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Here we develop a DNA\u2010logic CAR (DL\u2010CAR) system that enables programmable targeting and precise ablation of tumors with specific antigen combination patterns. The DL\u2010CAR system is engineered using HaloTag as an extracellular domain for DNA conjugation, which allows controlling the assembly of tumor\u2010targeting aptamers for universal and combinatorial antigen recognition via DNA logic computation. DL\u2010CAR\u2010T cells are shown to be capable of targeting tumor cells with different antigens and controlling the CAR circuit through AND, OR, and INHIBIT Boolean logic for specific T\u2010cell activation and cytolysis. The DL\u2010CAR system demonstrated high efficacy for tumor eradication in mouse models, with the AND\u2010, OR\u2010, and INHIBIT\u2010gated computation affording enhanced selectivity for tumors with specific antigen combinations. DL\u2010CAR may provide a new paradigm to develop programmable CAR\u2010T circuits for precision cancer therapy.<\/jats:p>","DOI":"10.1002\/anie.9420497","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:05:47Z","timestamp":1777449947000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Programmable Chimeric Antigen Receptor T Cell Circuits With DNA Computing for Precision Tumor Therapy"],"prefix":"10.1002","volume":"65","author":[{"given":"Miao","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Chemo and Biosensing College of Chemistry and Chemical Engineering Hunan University  Changsha P. R. 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