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Bacterial outer membrane vesicles (OMVs) can activate immunity and deliver therapeutic agents for immunotherapy. However, efficiently targeting and packaging therapeutic molecules into OMVs remains challenging. Here, the engineered\n                    <jats:italic>E. coli<\/jats:italic>\n                    BL21\u2010derived OMVs enable the packaging of multiple genes, resulting in a 7\u2010fold increase in DNA enrichment efficiency and gene silencing in vitro. Moreover, the engineered OMVs carrying genes encoding CXCL9 and IL12 (OMV\u2010C9I12) reprogram tumor cells to secrete these factors, significantly enhancing T\u2010cell chemotaxis and activation. More importantly, this system markedly inhibits tumors, extends survival, and synergizes with anti\u2010PD\u20101\/PD\u2010L1 therapy in murine MB49 and B16F10 tumor models. Single\u2010cell RNA sequencing (scRNA\u2010seq) further reveals significant upregulation of T\u2010cell chemotaxis and activation\u2010related pathways following OMV\u2010C9I12 treatment. Finally, OMV\u2010C9I12 potentiates T cell\u2010mediated immunotherapy and suppresses the growth of bladder and breast cancer tumors in humanized mouse models. These findings highlight the potential of this engineered OMV platform for cancer gene therapy and provide novel strategies to overcome resistance to immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/adma.202501565","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T04:04:23Z","timestamp":1749614663000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Engineering CRISPR System\u2010Based Bacterial Outer Membrane Vesicle Potentiates T Cell Immunity for Enhanced Cancer Immunotherapy"],"prefix":"10.1002","volume":"37","author":[{"given":"Hongjin","family":"Wang","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Department of Urology Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou Guangdong 510120 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