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Beyond Canonical PROTAC: Biological targeted protein degradation (bioTPD)
Huifang Wang,Runhua Zhou,Fushan Xu,Kongjun Yang,Liuhai Zheng,Pan Zhao,Guangwei Shi,Lingyun Dai,Chengchao Xu,Le Yu,Zhijie Li,Jianhong Wang,Jigang Wang 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00
Targeted protein degradation (TPD) is an emerging therapeutic strategy with the potential to modulate disease associated proteins that have previously been considered undruggable, by employing the host destructionmachinery. The exploration and discovery of cellular degradation pathways, including but not limited toproteasomes and lysosome pathways as well as their degraders, is an area of active research. Since the conceptof proteolysis-targeting chimeras (PROTACs) was introduced in 2001, the paradigm of TPD has been greatlyexpanded and moved from academia to industry for clinical translation, with small-molecule TPD being particularlyrepresented. As an indispensable part of TPD, biological TPD (bioTPD) technologies including peptide-, fusionprotein-, antibody-, nucleic acid-based bioTPD and others have also emerged and undergone significantadvancement in recent years, demonstrating unique and promising activities beyond those of conventional small molecule TPD. In this review, we provide an overview of recent advances in bioTPD technologies, summarize theircompositional features and potential applications, and briefly discuss their drawbacks. Moreover, we present somestrategies to improve the delivery efficacy of bioTPD, addressing their challenges in further clinical development.
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