAAAGTAGAGGGTATTCCAAGTGTTTGCAAAATGGAGGAATAAAACGCAC AGTTAGTGAACCTTCTCTCTCTGGGCTCCTTCAGATCAAGAAATTGAAACAAGACCAAAAGG CTAATGGAGAAAGACGTAACtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgcct tccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtc attctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggat gcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGG TGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTG GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGC CGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCT ACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCG GCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGC TCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGC GCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA 173 WO 2022/093846 PCT/US2021/056689 GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA AG G AG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTTCGGGGTAAG CCAAGAAAGAAATCCAGGTGAAAGCAGTCAACCAAATGTCTCCGATTTGAGTGATAAGAAA GAATCTGTGAGTTCTGTAGCCCAAGAAAATGCAGTTAAAGATTTCACCAG 1 1 1 1 ICAACACA TAACTGCAGTGGGCCTGAAAATCCAGAGCTTCAGATTCTGAATGAGCAGGAGGGGAAAAG TGCTAATTACCATGACAAGAACATTGTATTACTTAAAAACAAGGCAGTGCTAATGCCTAATG GTGCTACAGI 1 ILIGCCTCTTCCGTGGAACACACACATGGTGAACTCCTGGAAAAAACACTG TCTCAATATTATCCAGATTGTGTTTCCATTGCGGTGCAGAAAACCACATCTCACATAAATGCC ATTAACAGTCAG G CTACTAATG AGTTGTCCTGTG AG ATCACTCACCCATCG CATACCTCAG G GCAGATCpARBI- 693: TET22Exogenous _74 AATGGAGAAAGACGTAACTTCGGGGTAAGCCAAGAAAGAAATCCAGGTGAAAGCAGTCAA CCAAATGTCTCCGATTTGAGTGATAAGAAAGAATCTGTGAGTTCTGTAGCCCAAGAAAATG CAGTTAAAGATTTCACCAG 1 1 1 1 1 CAACACATAACTGCAGTGGGCCTGAAAATCCAGAGCTT CAGATTCTGAATGAGCAGGAGGGGAAAAGTGCTAATTACCATGACAAGAACATTGTATTAC TTAAAAACAAGG CAGTG CTAATG CCTAATG GTG CTACAGTTTCTG CCTCTTCCGTG G AAC AC ACACATGGTGAACTCCTGGAAAAAACACTGTCTCAATATTATCCAGATTGTGTTTCCATTGC GGTGCAGAAAACCACATCTCACATAAATGCCATTAACAGTCAGGCTACTAATGAGTTGTCCT GTGAGATCACTCACCCATCGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgcctt ccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtc attctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggat gcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGG TGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTG GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGC CGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCT ACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTC CTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCG GCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGC TCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGC GCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA AG GAG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatCATACCTCAGGG CAGATCAATTCCGCACAGACCTCTAACTCTGAGCTGCCTCCAAAGCCAGCTGCAGTGGTGA GTGAGGCCTGTGATGCTGATGATGCTGATAATGCCAGTAAACTAGCTGCAATGCTAAATAC CTGTTCCTTTCAGAAACCAGAACAACTACAACAACAAAAATCAG Hill GAGATATGCCCAT CTCCTGCAGAAAATAACATCCAGGGAACCACAAAGCTAGCGTCTGGTGAAGAATTCTGTTC AGGTTCCAGCAGCAATTTGCAAGCTCCTGGTGGCAGCTCTGAACGGTATTTAAAACAAAAT 2541 174 WO 2022/093846 PCT/US2021/056689 G AAATG AATG GTG CTTACTTCAAG CA AAG CTCAGTGTTCACTAAG G ATTCCTTTTCTG CC AC TACCACACCACCACCACCATCACAATTGCTTCI 1 ILICCCCCTCCTCCTCTTCCACAGGTTCCT CAGCTTpARBI- 694: TET23E xogenous _75 GGAAAAAGCACTCTGAATGGTGGAGTTTTAGAAGAACACCACCACTACCCCAACCAAAGTA ACACAACACTTTTAAGGGAAGTGAAAATAGAGGGTAAACCTGAGGCACCACCTTCCCAGAG TCCTAATCCATCTACACATGTATGCAGCCCTTCTCCGATGC HILI GAAAGGCCTCAGAATAA TTGTGTGAACAGGAATGACATACAGACTGCAGGGACAATGACTGTTCCATTGTGTTCTGAG AAAACAAGACCAATGTCAGAACACCTCAAGCATAACCCACCAAI 1 1 1 1GGTAGCAGTGGAG AGCTACAGGACAACTGCCAGCAGTTGATGAGAAACAAAGAGCAAGAGATTCTGAAGGGTC GAGACAAGGAGCAAACACGAGATCTTGTGCCCCCAACACAGCACTATCTGAAACCAGGAT GGATTGAATTGAAGGCCCCTCGTtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgt gccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtag gtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgg ggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACAT CGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGA AGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAG GGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGGGT TTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCG CCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTG CCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGT CCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCT TGCTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACC GGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTC ACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGC GTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGC ACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGC AGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCC GAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCG CCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACT TCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACG TCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAA CATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGA CGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGAC CCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTC TCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcaca aatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTTTCACCAA GCGGAATCCCATCTAAAACGTAATGAGGCATCACTGCCATCAATTCTTCAGTATCAACCCAA TCTCTCCAATCAAATGACCTCCAAACAATACACTGGAAATTCCAACATGCCTGGGGGGCTCC CAAGGCAAGCTTACACCCAGAAAACAACACAGCTGGAGCACAAGTCACAAATGTACCAAGT TGAAATGAATCAAGGGCAGTCCCAAGGTACAGTGGACCAACATCTCCAGTTCCAAAAACCC TCACACCAGGTG CACTTCTCCAAAACAG ACCATTTACCAAAAG CTCATGTG CAGTCACTGTG TGGCACTAGATTTCATTTTCAACAAAGAGCAGATTCCCAAACTGAAAAACTTATGTCCCCAG TGTTGAAACAGCACTTGAATCAACAGGCTTCAGAGACTGAGCCATTTTCAAACTCACACCTT TTGCAACAT 2541 pARBI- 695: TIGIT_1_E xogenous _76 AAAGGGAGGTTGAGATGGGCTGAGGTCTTCTAGGAGGCGGGGAGGGAGTGCAGCCTTGA CAAGCCTCCCTGTGGGCGAGGTGTAAAGAGGGGCAGAAGTCAGCTCTGGAAGCATAGGGC AGTGGGTGGGGAGGAGATGGGCTGGGCTGGGCTGGAGTAGAGATGTGTGGAGAAGGGT GAGAAGACTGGAAAGACAACCTGAATGGGGGACTGGGAGCCTTGAATAACAGGCATGGA GAGGAGCGTCTCTTGAAATGGAAGAAACAGGAAATAATTACAGCCTCTATGGAGGAGCAA CAGGATGGACTGGAGAAACTATCATTCCAAAATCCAGTTGGGGCCTCAAAGGCCCTTAGAA Hill CTAGGAAGGTTGAAGGCCAGCTGCTGACCCAGGACTCACATGTGCTTCGTCCTCTTC CCTAGGAATGATGACAGGCACAATAGAAACAtgacgactgtgccttctagttgccagccatctgttgtttgc ccctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcatt gtctgagtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagca ggcatgctggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGA 2541 175 WO 2022/093846 PCT/US2021/056689 GCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTG CCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCTTT TTCCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICG CAACGGGTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGC GCCCGCCGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGC CTGTGGTGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCG GGCCTTTGTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCT GACCCTGCTTGCTCAACTCTACGTCTTTGTTTCGTTITCTGTTCTGCGCCGTTACAGATCCAA GCTGTGACCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAG GAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCAC AAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAG TTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTA CGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCC GCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACA AGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGG GCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACA GCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGAT CCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCC ATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGA GCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCG GGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagc aatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatctta tACGGGGAACATTTCTGCAGAGAAAGGTGGCTCTATCATCTTACAATGTCACCTCTCCTCCA CCACGGCACAAGTGACCCAGGTCAACTGGGAGCAGCAGGACCAGCTTCTGGCCATTTGTAA TGCTGACTTGGGGTGGCACATCTCCCCATCCTTCAAGGATCGAGTGGCCCCAGGTCCCGGC CTGGGCCTCACCCTCCAGTCGCTGACCGTGAACGATACAGGGGAGTACTTCTGCATCTATCA CACCTACCCTGATGGGACGTACACTGGGAGAATCTTCCTGGAGGTCCTAGAAAGCTCAGGT ATTCCTGCTGGAGCAAGTTGGTGGATAAACCTCTCCCTCTAGCATAGAAAATGCAATCCTGA AACACTGCACAGCAGGGCTTCTCAATTCGGGATCACATTTGAATCACCTGAGGAGATTTTAA ATCATACTGATGCCGAGGCCpARBI- 696:TIGIT_2_E xogenous GAGGAGATGGGCTGGGCTGGGCTGGAGTAGAGATGTGTGGAGAAGGGTGAGAAGACTG GAAAGACAACCTGAATGGGGGACTGGGAGCCTTGAATAACAGGCATGGAGAGGAGCGTC TCTTGAAATGGAAGAAACAGGAAATAATTACAGCCTCTATGGAGGAGCAACAGGATGGAC TGGAGAAACTATCATTCCAAAATCCAGTTGGGGCCTCAAAGGCCCTTAGAATTTIICTAGGA AGGTTGAAGGCCAGCTGCTGACCCAGGACTCACATGTGCTTCGTCCTCTTCCCTAGGAATG ATGACAGGCACAATAGAAACAACGGGGAACAI 1 ILIGCAGAGAAAGGTGGCTCTATCATCT TACAATGTCACCTCTCCTCCACCACGGCACAAGTGACCCAGGTCAACTGGGAGCAGCAGGA CCAGCTTCTGGCCATTTGTAATGCTGACtgacgactgtgccttctagttgccagccatctgttgtttgcccctc ccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctg agtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcat gctggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGC ACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAG AGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCG AGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC 1 1 1 1 ICGCAACG GGTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCG CCGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTG GTGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCT TTGTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCC TGCTTGCTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGT GACCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCT GTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTT CAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCAT CTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGC GTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCAT GCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACC 2541 176 WO 2022/093846 PCT/US2021/056689 CGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATC GACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCAC AACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCC ACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCG GCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAA AGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGAT CACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatag catcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTTG GGGTGGCACATCTCCCCATCCTTCAAGGATCGAGTGGCCCCAGGTCCCGGCCTGGGCCTCA CCCTCCAGTCGCTGACCGTGAACGATACAGGGGAGTACTTCTGCATCTATCACACCTACCCT GATGGGACGTACACTGGGAGAATCTTCCTGGAGGTCCTAGAAAGCTCAGGTATTCCTGCTG GAGCAAGTTGGTGGATAAACCTCTCCCTCTAGCATAGAAAATGCAATCCTGAAACACTGCA CAGCAGGGCTTCTCAATTCGGGATCACATTTGAATCACCTGAGGAGATTTTAAATCATACTG ATGCCGAGGCCTCACCCAGACCAATTCAATCAGAATCCCTAATAGCAGAGCTAAACAAGGG TAAGGTCTAAAAGCATTTCCAGGTGATTCTAATGGGCAGCCAATACTGAGAACCACTGTTCT TATGTAAGAAGCACATCpARBI- 697: TIGIT3Exogenous _78 CCTCCCTGTGGGCGAGGTGTAAAGAGGGGCAGAAGTCAGCTCTGGAAGCATAGGGCAGT GGGTGGGGAGGAGATGGGCTGGGCTGGGCTGGAGTAGAGATGTGTGGAGAAGGGTGAG AAGACTGGAAAGACAACCTGAATGGGGGACTGGGAGCCTTGAATAACAGGCATGGAGAG GAGCGTCTCTTGAAATGGAAGAAACAGGAAATAATTACAGCCTCTATGGAGGAGCAACAG GATGGACTGGAGAAACTATCATTCCAAAATCCAGTTGGGGCCTCAAAGGCCCTTAGAATTT TTCTAGGAAGGTTGAAGGCCAGCTGCTGACCCAGGACTCACATGTGCTTCGTCCTCTTCCCT AGGAATGATGACAGGCACAATAGAAACAACGGGGAACATTTCTGCAGAGAAAGGTGGCTC TATCATCTTACAATGTCACCTCTCCTCCACCtgacgactgtgccttctagttgccagccatctgttgtttgccc ctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgt ctgagtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcagg catgctggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGC GCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCT AGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 IC CCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAA CGGGTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCC CGCCGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTG TGGTGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGC CTTTGTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGAC CCTGCTTGCTCAACTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCT GTGACCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAG CTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAG TTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTC ATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGG CGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCA TGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGAC CCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCAT CGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCA CAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGC CACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCG GCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAA AGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGAT CACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatag catcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatACG GCACAAGTGACCCAGGTCAACTGGGAGCAGCAGGACCAGCTTCTGGCCATTTGTAATGCTG ACTTGGGGTGGCACATCTCCCCATCCTTCAAGGATCGAGTGGCCCCAGGTCCCGGCCTGGG CCTCACCCTCCAGTCGCTGACCGTGAACGATACAGGGGAGTACTTCTGCATCTATCACACCT ACCCTGATGGGACGTACACTGGGAGAATCTTCCTGGAGGTCCTAGAAAGCTCAGGTATTCC TGCTGGAGCAAGTTGGTGGATAAACCTCTCCCTCTAGCATAGAAAATGCAATCCTGAAACA CTGCACAGCAGGGCTTCTCAATTCGGGATCACATTTGAATCACCTGAGGAGATTTTAAATCA 2541 177 WO 2022/093846 PCT/US2021/056689 TACTGATGCCGAGGCCTCACCCAGACCAATTCAATCAGAATCCCTAATAGCAGAGCTAAAC AAGGGTAAGGTCTAAAAGpARBI- 698: TRAC_1_ Exogenou s_79 TAATG CCCAG CCTAAGTTG G G G AG ACCACTCCAG ATTCCAAG ATGTACAGTTTG CTTTG CTG GGCCI 1 1 1 1 CCCATGCCTGCCTTTACTCTGCCAGAGTTATATTGCTGGGGTTTTGAAGAAGAT CCTATTAAATAAAAGAATAAGCAGTATTATTAAGTAGCCCTGCATTTCAGGTTTCCTTGAGT GGCAGGCCAGGCCTGGCCGTGAACGTTCACTGAAATCATGGCCTCTTGGCCAAGATTGATA GCTTGTGCCTGTCCCTGAGTCCCAGTCCATCACGAGCAGCTGG1 1 ILIAAGATGCTATTTCC CGTATAAAGCATGAGACCGTGACTTGCCAGCCCCACAGAGCCCCGCCCTTGTCCATCACTG GCATCTGGACTCCAGCCTGGGTTGGGGCAAAGAGGGAAATGAGATCATGTCCTAACCCTG ATCCTCTTGTCCCACAGATtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttcc ttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcatt ctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcg gtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCA CAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGG CGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGG GGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCG CCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACC TGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatATCCAGAACCCTGACC CTGCCGTGTACCAGCTGAGAGACTCTAAATCCAGTGACAAGTCTGTCTGCCTATTCACCGAT TTTGATTCTCAAACAAATGTGTCACAAAGTAAGGATTCTGATGTGTATATCACAGACAAAAC TGTGCTAGACATGAGGTCTATGGACTTCAAGAGCAACAGTGCTGTGGCCTGGAGCAACAAA TCTGACTTTGCATGTGCAAACGCCTTCAACAACAGCATTATTCCAGAAGACACCTTCTTCCCC AG CCCAG GTAAG G G CAG CTTTG GTG CCTTCG CAG G CTGTTTCCTTG CTTCAG G A ATG G CCA GGTTCTGCCCAGAGCTCTGGTCAATGATGTCTAAAACTCCTCTGATTGGTGGTCTCGGCCTT ATCCATTGCCACCAAAACCCTC1 1 1 1 1ACTAAGAAACAGTGAGCCTTGTTCTGGCAGTCCAG A 2541 pARBI- 699: TRAC_2_ Exogenou s_80 GATTCCAAGATGTACAG 1 1 IGCITTGCTGGGCCI 1 1 1 1 CCCATGCCTGCC1 1 IACTCTGCCAG AGTTATATTGCTGGGGTTTTGAAGAAGATCCTATTAAATAAAAGAATAAGCAGTATTATTAA GTAGCCCTGCATTTCAGGTTTCCTTGAGTGGCAGGCCAGGCCTGGCCGTGAACGTTCACTG AAATCATGGCCTCTTGGCCAAGATTGATAGCTTGTGCCTGTCCCTGAGTCCCAGTCCATCAC GAGCAGCTGGTTTCTAAGATGCTATTTCCCGTATAAAGCATGAGACCGTGACTTGCCAGCCC CACAGAGCCCCGCCCTTGTCCATCACTGGCATCTGGACTCCAGCCTGGGTTGGGGCAAAGA GGGAAATGAGATCATGTCCTAACCCTGATCCTCTTGTCCCACAGATATCCAGAACCCTGACC CTGCCGTGTACCAGCTGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttcctt gaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattc tattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcgg tgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCAC AGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGGC 2541 178 WO 2022/093846 PCT/US2021/056689 GCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGGG GAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCGC CAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACCT GAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatAGAGACTCTAAATCC AGTGACAAGTCTGTCTGCCTATTCACCGATTTTGATTCTCAAACAAATGTGTCACAAAGTAA GGATTCTGATGTGTATATCACAGACAAAACTGTGCTAGACATGAGGTCTATGGACTTCAAG AGCAACAGTGCTGTGGCCTGGAGCAACAAATCTGACTTTGCATGTGCAAACGCCTTCAACA ACAGCATTATTCCAGAAGACACCTTCTTCCCCAGCCCAGGTAAGGGCAGCTTTGGTGCCTTC GCAGGCTGTTTCCTTGCTTCAGGAATGGCCAGGTTCTGCCCAGAGCTCTGGTCAATGATGTC TAAAACTCCTCTGATTGGTGGTCTCGGCCTTATCCATTGCCACCAAAACCCTCI 1 1 1 IACTAA G AAACAGTG AG CCTTGTTCTG GCAGTCCAG AGAATG ACACGG G AAAAAAG CAG ATG AAG A GAAGpARBI- 700: TRAC_3_ Exogenou s_81 TTCCTGTGGTAGCGGAACTCACTAAGGGGCCCATCTGGACCCGAGGTATTGTGATGATAAA TTCTGAGCACCTACCCCATCCCCAGAAGGGCTCAGAAATAAAATAAGAGCCAAGTCTAGTC GGTGTTTCCTGTCTTGAAACACAATACTGTTGGCCCTGGAAGAATGCACAGAATCTGTTTGT AAGGGGATATGCACAGAAGCTGCAAGGGACAGGAGGTGCAGGAGCTGCAGGCCTCCCCC ACCCAGCCTGCTCTGCCTTGGGGAAAACCGTGGGTGTGTCCTGCAGGCCATGCAGGCCTGG GACATGCAAGCCCATAACCGCTGTGGCCTCTTGGTTTTACAGATACGAACCTAAACTTTCAA AACCTGTCAGTGATTGGGTTCCGAATCCTCCTCCTGAAAGTGGCCGGGTTTAATCTGCTCAT GACGCTGCGGCTGTGGTCCAGCtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtg ccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggt gtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgggg atgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCG CCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAG GTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGT GGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTG CCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCC TACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCT CCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCC GGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTG CTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGG CGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA 2541 179 WO 2022/093846 PCT/US2021/056689 AG G AG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTGAGGTGAGGG GCCTTGAAGCTGGGAGTGGGGTTTAGGGACGCGGGTCTCTGGGTGCATCCTAAGCTCTGA GAGCAAACCTCCCTGCAGGGTCTTGCTTTTAAGTCCAAAGCCTGAGCCCACCAAACTCTCCT ACTTCTTCCTGTTAC AAATTCCTCTTGTG CAATAATAATG G CCTG AAACG CTGTAA AATATCC TCATTTCAGCCGCCTCAGTTGCACTTCTCCCCTATGAGGTAGGAAGAACAGTTGTTTAGAAA CGAAGAAACTGAGGCCCCACAGCTAATGAGTGGAGGAAGAGAGACACTTGTGTACACCAC ATGCCTTGTGTTGTACTTCTCTCACCGTGTAACCTCCTCATGTCCTCTCTCCCCAGTACGGCTC TCTTAGCTCAGTAGAAAGAAGACATTACACTCATATTACACCCCAATCCTGGCTAGAGTCTCCGCACCpARBI- 701: TRAC_4_ Exogenou s_82 ATTATTAAGTAGCCCTGCATTTCAGGTTTCCTTGAGTGGCAGGCCAGGCCTGGCCGTGAAC GTTCACTGAAATCATGGCCTCTTGGCCAAGATTGATAGCTTGTGCCTGTCCCTGAGTCCCAG TCCATCACGAGCAGCTGG1 1 ILIAAGATGCTATTTCCCGTATAAAGCATGAGACCGTGACTT GCCAGCCCCACAGAGCCCCGCCCTTGTCCATCACTGGCATCTGGACTCCAGCCTGGGTTGG GGCAAAGAGGGAAATGAGATCATGTCCTAACCCTGATCCTCTTGTCCCACAGATATCCAGA ACCCTGACCCTGCCGTGTACCAGCTGAGAGACTCTAAATCCAGTGACAAGTCTGTCTGCCTA TTCACCGATTTTGATTCTCAAACAAATGTGTCACAAAGTAAGGATTCTGATGTGTATATCAC AGACAAAACTGTGCTAGACtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttc cttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtca ttctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgc ggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCC ACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTG GCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTGG GGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCC GCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTA CCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCC TGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGG CGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTC AACTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGC CTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGG GGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTC CGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCAC CGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGC TTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAG GCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGA GGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAA GGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTA TATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATC GAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGC CCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCA ACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGG CATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaattt cacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatATGAGGTCTATG GACTTCAAGAGCAACAGTGCTGTGGCCTGGAGCAACAAATCTGACTTTGCATGTGCAAACG CCTTCAACAACAGCATTATTCCAGAAGACACCTTCTTCCCCAGCCCAGGTAAGGGCAGCTTT GGTGCCTTCGCAGGCTGTTTCCTTGCTTCAGGAATGGCCAGGTTCTGCCCAGAGCTCTGGTC AATGATGTCTAAAACTCCTCTGATTGGTGGTCTCGGCCTTATCCATTGCCACCAAAACCCTCT TTTTACTAAGAAACAGTGAGCCTTGTTCTGGCAGTCCAGAGAATGACACGGGAAAAAAGCA GATGAAGAGAAGGTGGCAGGAGAGGGCACGTGGCCCAGCCTCAGTCTCTCCAACTGAGTT 2541 180 WO 2022/093846 PCT/US2021/056689 CCTG CCTG CCTG CCTTTG CTCAG ACTGTTTG CCCCTTACTG CTCTTCTAG G CCTCATTCTAAG C CCCTTpARBI- 702: TRAC_6_ Exogenou s_84 TTCATTTCCATTTGAGTTGTTCTTATTGAGTCATCCTTCCTGTGGTAGCGGAACTCACTAAGG GGCCCATCTGGACCCGAGGTATTGTGATGATAAATTCTGAGCACCTACCCCATCCCCAGAA GGGCTCAGAAATAAAATAAGAGCCAAGTCTAGTCGGTGTTTCCTGTCTTGAAACACAATAC TGTTGGCCCTGGAAGAATGCACAGAATCTGTTTGTAAGGGGATATGCACAGAAGCTGCAA GGGACAGGAGGTGCAGGAGCTGCAGGCCTCCCCCACCCAGCCTGCTCTGCCTTGGGGAAA ACCGTGGGTGTGTCCTGCAGGCCATGCAGGCCTGGGACATGCAAGCCCATAACCGCTGTG GCCTCTTGGTTTTACAGATACGAACCTAAACTTTCAAAACCTGTCAGTGATTGGGTTCCGAA TCCTCCTCCTGAAAGTGGCCGGGtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgt gccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtag gtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgg ggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACAT CGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGA AGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAG GGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 ICGCAACGGGT TTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCG CCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTG CCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGT CCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCT TGCTCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACC GGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTC ACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGC GTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGC ACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGC AGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCC GAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCG CCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACT TCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACG TCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAA CATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGA CGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGAC CCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTC TCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcaca aatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatTTTAATCTG CTCATGACGCTGCGGCTGTGGTCCAGCTGAGGTGAGGGGCCTTGAAGCTGGGAGTGGGGT TTAG G G ACG CG G GTCTCTG G GTG CATCCTAAG CTCTG AG AG CAAACCTCCCTG CAG G GTCT TGCTTTTAAGTCCAAAGCCTGAGCCCACCAAACTCTCCTACTTCTTCCTGTTACAAATTCCTCT TGTGCAATAATAATGGCCTGAAACGCTGTAAAATATCCTCATTTCAGCCGCCTCAGTTGCAC TTCTCCCCTATGAGGTAGGAAGAACAGTTGTTTAGAAACGAAGAAACTGAGGCCCCACAGC TAATGAGTGGAGGAAGAGAGACACTTGTGTACACCACATGCCTTGTGTTGTACTTCTCTCAC CGTGTAACCTCCTCATGTCCTCTCTCCCCAGTACGGCTCTCTTAGCTCAGTAGAAAGAAGAC ATTACACTC 2541 pARBI- 703: TRACExo genous_3 CAGTCCATCACGAGCAGCTGGTTTCTAAGATGCTATTTCCCGTATAAAGCATGAGACCGTGA CTTGCCAGCCCCACAGAGCCCCGCCCTTGTCCATCACTGGCATCTGGACTCCAGCCTGGGTT GGGGCAAAGAGGGAAATGAGATCATGTCCTAACCCTGATCCTCTTGTCCCACAGATATCCA GAACCCTGACCCTGCCGTGTACCAGCTGAGAGACTCTAAATCCAGTGACAAGTCTGTCTGC CTATTCACCGATTTTGATTCTCAAACAAATGTGTCACAAAGTAAGGATTCTGATGTGTATATC ACAGACAAAACTGTGCTAGACATGAGGTCTATGGACTTCAAGAGCAACAGTGCTGTGGCCT GGAGCAACAAATCTGACTTTGCATGTGCAAACGCCTTCAACAACAGCATTATTCCAGAAGA CACCTTCTTCCCCAGCCCAtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttcc ttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcatt ctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcg gtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCA CAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGGTGG 2541 181 WO 2022/093846 PCT/US2021/056689 CGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 1CCCGAGGGTGGG GGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 1CGCAACGGGTTTGCCG CCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCTACC TGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTCCTG AACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCGGCG CTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGCTCAA CTCTACGTCTTTGTTTCGTTTTCTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGCGCCT ACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGG TGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCG GCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG GCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTC AGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCT ACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGT GAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGA GGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATC ATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAG GACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC GTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACG AGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCAT GGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcaca aataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatGGTAAGGGCAGCTTT GGTGCCTTCGCAGGCTGTTTCCTTGCTTCAGGAATGGCCAGGTTCTGCCCAGAGCTCTGGTC AATGATGTCTAAAACTCCTCTGATTGGTGGTCTCGGCCTTATCCATTGCCACCAAAACCCTCT TTTTACTAAGAAACAGTGAGCCTTGTTCTGGCAGTCCAGAGAATGACACGGGAAAAAAGCA GATGAAGAGAAGGTGGCAGGAGAGGGCACGTGGCCCAGCCTCAGTCTCTCCAACTGAGTT CCTG CCTG CCTG CCTTTG CTCAG ACTGTTTG CCCCTTACTG CTCTTCTAG G CCTCATTCTAAG C CCCTTCTCCAAGTTGCCTCTCCTTAI 1 ILICCCTGTCTGCCAAAAAATCTTTCCCAGCTCACTA AGTCAGTCTCACGCAGTCACTCATTAACCCACCAATCACTGATTGTGCCGGCACATGAATGpARBI- 704: TRIM28_ l_Exogen ous_85 TGAGGAAGAAGCGCGGGCGGCGCCTTCGGGAGGCGAGCAGGCAGCAGTTGGCCGTGCCG TAGCAGCGTCCCGCGCGCGGCGGGCAGCGGCCCAGGAGGCGCGTGGCGGCGCTCGGCCT CGCGGCGGCGGCGGCGGCAGCGGCCCAGCAGTTGGCGGCGAGCGCGTCTGCGCCTGCGC GGCGGGCCCCGCGCCCCTCCTCCCCCCCTGGGCGCCCCCGGCGGCGTGTGAATGGCGGCCT CCGCGGCGGCAGCCTCGGCAGCAGCGGCCTCGGCCGCCTCTGGCAGCCCGGGCCCGGGCG AGGGCTCCGCTGGCGGCGAAAAGCGCTCCACCGCCCCTTCGGCCGCAGCCTCGGCCTCTGC CTCAGCCGCGGCGTCGTCGCCCGCGGGGGGCGGCGCCGAGGCGCTGGAGCTGCTGGAGC ACTGCGGCGTGTGCAGAGAGCGCCTGCGACCCtgacgactgtgccttctagttgccagccatctgttgttt gcccctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgc attgtctgagtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatag caggcatgctggggatgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAG AGCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGT GCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCTT TTTCCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCI 1 1 1 IC GCAACGGGTTTGCCGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACG CGCCCGCCGCCCTACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCG CCTGTGGTGCCTCCTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACC GGGCCTTTGTCCGGCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCC TGACCCTGCTTGCTCAACTCTACGTCTTTGTTTCGTIIICTGTTCTGCGCCGTTACAGATCCAA GCTGTGACCGGCGCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAG GAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCAC AAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAG TTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTA CGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCC GCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACA AGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGG GCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACA 2541 182 WO 2022/093846 PCT/US2021/056689 GCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGAT CCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCC ATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGA GCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCG GGATCACTCTCGGCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagc aatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatctta tGAGAGGGAGCCCCGCCTGCTGCCCTGTTTGCACTCGGCCTGTAGTGCCTGCTTAGGGCCC GCGGCCCCCGCCGCCGCCAACAGCTCGGGGGACGGCGGGGCGGCGGGCGACGGCACCGG TAAGTACGAAGTGATCGGTGCCACCCCTCCCCCTACTCTCTGCCTTTGATTCCGACTGGGTG CAGAGATGAGGATGCCACCTGGGCGAGAGGATGGGGGCCCGGACAGGGCACGGGAAATA Cl 1 ILIGGGTCCTGCATACGAACGTGGGTTTGTGCTGGCCGCTGAGATGGGACATCTGACT AAAGTTGGAGAAAAGAAGGCTCGGGGAGGGGAGGGGCTGGTTCGCTGCGGGATAATGGT CGGGGGCCCACCCAGCAGGGGAATGGTGGGGGCCATAACCTGGGTGGGAACTTGTAACA GTCTCCCACATCCCTGCTTCTCGAAGTGGTGpARBI- 705: TRIM28_ 2_Exogen ous_86 TCGAAGTGGTGGACTGTCCCGTGTGCAAGCAACAGTGCTTCTCCAAAGACATCGTGGAGAA TTATTTCATGCGTGATAGTGGCAGCAAGGCTGCCACCGACGCCCAGGATGCGAACCAGGTG CGTCCTATCTCAGCAACCACAAGGAGGI 1 ILIGGGGAGGGGGCATCTGCGCAGGAGGAGC TTGGCACCAGCTCCAGGCTGTTACTCCACTTTCCCAAGGCTCTGGGTGGGCTGCCTAGGTTG GGTCAAGGGACCAATCTTAAATCTCCGGTTGTATITICTGGGATGTAAACGTGGATCTATCA AGTTGTCTTGCCTTCTCTGACCCTGCCTTTGTCTGGCAGTGCTGCACTAGCTGTGAGGATAA TGCCCCAGCCACCAGCTACTGTGTGGAGTGCTCGGAGCCTCTGTGTGAGACCTGTGTAGAG GCGCACCAGCGGGTGAAGTACtgacgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgc cttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtg tcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgggga tgcggtgggctctatggGGATCTGCGATCGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACGGGTGCCTAGAGAAGG TGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCI 1 1 1 ICCCGAGGGTG GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTC1 1 1 1 1CGCAACGGGTTTGC CGCCAGAACACAGCTGAAGCTTCGAGGGGCTCGCATCTCTCCTTCACGCGCCCGCCGCCCT ACCTGAGGCCGCCATCCACGCCGGTTGAGTCGCGTTCTGCCGCCTCCCGCCTGTGGTGCCTC CTGAACTGCGTCCGCCGTCTAGGTAAGTTTAAAGCTCAGGTCGAGACCGGGCCTTTGTCCG GCGCTCCCTTGGAGCCTACCTAGACTCAGCCGGCTCTCCACGCTTTGCCTGACCCTGCTTGC TCAACTCTACGTCTTTGTTTCGTITICTGTTCTGCGCCGTTACAGATCCAAGCTGTGACCGGC GCCTACTCTAGAGCTAGCGAATTgccgccaccATGGTGAGCAAGGGCGAGGAGCTGTTCACC GGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTG TCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACC ACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGT GCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAA GGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCA AG G AG G ACG G CAACATCCTG G G G CACAAG CTG G AGTACAACTACAACAG CCACAACGTCT ATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACAT CGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG CCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCC AACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCG GCATGGACGAGCTGTACAAatgattgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatt tcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatACCAAGGACCA TACTGTGCGCTCTACTGGTACATGAGGCTGAGGGGGGCTGTTGGAGTTGTTCTCCCATGTG TGCCCTCAGTTGCTTTTATGATGTTGGTTGCATCTGGTGGATGGGTCCTAGAGTTCTCTAGG GGGTGCCGCCCGAAGGGCCCGAGGGCAGAACTCCAGAAGCAGAAAAACTGGGGTTGTGG TGTGTAGTCTCTAGGGCCTAGGTGGGAGAGGGTGGGAAGGGGAAATAAGGGAGACCTTA ATGTGCTGCAGGGAGGTACAAAGGGTTTGAGAAGGCTTATCAGGGAGTTGTCAGACCTGG TGGTGAAGGGCTCAGCATATGCAAACAGGGAAAGGCATGGTGTGAAGGGCTTTCTGGGTT TGTG GTTCCCTG G CACACATCTG GTATAAG ATG CTG CTAG G G A AAGTAG ACTGTG G GTCCA TGGATTATAAGTGATGA 2541 183

Claims (148)

1.WO 2022/093846 PCT/US2021/056689

2.CLAIMS 1. An engineered cell, comprising at least one sequence encoding a transgene, wherein the at least one sequence is inserted within a safe harbor locus, the safe harbor locus is at any one or more of an sgRNA target loci provided in Table 4; and wherein expression of the at least one sequence encoding the transgene is operatively linked to an endogenous promoter. 2. An engineered cell, comprising at least one sequence encoding a transgene, wherein the at least one sequence is inserted within a safe harbor locus, the safe harbor locus is at any one or more of an sgRNA target loci provided in Table 4; and wherein expression of the at least one sequence encoding the transgene is operatively linked to an exogenous promoter.

3. The engineered cell of claim 1 or 2, wherein the sgRNA target locus is selected from: chrl 1:128340000-128350000, chrl0:33130000-33140000, chrl0:72290000-72300000, chrl 1:65425000-65427000 (NEAT1), chrl5:92830000-92840000, chrl6:l 1220000- 11230000, chr2:87460000-87470000, chr3:186510000-186520000, chr3:59450000- 59460000, chr8:127980000-128000000, or chr9:7970000-7980000.

4. The engineered cell of any one of claims 1-3, wherein the sgRNA target locus is selected from: chrl 1:128340000-128350000, chrl0:72290000-72300000, chrl5:92830000- 92840000, or chrl6:11220000-11230000.

5. The engineered cell of any one of claims 1-4, wherein the sgRNA target locus is chrl 1:128340000-128350000.

6. The engineered cell of any one of claims 1-4, wherein the sgRNA target locus is chrl 5:92830000-92840000.

7. The engineered cell of claim 1 or 2, wherein the sgRNA target locus is a gene selected from: APRT, B2M, CAPNS1, CBLB, CD2, CD3E, CD3G, CDS, EDF1, FIL, PTEN, PTPN2, PTPN6, PTPRC, PTPRCAP, RPS23, RTRAF, SERF2, SLC38A1, SMAD2, SOCS1, SRP14, SRSF9, SUB1, TET2, TIGIT, TRAC, or TRIM28.

8. The engineered cell of any one of claims 1-3, wherein the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS94, GS88, GS89, GS90, GS91, GS92, GS93, GS95, GS96, GS97, GS98, GS99, GS100, GS101, GS102, GS103, GS104, GS105, GS106, GS107, GS108, GS109, GS110, GS111, GS112, GS113, GS114, GS115, GS116, GS117, GS118, GS119, or GS120.

9. The engineered cell of any one of claims 1-4, wherein the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS94, GS91, GS92, GS93, GS95, GS96, GS100, GS101, GS102, GS103, GS104, and GS105. 185 WO 2022/093846 PCT/US2021/056689

10. The engineered cell of claim 8 or 9, wherein the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS103, GS104, or GS105.

11. The engineered cell of claim 8 or 9, wherein the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS94, GS95, or GS96.

12. The engineered cell of claim 8 or 9, wherein the safe harbor locus is an GSintegration site in Table 4.

13. The engineered cell of claim 8 or 9, wherein the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS100, GS101, orGS102.

14. The engineered cell of claim 8 or 9, wherein the safe harbor locus is an GS1integration site in Table 4.

15. The engineered cell of claim 8 or 9, wherein the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS91, GS92, or GS93.

16. The engineered cell of any one of claims 2-15, wherein the exogenous promoter is an EFla promoter.

17. The engineered cell of any one of claims 1-16, wherein the engineered cell is a stem cell, a human cell, a primary cell, an hematopoietic cell, an adaptive immune cell, an innate immune cell, a T cell or a T cell progenitor.

18. The engineered cell of claim 17, wherein the cell is a T cell or a T cell progenitor.

19. The engineered cell of any one of claims 1-18, wherein the engineered cell isundifferentiated.

20. The engineered cell of any one of claims 1-18, wherein the engineered cell is CD45RA* and CCR7+.

21. The engineered cell of any one of claims 1-20, wherein the transgene encodes a recombinant protein, optionally a therapeutic agent.

22. The engineered cell of any one of claims 1-21, wherein the transgene encodes a chimeric antigen receptor (CAR).

23. A composition comprising the engineered cell of any one of claims 1-22 and a pharmaceutical excipient.

24. A guide ribonucleic acids (gRNA) for editing a cell at a safe harbor locus, wherein gRNA comprises any one of the sgRNA sequences in Table 4.

25. The gRNA of claim 24, wherein the gRNA comprises any one of SEQ ID NOS: 1-120.

26. The gRNA of claim 24 or 25, wherein the gRNA comprises any one of SEQ ID NOS:91-96 and 100-105.186 WO 2022/093846 PCT/US2021/056689

27. The gRNA of any one of claims 24-26, wherein the gRNA comprises SEQID NO:94or SEQ ID NO:102.

28. The gRNA of any one of claims 24-26, wherein the gRNA comprises SEQ ID NO:94.

29. The gRNA of any one of claims 24-26, wherein the gRNA comprises SEQ IDNO: 102.

30. The gRNA of any one of claims 24-29, wherein the cell is a stem cell, a human cell, a primary cell, an hematopoietic cell, an adaptive immune cell, an innate immune cell, a T cell or a T cell progenitor.

31. A method of editing a cell having chromosomal DNA, comprising inserting at least one sequence encoding a transgene within a safe harbor locus in the chromosomal DNA of the cell, wherein the safe harbor locus is any one or more of the sgRNA target loci provided in Table 4.

32. The method of claim 31, wherein the sgRNA target locus is selected from: chrl 1:128340000-128350000, chrl0:33130000-33140000, chrl0:72290000-72300000, chrl 1:65425000-65427000 (NEAT1), chrl5:92830000-92840000, chrl6:l 1220000- 11230000, chr2:87460000-87470000, chr3:186510000-186520000, chr3:59450000- 59460000, chr8:127980000-128000000, or chr9:7970000-7980000.

33. The method of claim 31 or 32, wherein the sgRNA target locus is selected from: chrl 1:128340000-128350000, chrl0:72290000-72300000, chrl5:92830000-92840000, or chrl6:11220000-11230000.

34. The method of any one of claims 31-33, wherein the sgRNA target locus is chrl 1:128340000-128350000.

35. The method of any one of claims 31-33, wherein the sgRNA target locus is chrl 5:92830000-92840000.

36. The method of claim 31, wherein the sgRNA target locus is a gene selected from: APRT, B2M, CAPNS1, CBLB, CD2, CD3E, CD3G, CDS, EDF1, FIL, PTEN, PTPN2, PTPN6, PTPRC, PTPRCAP, RPS23, RTRAF, SERF2, SLC38A1, SMAD2, SOCS1, SRP14, SRSF9, SUB1, TET2, TIGIT, TRAC, or TRIM28.

37. The method of claim 31 or 32, wherein the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS94, GS88, GS89, GS90, GS91, GS92, GS93, GS95, GS96, GS97, GS98, GS99, GS100, GS101, GS102, GS103, GS104, GS105, GS106, GS107, GS108, GS109, GS110, GS111, GS112, GS113, GS114, GS115, GS116, GS117, GS118, GS119, or GS120.187 WO 2022/093846 PCT/US2021/056689

38. The method of any one of claims 31-33, wherein the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS94, GS91, GS92, GS93, GS95, GS96, GS100, GS101, GS102, GS103, GS104, or GS105.

39. The method of any one of claims 31-33, wherein the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS103, GS104, or GS105.

40. The method of any one of claims 31-33, wherein the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS94, GS95, or GS96.

41. The method of any one of claims 31-33, wherein the safe harbor locus is the GSintegration site in Table 4.

42. The method of any one of claims 31-33, wherein the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS100, GS101, or GS102.

43. The method of any one of claims 31-33, wherein the safe harbor locus is the GS1integration site in Table 4.

44. The method of any one of claims 31-33, wherein the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS91, GS92, or GS93.

45. The method of any one of claims 31-44, wherein the transgene encodes a recombinant protein, optionally a therapeutic agent.

46. The method of any one of claims 31-45, wherein the transgene encodes a chimeric antigen receptor (CAR).

47. The method of any one of claims 31-46, wherein the at least one sequence comprises an exogenous promoter and the exogenous promoter is operably linked to the transgene.

48. The method of claim 47, wherein the exogenous promoter is an EFla promoter.

49. The method of any one of claims 31-48, wherein the cell is a stem cell, a human cell,a primary cell, an hematopoietic cell, an adaptive immune cell, an innate immune cell, a T cell or T cell progenitor.

50. The method of claim 49, wherein the cell is a T cell or a T cell progenitor.

51. The method of any one of claims 31-50, wherein the engineered cell is undifferentiated.

52. The method of any one of claims 31-51, wherein the engineered cell is CD45RA+ and CCR7+.

53. The method of any one of claims 31-52, wherein the at least one sequence is inserted using a homology-directed repair. 188 WO 2022/093846 PCT/US2021/056689

54. The method of any one of claims 31-52, wherein the at least one sequence is insertedusing a homology independent targeted insertion.

55. The method of any one of claims 31-54, wherein the at least one sequence is insertedusing one or more guide ribonucleic acids (gRNAs) and one or more Cas9 endonucleases.

56. The method of claim 55, wherein the one or more gRNAs comprises any one of SEQ ID NOS: 1-120.

57. The method of claim 55 or 56, wherein the one or more gRNAs comprises any one ofSEQ ID NOS: 91-96 and 100-105.

58. The method of any one of claims 55-57, wherein the gRNA comprises SEQ ID NO:94or SEQ ID NO: 102.

59. The method of any one of claims 55-58, wherein the gRNA comprises SEQ IDNO:94.

60. The method of any one of claims 55-58, wherein the gRNA comprises SEQ IDNO: 102.

61. A method of editing a T cell, comprising contacting a T cell with one or more guide ribonucleic acids (gRNAs), at least one sequence encoding a transgene, and one or more Casendonucleases, wherein the one or more gRNAs and Cas9 endonucleases facilitate the insertion of the at least one sequence into chromosomal DNA within a safe harbor locus, wherein the safe harbor locus is selected from any one or more of an sgRNA target loci in Table 4.

62. The method of claim 61, wherein the one or more gRNAs comprises a sequenceselected from any one of the sgRNA sequences in Table 4.

63. The method of claim 61 or 62, wherein the one or more gRNAs comprises any one ofSEQ ID NOS: 1-120.

64. The method of any one of claims 61-63, wherein the one or more gRNAs comprisesany one of SEQ ID NOS: 91-96 and 100-105.

65. The method of any one of claims 61-64, wherein the gRNA comprises SEQ ID NO:94or SEQ ID NO: 102.

66. The method of any one of claims 61-65, wherein the gRNA comprises SEQ IDNO:94.

67. The method of any one of claims 61-65, wherein the gRNA comprises SEQ ID NO: 102. 189 WO 2022/093846 PCT/US2021/056689

68. The method of any one of claims 61-67, wherein the sgRNA target locus is selectedfrom: chrl 1:128340000-128350000, chrl0:33130000-33140000, chrl0:72290000-72300000, chrl 1:65425000-65427000 (NEAT1), chrl5:92830000-92840000, chrl6:l 1220000- 11230000, chr2:87460000-87470000, chr3:186510000-186520000, chr3:59450000- 59460000, chr8:127980000-128000000, or chr9:7970000-7980000.

69. The method of any one of claims 61-68, wherein the sgRNA target locus is selectedfrom: chrl 1:128340000-128350000, chrl0:72290000-72300000, chrl5:92830000-92840000, or chrl6:11220000-11230000.

70. The method of any one of claims 61-69, wherein the sgRNA target locus ischrl 1:128340000-128350000.

71. The method of any one of claims 61-69, wherein the sgRNA target locus ischrl 5:92830000-92840000.

72. The method of claim 61-67, wherein the sgRNA target locus is a gene selected from:APRT, B2M, CAPNS1, CBLB, CD2, CD3E, CD3G, CDS, EDF1, FIL, PTEN, PTPN2, PTPN6, PTPRC, PTPRCAP, RPS23, RTRAF, SERF2, SLC38A1, SMAD2, SOCS1, SRP14, SRSF9, SUB1, TET2, TIGIT, TRAC, or TRIM28.

73. The method of any one of claims 61-68, wherein the safe harbor locus is selectedfrom any one of the integration sites in Table 4 designated: GS94, GS88, GS89, GS90, GS91, GS92, GS93, GS95, GS96, GS97, GS98, GS99, GS100, GS101, GS102, GS103, GS104, GS105, GS106, GS107, GS108, GS109, GS110, GS111, GS112, GS113, GS114, GS115, GS116, GS117, GS118, GS119, or GS120.

74. The method of any one of claims 61-68 and 73, wherein the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS94, GS91, GS92, GS93, GS95, GS96, GS100, GS101, GS102, GS103, GS104, or GS105.

75. The method of any one of claims 61-68 and 73-74, wherein the safe harbor locus isselected from any one of the integration sites in Table 4 designated: GS103, GS104, or GS105.

76. The method of any one of claims 61-68 and 73-74, wherein the safe harbor locus isselected from any one of the integration sites in Table 4 designated: GS94, GS95, and GS96.

77. The method of claim 76, wherein the safe harbor locus is the GS94 integration site inTable 4. 190 WO 2022/093846 PCT/US2021/056689

78. The method of any one of claims 61-68 and 73-74, wherein the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS100, GS101, or GS102.

79. The method of claim 78, wherein the safe harbor locus is the GS102 integration site in Table 4.

80. The method of any one of claims 61-68 and 73-74, wherein the safe harbor locus is selected from any one of the integration sites in Table 4 designated: GS91, GS92, or GS93.

81. The method of any one of claims 61-80, wherein the engineered cell is undifferentiated.

82. The method of any one of claims 61-81, wherein the engineered cell is CD45RA+ and CCR7+.

83. An ex vivo method of obtaining an engineered cell or population thereof, comprising:a. obtaining a cell; b. genetically modifying the cell by inserting at least one sequence encoding a transgene within a safe harbor locus, wherein the safe harbor locus is selected from any one of an sgRNA target loci in Table 4.

84. The method of claim 83, wherein obtaining the cell comprises: (i) collecting a tissue sample from a subject, (ii) isolating the cells from the tissue samples, and (iii) culturing the cells in vitro.

85. The method of claim 84, wherein the tissue sample is a blood sample.

86. The method of any one of claims 83-85, wherein the cell is a stem cell, a human cell,a primary cell, an hematopoietic cell, an adaptive immune cell, an innate immune cell, a T cell, or T cell progenitor.

87. The method of claim 86, wherein the cell is a T cell or a T cell progenitor.

88. The method of any one of claims 83-87, wherein the engineered cell is undifferentiated.

89. The method of any one of claims 83-88, wherein the engineered cell is CD45RA+ and CCR7+.

90. The method of any one of claims 83-89, wherein the at least one sequence is inserted using a homology-directed repair.

91. The method of any one of claims 83-89, wherein the at least one sequence is inserted using a homology independent targeted insertion. 191 WO 2022/093846 PCT/US2021/056689

92. The method of any one of claims 83-91, wherein the genetically modifying in step (b) comprises contacting the cell with one or more guide ribonucleic acids (gRNAs), the at least one sequence, and one or more Cas9 endonucleases, wherein the one or more gRNAs and Cas9 endonucleases facilitate the insertion of the at least one sequence into chromosomal DNA within the safe harbor locus.

93. The method of claim 92, wherein the one or more gRNAs comprises a sequence selected from any one of the sgRNA sequences in Table 4.

94. The method of any one of claims 83-93, wherein the transgene encodes a recombinant protein, optionally a therapeutic agent.

95. The method of any one of claims 83-93, wherein the transgene encodes a chimeric antigen receptor (CAR).

96. The method of claim 83-95, wherein the at least one sequence comprises an exogenous promoter and the exogenous promoter is operably linked to the transgene.

97. The method of claim 96, wherein the exogenous promoter is an EFla promoter.

98. A method of treating a subject having or at risk of having a disease, comprising administering to the subject an effective amount of the cell of any one of claims 1-22, a population thereof, or the composition of claim 23.

99. The method of claim 98, wherein the cell, the population thereof, or the composition is administered to the subject by infusion.

100. A method of treating a subject having or at risk of having a disease, comprising:a. conducting the method of any one of claims 83-97; and b. administering to the subject an effective amount of a composition comprising the cell or a population thereof.

101. The method of claim 100, wherein the composition is administered to the subject by infusion.

102. The method of claim 100 or 101, wherein the disease is cancer.

103. The method of any one of claims 100-102 or , wherein the disease is blood cancer.

104. A method of identifying a safe harbor locus, comprising:a. identifying genes or non-coding regions in a chromosome that are above a threshold level for expression across developmental cell states and/or a threshold level for accessibility of chromatin; 192 WO 2022/093846 PCT/US2021/056689 b. generating a linear model that correlates the gene or non-coding region from step (a) with knock-in (KI) efficiency and estimates the KI efficiency of any gene or coding region on the chromosome; and c. selecting the safe harbor locus based on threshold parameters; wherein the safe harbor locus is selected for insertion of at least one sequence encoding a transgene within a cell.

105. The method of claim 104, wherein the threshold parameters include one or more of: stable expression of a transgene, knockout of the gene confers benefit to the function of the cell, no known function within the cell, stable transgene expression in vitro with or without CD3/CD28 stimulation, negligible off-target cleavage as detected by iGuide-Seq or CRISPR- Seq, less off-target cleavage relative to other loci as detected by iGuide-Seq or CRISPR-Seq, negligible transgene-independent cytotoxicity, negligible transgene-independent cytokine expression, negligible transgene-independent chimeric antigen receptor expression, negligible deregulation or silencing of nearby genes, and positioned outside of a cancer-related gene.

106. The method of claim 105, wherein the stable expression of a transgene at the safe harbor locus is less than or equal to 2-fold expression change over the course of at least 1, 2, 3, 4, 5, 6, or 7 days, and wherein expression change is measured by mean fluorescence intensity of a reporter gene encoded by the at least one sequence.

107. The method of any one of claims 104-106, wherein the accessibility of chromatin is measured using an assay for transposase-accessible chromatin using sequencing (ATAC-seq).

108.The method of any one of claims 104-107, wherein the level of expression across developmental cell states is measured using RNA sequencing (RNA-seq).

109. The method of any one of claims 104-108, wherein the cell is a stem cell, a human cell, a primary cell, an hematopoietic cell, an adaptive immune cell, an innate immune cell, a T cell or T cell progenitor.

110. The method of any one of claims 104-109, wherein the linear model has a coefficient of determination (R2 value) of at least 30%.

111. The engineered cell, composition, gRNA or method of any one of the preceding claims, wherein insertion within the safe harbor locus increase cell cytotoxicity of diseased cells. 193 WO 2022/093846 PCT/US2021/056689

112. The engineered cell, composition, gRNA or method of any one of the preceding claims wherein knock-in efficiency at the safe harbor locus is increased relative to other locations along the chromosome.

113. An engineered cell, comprising at least one sequence encoding a transgene, wherein the at least one sequence is inserted within a safe harbor locus, wherein the safe harbor locus is at any one or more of an sgRNA target loci; and wherein expression of the at least one sequence encoding the transgene is operatively linked to an endogenous promoter or an exogenous promoter, and wherein the engineered cell is undifferentiated.

114. The engineered cell of claim 113, wherein the safe harbor locus is selected any one of the integration sites designated: GS94, GS88, GS89, GS90, GS91, GS92, GS93, GS95, GS96, GS97, GS98, GS99, GS100, GS101, GS102, GS103, GS104, GS105, GS106, GS107, GS108, GS109, GS110, GS111, GS112, GS113, GS114, GS115, GS116, GS117, GS118, GS119, or GS120.

115. The engineered cell of claim 113 or 114, wherein the safe harbor locus is the GSintegration site.

116. The engineered cell of claim 113, wherein the sgRNA target locus is selected from: chrl 1:128340000-128350000, chrl0:33130000-33140000, chrl0:72290000-72300000, chrl 1:65425000-65427000 (NEAT1), chrl5:92830000-92840000, chrl6:l 1220000- 11230000, chr2:87460000-87470000, chr3:186510000-186520000, chr3:59450000- 59460000, chr8:127980000-128000000, or chr9:7970000-7980000.

117. The engineered cell of claim 113, wherein the sgRNA target locus is a gene selected from: APRT, B2M, CAPNS1, CBLB, CD2, CD3E, CD3G, CDS, EDF1, FIL, PTEN, PTPN2, PTPN6, PTPRC, PTPRCAP, RPS23, RTRAF, SERF2, SLC38A1, SMAD2, SOCS1, SRP14, SRSF9, SUB1, TET2, TIGIT, TRAC, or TRIM28.

118. The engineered cell of any one of claims 113-117, wherein the one or more gRNAs comprises any one of SEQ ID NOS: 1-120.

119. The engineered cell of any one of claims 113-118, wherein the engineered cell is a stem cell, a human cell, a primary cell, an hematopoietic cell, an adaptive immune cell, an innate immune cell, a T cell or a T cell progenitor.

120. The engineered cell of claim 119, wherein the cell is a T cell or a T cell T cell progenitor.

121. The engineered cell of any one of claims 113-120, wherein the engineered cell is CD45RA+ and CCR7+. 194 WO 2022/093846 PCT/US2021/056689

122. The engineered cell of any one of claims 113-121, wherein the transgene encodes a recombinant protein, optionally a therapeutic agent.

123. The engineered cell of any one of claims 113-122, wherein the transgene encodes a chimeric antigen receptor (CAR).

124. A composition comprising the engineered cell of any one of claims 113-123 and a pharmaceutical excipient.

125. A method of editing a cell having chromosomal DNA, comprising inserting at least one sequence encoding a transgene within a safe harbor locus in the chromosomal DNA of the cell, wherein the safe harbor locus is at any one or more of an sgRNA target loci; and wherein the engineered cell is undifferentiated.

126. The method of claim 125, wherein the engineered cell is a stem cell, a human cell, a primary cell, an hematopoietic cell, an adaptive immune cell, an innate immune cell, a T cell or a T cell progenitor.

127. The method of claim 125 or 126, wherein the cell is a T cell or a T cell progenitor.

128. A method of editing a T cell, comprising contacting a T cell with one or more guideribonucleic acids (gRNAs), at least one sequence encoding a transgene, and one or more Casendonucleases, wherein the one or more gRNAs and Cas9 endonucleases facilitate the insertion of the at least one sequence into chromosomal DNA within a safe harbor locus.

129. The method of any one of claims 125-128, wherein the safe harbor locus is selected from any one of the integration sites designated: GS88, GS89, GS90, GS91, GS92, GS93, GS94, GS95, GS96, GS97, GS98, GS99, GS100, GS101, GS102, GS103, GS104, GS105, GS106, GS107, GS108, GS109, GS110, GS111, GS112, GS113, GS114, GS115, GS116, GS117, GS118, GS119, or GS120.

130. The method of any one of claims 125-128, wherein the safe harbor locus is the GSintegration site.

131. The method of any one of claims 125-128, wherein the sgRNA target locus is selected from: chrl 1:128340000-128350000, chrl0:33130000-33140000, chrl0:72290000-72300000, chrl 1:65425000-65427000 (NEAT1), chrl5:92830000-92840000, chrl6:l 1220000- 11230000, chr2:87460000-87470000, chr3:186510000-186520000, chr3:59450000- 59460000, chr8:127980000-128000000, or chr9:7970000-7980000.

132. The method of any one of claims 125-128, wherein the sgRNA target locus is a gene selected from: APPT, B2M, CAPNS1, CBLB, CD2, CD3E, CD3G, CDS, EDF1, FIL, PTEN, 195 WO 2022/093846 PCT/US2021/056689 PTPN2, PTPN6, PTPRC, PTPRCAP, RPS23, RTRAF, SERF2, SLC38A1, SMAD2, S0CS1, SRP14, SRSF9, SUB1, TET2, TIGIT, TRAC, or TRIM28.

133. The method of any one of claims 125-132, wherein the one or more gRNAs comprises any one of SEQ ID NOS: 1-120.

134. The method of any one of claims 125-133, wherein the engineered cell is CD45RA+ and CCR7+ after insertion of the at least one sequence into the safe harbor locus.

135. The method of any one of claims 125-134, wherein the transgene encodes a recombinant protein, optionally a therapeutic agent.

136. The method of any one of claims 125-135, wherein the transgene encodes a chimeric antigen receptor (CAR).

137. An ex vivo method of obtaining an undifferentiated engineered cell or population thereof, comprising:c. obtaining a cell; d. genetically modifying the cell by inserting at least one sequence encoding a transgene within a safe harbor locus, wherein the engineered cell is undifferentiated.

138. The method of claim 137, wherein obtaining the cell comprises: (i) collecting a tissue sample from a subject, (ii) isolating the cells from the tissue samples, and (iii) culturing the cells in vitro.

139. The method of claim 138, wherein the tissue sample is a blood sample.

140. The method of any one of claims 137-139, wherein the cell is a stem cell, a human cell, a primary cell, an hematopoietic cell, an adaptive immune cell, an innate immune cell, a T cell or T cell progenitor.

141. The method of claim 140, wherein the cell is a T cell or a T cell progenitor.

142. The method of any one of claims 137-142, wherein the engineered cell is CD45RA+ and CCR7+.

143. The method of any one of claims 137-143, wherein the transgene encodes a recombinant protein, optionally a therapeutic agent.

144. The method of any one of claims 137-143, wherein the transgene encodes a chimeric antigen receptor (CAR). 196 WO 2022/093846 PCT/US2021/056689

145. A method of treating a subject having or at risk of having a disease, comprising administering to the subject an effective amount of the cell of any one of claims 113-123, a population thereof, or the composition of claim 124.

146. A method of treating a subject having or at risk of having a disease, comprising: c. conducting the method of any one of claims 125-144; and d. administering to the subject an effective amount of a composition comprising the cell or a population thereof.

147. The method of claim 146, wherein the composition is administered to the subject by infusion.

148. The method of claim 146 or 147, wherein the disease is cancer. 197