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Herein, a genetically engineered adenovirus is developed as the vector to deliver CRISPR\/Cas9 (sgCas9\u2010AdV) to achieve permanent PD\u2010L1 gene editing with efficiency up to 78.7% exemplified in Hepa 1\u20106 liver cancer cells. Furthermore, the sgCas9\u2010AdV is loaded into hydrogel made by silk fiber (SgCas9\u2010AdV\/Gel) for in vivo application. The silk\u2010gel not only promotes local retention of sgCas9\u2010AdV in tumor tissue, but also masks them from host immune system, thus ensuring effectively gene transduction over 9 days. Bearing these advantages, the sgCas9\u2010AdV\/Gel inhibits Hepa 1\u20106 tumor growth with 100% response rate by single\u2010dose injection, through efficient PD\u2010L1 disruption to elicit a T cell\u2010mediated antitumor response. In addition, the sgCas9\u2010AdV\/Gel is also successfully extended into other refractory tumors. In CT26 colon tumor characterized by poor response to anti\u2010PD\u2010L1, sgCas9\u2010AdV\/Gel is demonstrated to competent and superior anti\u2010PD\u2010L1 antibody to suppress tumor progression. In highly aggressive orthotopic 4T1 mouse breast tumor, such a therapeutic paradigm significantly inhibits primary tumor growth and induces a durable immune response against tumor relapse\/metastasis. Thus, this study provides an attractive and universal strategy for immunotherapy.<\/jats:p>","DOI":"10.1002\/advs.202206399","type":"journal-article","created":{"date-parts":[[2023,2,25]],"date-time":"2023-02-25T08:20:41Z","timestamp":1677313241000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Silk\u2010Gel Powered Adenoviral Vector Enables Robust Genome Editing of PD\u2010L1 to Augment Immunotherapy across Multiple Tumor Models"],"prefix":"10.1002","volume":"10","author":[{"given":"Ming","family":"Wu","sequence":"first","affiliation":[{"name":"The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University  Fuzhou 350025 P. R. China"},{"name":"The Liver Center of Fujian Province Fujian Medical University  Fuzhou 350025 P. R. China"},{"name":"Mengchao Med\u2010X Center Fuzhou University  Fuzhou 350116 P. R. 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