{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:46:51Z","timestamp":1785847611263,"version":"3.56.0"},"reference-count":125,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Ex vivo CAR-T changed cancer care, but its made-to-order manufacturing keeps too many patients waiting.\n                    <jats:italic>In vivo<\/jats:italic>\n                    CAR-T takes a different path: deliver the genetic blueprint to a patient\u2019s own immune cells and let the body build the therapy. In this review, we compare the leading delivery platforms\u2014retargeted lentiviral vectors, engineered AAVs, LNPs (mRNA\/circRNA), polymeric nanoparticles, and bioinspired systems\u2014through the lenses of specificity, expression durability, redosing, manufacturability, immunogenicity, safety, and clinical maturity. Early human observations in hematologic malignancies and autoimmune disease show what\u2019s possible; solid-tumor progress is still largely preclinical. Key translational challenges include: off-target transduction and murky biodistribution, liver-skewed exposure for non-viral systems, integration risk for durable vectors, repeat-dose immunity, CMC consistency, and regulatory fit. We outline a practical roadmap\u2014quantitative biodistribution and potency, cargo-tuned persistence, receptor-aware targeting, robust CMC, and indication-specific risk\u2013benefit\u2014to support reproducible and clinically interpretable therapeutic development.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1841160","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:56:57Z","timestamp":1785844617000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Delivery platforms for in vivo CAR-T engineering"],"prefix":"10.3389","volume":"17","author":[{"given":"He","family":"Wang","sequence":"first","affiliation":[{"name":"Clinical Laboratory, Second Affiliated Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangmei","family":"Qiao","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Second Affiliated Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Huangyuan County People\u2019s Hospital","place":["Xining, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Huangyuan County People\u2019s Hospital","place":["Xining, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Luo","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Second Affiliated Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Second Affiliated Hospital of Dalian Medical 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