{"doi":"10.1016/j.cell.2022.12.022","title":"An evolved AAV variant enables efficient genetic engineering of murine T cells","abstract":"Precise targeting of large transgenes to T cells using homology-directed repair has been transformative for adoptive cell therapies and T cell biology. Delivery of DNA templates via adeno-associated virus (AAV) has greatly improved knockin efficiencies, but the tropism of current AAV serotypes restricts their use to human T cells employed in immunodeficient mouse models. To enable targeted knockins in murine T cells, we evolved Ark313, a synthetic AAV that exhibits high transduction efficiency in murine T cells. We performed a genome-wide knockout screen and identified QA2 as an essential factor for Ark313 infection. We demonstrate that Ark313 can be used for nucleofection-free DNA delivery, CRISPR-Cas9-mediated knockouts, and targeted integration of large transgenes. Ark313 enables preclinical modeling of Trac-targeted CAR-T and transgenic TCR-T cells in immunocompetent models. Efficient gene targeting in murine T cells holds great potential for improved cell therapies and opens avenues in experimental T cell immunology.","journal":"Cell","year":2023,"id":316606,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":97,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9464,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":500720,"name":"Jonathan Ark","orcid":"0000-0003-4991-1422","position":1,"is_corresponding":false},{"id":627560,"name":"Angela To","orcid":"0000-0002-4622-0039","position":2,"is_corresponding":false},{"id":1020755,"name":"Sylvanie Clouden","orcid":null,"position":3,"is_corresponding":false},{"id":553727,"name":"Gabriella C. Reeder","orcid":"0000-0001-7286-4615","position":4,"is_corresponding":false},{"id":287698,"name":"Joseph J. Muldoon","orcid":"0000-0003-3784-3565","position":5,"is_corresponding":false},{"id":251790,"name":"Jing-Yi Chung","orcid":"0000-0001-5801-2416","position":6,"is_corresponding":false},{"id":1020306,"name":"William Xie","orcid":"0000-0002-0376-7165","position":7,"is_corresponding":false},{"id":1018207,"name":"Vincent Allain","orcid":"0000-0002-1068-7892","position":8,"is_corresponding":false},{"id":233584,"name":"Zachary Steinhart","orcid":"0000-0002-7344-5700","position":9,"is_corresponding":false},{"id":1016247,"name":"Christopher Chang","orcid":"0000-0003-3124-8773","position":10,"is_corresponding":false},{"id":805861,"name":"Alexis Talbot","orcid":"0000-0001-6734-413X","position":11,"is_corresponding":false},{"id":769816,"name":"Sandy Kim","orcid":null,"position":12,"is_corresponding":false},{"id":1020307,"name":"Alan Rosales","orcid":"0000-0001-6986-2985","position":13,"is_corresponding":false},{"id":346635,"name":"L. Patrick Havlik","orcid":null,"position":14,"is_corresponding":false},{"id":78901,"name":"Harold Pimentel","orcid":"0000-0001-8556-2499","position":15,"is_corresponding":false},{"id":265976,"name":"Aravind Asokan","orcid":"0000-0001-5563-4877","position":16,"is_corresponding":false},{"id":805865,"name":"Justin Eyquem","orcid":"0000-0001-8262-1190","position":17,"is_corresponding":false},{"id":842013,"name":"William A. Nyberg","orcid":"0000-0002-9982-1305","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T01:06:38.213358Z","pmid":"36638795","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}