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However, manufacturing with integrating viral vectors is costly, slow, and carries risks including insertional mutagenesis, prolonged B cell aplasia, and other long-term toxicities. Expression of CAR with mRNA can reduce cost, manufacturing timelines, and improve safety. However, the short-lived expression necessitates frequent repeat dosing. Here, we describe a modified self-amplifying RNA (saRNA) platform for engineering CAR T cells with prolonged CAR expression and enhanced durability of tumor control relative to mRNA CAR T cells. In an acute lymphoblastic leukemia (ALL) xenograft model, saRNA CAR T cells achieve superior tumor suppression and prolong survival. Further, a single-strand modified saRNA supports the co-expression of multiple proteins, enabling the construction of advanced CAR systems, such as OR- and AND-gated logic CAR T cells. Together, these results highlight saRNA as a powerful and versatile platform for CAR T cell engineering with favorable safety, efficacy, and accessibility.<\/jats:p>","DOI":"10.64898\/2026.02.18.706661","type":"posted-content","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T17:30:14Z","timestamp":1771608614000},"source":"Crossref","is-referenced-by-count":2,"title":["Self-amplifying RNA-based CAR T cell therapy with enhanced duration and multi-genic logic functions"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7783-9002","authenticated-orcid":false,"given":"Yuyang","family":"Gu","sequence":"first","affiliation":[{"name":"Division of Materials Science & Engineering, Boston University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8938-1821","authenticated-orcid":false,"given":"Jaehoon","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Boston University, Boston, MA, USA"},{"name":"Biological Design Center, Boston University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6271-4293","authenticated-orcid":false,"given":"Devin","family":"Mutha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Biophysics, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0483-418X","authenticated-orcid":false,"given":"Christopher","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Boston University, Boston, MA, USA"},{"name":"Biological Design Center, Boston University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0269-6585","authenticated-orcid":false,"given":"Neil J.","family":"Ganem","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Biophysics, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5453-3668","authenticated-orcid":false,"given":"Mark W.","family":"Grinstaff","sequence":"additional","affiliation":[{"name":"Division of Materials Science & Engineering, Boston University, Boston, MA, USA"},{"name":"Department of Biomedical Engineering, Boston University, Boston, MA, USA"},{"name":"Department of Chemistry, Boston University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8394-889X","authenticated-orcid":false,"given":"Wilson W.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Boston University, Boston, MA, USA"},{"name":"Biological Design Center, Boston University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026032408051192000_2026.02.18.706661v2.1","doi-asserted-by":"crossref","unstructured":"I. 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