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However, current CAR-T cell therapy requires ex vivo T cell engineering, which is both time-consuming and cost-prohibitive, adding complexity to the overall treatment. In this study, using an engineered Sindbis virus envelope, we developed a lentiviral vector system with high specificity for targeting human T cell line and primary T cells, but not targeting other immune cell subsets. Notably, this T cell-specific lentiviral vector does not require additional anti-CD3\/CD28 stimulation for primary T cell activation during infection in vitro. Furthermore, the lentiviral vector successfully delivered a CD19-targeting CAR molecule to human primary T cells in vivo. The in vivo generated CD19-CAR-T cells efficiently mediated B cell lymphoma clearance. Overall, our study provides a promising tool for the development of in vivo T cell engineering approaches.<\/jats:p>","DOI":"10.1038\/s41598-025-17342-1","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T09:19:09Z","timestamp":1773739149000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A targeting lentiviral vector for generation of CAR-T cells in vivo"],"prefix":"10.1038","volume":"16","author":[{"given":"Muhadasi","family":"Tuerxunyiming","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo Michael","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoxuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"17342_CR1","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/s41571-023-00754-1","volume":"20","author":"KM Cappell","year":"2023","unstructured":"Cappell, K. 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