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However, its broader clinical translation is constrained by complex and costly ex vivo manufacturing, variable product quality, and limited control over in vivo activity. In vivo CAR\u2010T engineering enables direct T\u2010cell programming in the body, reducing reliance on ex vivo manufacturing while improving T\u2010cell fitness and antitumor efficacy. This approach also enables flexible dosing and may obviate lymphodepletion. This review first summarizes recent advances in in vivo CAR\u2010T engineering and the evolution of CAR architectures. We then examine viral and non\u2010viral delivery systems, including lentiviral vectors (LVs), adeno\u2010associated virus (AAV) vectors, lipid nanoparticles (LNPs), polymeric nanoparticles (PNPs), and emerging platforms, highlighting their distinct advantages and limitations. We further evaluate strategies to facilitate clinical translation, focusing on safety and efficacy. 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This review provides a framework for understanding in vivo CAR\u2010T engineering and highlights key strategies for overcoming translational barriers and advancing next\u2010generation CAR\u2010T therapies.<\/jats:p>","DOI":"10.1002\/mco2.71030","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:30:57Z","timestamp":1790515857000},"source":"Crossref","is-referenced-by-count":0,"title":["Advancing In Vivo Chimeric Antigen Receptor T\u2010Cell Engineering to Accelerate Clinical Translation"],"prefix":"10.1002","volume":"7","author":[{"given":"Zhenxin","family":"Bai","sequence":"first","affiliation":[{"name":"Department of General Surgery The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital)  Suzhou China"},{"name":"Department of Breast Surgery First Affiliated Hospital School of Medicine Zhejiang University  Hangzhou 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