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Nyberg WA, Wang CH, Ark J, Liu C, Clouden S, Qualls A, Caryotakis S, Wells E, Simon K, Garza C, Bernard PL, Lopez-Ichikawa M, Li Z, Seo J, Kimmerly GR, Muldoon JJ, Chen PA, Li M, Liang HE, Kersten K, Rosales A, Kuhn N, Ye CJ, Gardner JM, Molofsky A, Ricardo-Gonzalez RR, Asokan A, Eyquem J
Immunity 58 (2) 499-512.e7 [2025-02-11; online 2025-02-04]
Genetic engineering of T cells in mouse models is essential for investigating immune mechanisms. We aimed to develop an approach to manipulate T cells in vivo using an evolved adeno-associated virus (AAV) capsid named Ark313. Delivery of a transient transgene expression cassette was feasible using Ark313, and this serotype outperformed natural serotypes. A single intravenous injection of a Cre recombinase-expressing Ark313 in the Ai9 fluorescent reporter mouse model achieved permanent genetic modifications of T cells. Ark313 facilitated in vivo gene editing in both tissue-resident and splenic T cells and validation of immunotherapy targets in solid tumor models. Ark313 delivered large DNA donor templates to T cells in vivo and integrated transgenes in primary CD4+ and CD8+ T cells, including naive T cells. Ark313-mediated transgene delivery presents an efficient approach to target mouse T cells in vivo and a resource for the interrogation of T cell biology and for immunotherapy applications.
PubMed 39909036
DOI 10.1016/j.immuni.2025.01.009
Crossref 10.1016/j.immuni.2025.01.009
pii: S1074-7613(25)00034-2