| First Author | Nyberg WA | Year | 2023 |
| Journal | Cell | Volume | 186 |
| Issue | 2 | Pages | 446-460.e19 |
| PubMed ID | 36638795 | Mgi Jnum | J:332907 |
| Mgi Id | MGI:7430605 | Doi | 10.1016/j.cell.2022.12.022 |
| Citation | Nyberg WA, et al. (2023) An evolved AAV variant enables efficient genetic engineering of murine T cells. Cell 186(2):446-460.e19 |
| abstractText | 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. |
