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In contrast to traditional \u201coccupancy-driven\u201d inhibition approaches, these technologies ingeniously leverage the cell\u2019s endogenous degradation mechanisms to achieve specific elimination of disease-causing targets. Autophagy, a highly conserved cellular clearance pathway, possesses broad substrate recognition capabilities, enabling degradation of not only individual proteins but also protein aggregates, damaged organelles, and invading pathogens. Given these characteristics, researchers are actively exploring the application of autophagy mechanisms in targeted degradation technologies. Herein, we summarize recent advances in autophagy-dependent degradation approaches, including autophagosome tethering compounds (ATTEC), autophagy-targeting chimeras (AUTAC), autophagy-targeting Chimera (AUTOTAC), chaperone-mediated autophagy (CMA)-based methods, nanotechnology-based strategies, and the newly introduced autophagy-induced antibody (AUTAB) technique, highlighting their mechanisms, advantages, and potential applications in treating tumors, neurodegenerative diseases, and other challenging conditions.<\/jats:p>","DOI":"10.3390\/ijms26146576","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T12:46:33Z","timestamp":1752237993000},"page":"6576","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Targeted Degradation Technologies Utilizing Autophagy"],"prefix":"10.3390","volume":"26","author":[{"given":"Zeyu","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518000, China"},{"name":"Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518028, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaming","family":"Liang","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binghua","family":"Cheng","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518000, China"},{"name":"Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518028, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518000, China"},{"name":"Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518028, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Shi","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Liu","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518028, China"},{"name":"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijing","family":"Fang","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518028, China"},{"name":"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchang","family":"Li","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518028, China"},{"name":"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4520-3393","authenticated-orcid":false,"given":"Ximing","family":"Shao","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/s41568-021-00365-x","article-title":"Advancing targeted protein degradation for cancer therapy","volume":"21","author":"Dale","year":"2021","journal-title":"Nat. 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