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An evolved AAV variant enables efficient genetic engineering of murine T cells.
Nyberg, William A; Ark, Jonathan; To, Angela; Clouden, Sylvanie; Reeder, Gabriella; Muldoon, Joseph J; Chung, Jing-Yi; Xie, William H; Allain, Vincent; Steinhart, Zachary; Chang, Christopher; Talbot, Alexis; Kim, Sandy; Rosales, Alan; Havlik, L Patrick; Pimentel, Harold; Asokan, Aravind; Eyquem, Justin.
Afiliação
  • Nyberg WA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
  • Ark J; Department of Molecular Genetics & Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.
  • To A; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
  • Clouden S; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
  • Reeder G; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94131, USA.
  • Muldoon JJ; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
  • Chung JY; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
  • Xie WH; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94131, USA.
  • Allain V; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Université de Paris Cité, INSERM UMR976, Hôpital St-Louis, Paris, France.
  • Steinhart Z; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
  • Chang C; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94131, USA; Medical Scientist
  • Talbot A; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Université de Paris Cité, INSERM UMR976, Hôpital St-Louis, Paris, France.
  • Kim S; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Rosales A; Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA.
  • Havlik LP; Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA.
  • Pimentel H; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, Sloan Foundation, Departments of Computational Medicine, Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Asokan A; Department of Molecular Genetics & Microbiology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA. Electronic address: aravind.
  • Eyquem J; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University
Cell ; 186(2): 446-460.e19, 2023 01 19.
Article em En | MEDLINE | ID: mdl-36638795
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T / Engenharia Genética / Dependovirus Idioma: En Ano de publicação: 2023 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T / Engenharia Genética / Dependovirus Idioma: En Ano de publicação: 2023 Tipo de documento: Article