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To overcome this barrier, we have developed a CD7-targeted rAAV vector (CD7-AAV6\/9) featuring a nanobody-fused hybrid capsid derived from a rationally selected chimeric combination of AAV6 and AAV9. CD7-AAV6\/9 enables efficient and selective transduction of immortalized and primary human T and NK cells\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                    in a humanized mouse model, achieves high production titers, and exhibits markedly reduced off-target transduction compared with wild-type serotypes. Incorporation of a human gene\u2013derived intron into the vector genome to overcome host-mediated transcriptional repression enables robust transgene expression in human CD7\n                    <jats:sup>+<\/jats:sup>\n                    T lymphocyte and NK cell populations. Together, our findings establish an integrated capsid\u2013genome design framework for targeting human T and NK cells, notoriously challenging immune cell populations for gene therapy, and provide a versatile platform readily adaptable to alternative surface markers and therapeutic payloads.\n                  <\/jats:p>","DOI":"10.1177\/10430342261487919","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:29:02Z","timestamp":1789619342000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of a Recombinant Adeno-Associated Virus Vector for Human T Lymphocyte- and Natural Killer Cell-Targeted Gene Therapy"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2975-6893","authenticated-orcid":false,"given":"Hendrik","family":"Jahnz","sequence":"first","affiliation":[{"name":"Leibniz Institute of Virology (LIV), Hamburg, 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