Agent Capital’s Associate, Jonathan Ark’s PhD Work Published in Cell

January 12, 2023


Agent Capital’s Associate, Jonathan Ark’s PhD work, in the laboratory of Aavind Asokan, PhD, was published in Cell. The article entitled “An evolved AAV variant enables efficient genetic engineering of murine T cells” discovered a novel murine T cell-specific AAV variant and explored its immunotherapeutic utility in immune competent hosts.



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 demon- strate 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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