{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:07:58Z","timestamp":1792789678337,"version":"4.5.0"},"reference-count":97,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2023YFC3504300"],"award-info":[{"award-number":["2023YFC3504300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural Science Foundation of China","award":["82371480"],"award-info":[{"award-number":["82371480"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82073340"],"award-info":[{"award-number":["82073340"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"award":["82371480"],"award-info":[{"award-number":["82371480"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82073340"],"award-info":[{"award-number":["82073340"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2023A1515011148"],"award-info":[{"award-number":["2023A1515011148"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2024A1515013046"],"award-info":[{"award-number":["2024A1515013046"]}]},{"name":"Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders","award":["2023B1212120004"],"award-info":[{"award-number":["2023B1212120004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Aptamers are short nucleic acid molecules that bind to targets with high specificity. Recognized as \u201cchemical antibodies\u201d, they offer distinct advantages including strong programmability and ease of synthesis and chemical modification. Heterobifunctional targeted degraders were developed to address the challenges posed by traditionally \u201cundruggable\u201d targets and acquired drug resistance. The degraders recruit endogenous cellular degradation machinery to catalyze the removal of disease-associated proteins, thereby overcoming the limitations of conventional occupancy-driven inhibition. The fusion of aptamers with these degradation modalities has given rise to integrated platforms such as aptamer\u2013proteolysis-targeting chimeras (PROTACs), aptamer\u2013lysosome-targeting chimeras (LYTACs), and aptamer\u2013autophagosome-tethering compounds (ATTECs). These conjugates combine the precise targeting ability of aptamers with the event-driven, catalytic nature of degradation technologies. As such, they not only expand the druggable target space to include intracellular proteins, membrane proteins, and pathogenic aggregates but also hold significant therapeutic potential in areas ranging from oncology and neurodegenerative disorders to infections and inflammatory diseases. Furthermore, degradation can be spatially and temporally controlled through receptor-mediated delivery or photo-switchable mechanisms. In this review, we provide a comprehensive summary of recent progress in studies on aptamer-based heterobifunctional degraders, with an emphasis on their design principles, biomedical applications, and therapeutic prospects.<\/jats:p>","DOI":"10.3390\/molecules31183318","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:12:09Z","timestamp":1789999929000},"page":"3318","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aptamer-Based Heterobifunctional Targeted Degraders in Disease Treatment"],"prefix":"10.3390","volume":"31","author":[{"given":"Xiuhua","family":"Liang","sequence":"first","affiliation":[{"name":"Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghan","family":"Du","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Lei","sequence":"additional","affiliation":[{"name":"First School of Clinical Medicine, The First Affiliated Hospital, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghong","family":"Tian","sequence":"additional","affiliation":[{"name":"Experiment Teaching & Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9548-1289","authenticated-orcid":false,"given":"Xingmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1126\/science.2200121","article-title":"Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage t4 DNA polymerase","volume":"249","author":"Tuerk","year":"1990","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.omtn.2018.07.008","article-title":"Selection of metastatic breast cancer cell-specific aptamers for the capture of CTCs with a metastatic phenotype by cell-selex","volume":"12","author":"Li","year":"2018","journal-title":"Mol. 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