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However, the cell plasma membrane prevents the entry of almost all free genome\u2010manipulation agents. Therefore, a system can be spatiotemporally controlled and can instantly open the cellular membrane to allow the entry of genome\u2010editing agents into target cells is needed. Here, inspired by the ability of T cells to deliver cytotoxins to cancer cells by perforation, an ultrasound (US)\u2010controlled perforation system (UPS) is established to enhance the delivery of free genome\u2010manipulating agents. The UPS can perforate the tumor cell membrane while maintaining cell viability via a controllable lipid peroxidation reaction. In vitro, transmembrane\u2010incapable plasmids can enter cells and perform genome editing with the assistance of UPS, achieving an efficiency of up to 90%. In vivo, the UPS is biodegradable, nonimmunogenic, and tumor\u2010targeting, enabling the puncturing of tumor cells under US. With the application of UPS\u2010assisted genome editing, gasdermin\u2010E expression in 4T1 tumor\u2010bearing mice is successfully restored, which leads to pyroptosis\u2010mediated antitumor immunotherapy via low\u2010dose X\u2010ray irradiation. This study provides new insights for designing a sonoporation system for genome editing. Moreover, the results demonstrate that restoring gasdermin expression by genome editing significantly improves the efficacy of radioimmunotherapy.<\/jats:p>","DOI":"10.1002\/adma.202401384","type":"journal-article","created":{"date-parts":[[2024,3,24]],"date-time":"2024-03-24T04:19:40Z","timestamp":1711253980000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A T\u2010Cell Inspired Sonoporation System Enhances Low\u2010Dose X\u2010Ray\u2010Mediated Pyroptosis and Radioimmunotherapy Efficacy by Restoring Gasdermin\u2010E Expression"],"prefix":"10.1002","volume":"36","author":[{"given":"Hao","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Radiation and Medical Oncology Wenzhou Key Laboratory of Basic Science and Translational Research of Radiation Oncology Zhejiang Engineering Research Center for Innovation and Application of Intelligent Radiotherapy Technology The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang 325035 P. 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