Beyond canonical PROTAC: biological targeted protein degradation (bioTPD).

IF 11.3 1区 医学 Q1 Medicine
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
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引用次数: 0

Abstract

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 destruction machinery. The exploration and discovery of cellular degradation pathways, including but not limited to proteasomes and lysosome pathways as well as their degraders, is an area of active research. Since the concept of proteolysis-targeting chimeras (PROTACs) was introduced in 2001, the paradigm of TPD has been greatly expanded and moved from academia to industry for clinical translation, with small-molecule TPD being particularly represented. As an indispensable part of TPD, biological TPD (bioTPD) technologies including peptide-, fusion protein-, antibody-, nucleic acid-based bioTPD and others have also emerged and undergone significant advancement 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 their compositional features and potential applications, and briefly discuss their drawbacks. Moreover, we present some strategies to improve the delivery efficacy of bioTPD, addressing their challenges in further clinical development.

Abstract Image

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超越经典PROTAC:生物靶向蛋白降解(bioTPD)。
靶向蛋白降解(TPD)是一种新兴的治疗策略,通过使用宿主破坏机制,有可能调节以前被认为不可治疗的疾病相关蛋白。探索和发现细胞降解途径,包括但不限于蛋白酶体和溶酶体途径及其降解物,是一个积极研究的领域。自2001年引入蛋白水解靶向嵌合体(PROTACs)的概念以来,TPD的范式已经得到了极大的扩展,并从学术界转移到了工业界进行临床翻译,其中小分子TPD尤其具有代表性。作为TPD不可或缺的一部分,近年来,包括肽、融合蛋白、抗体、核酸等在内的生物TPD(bioTPD)技术也出现并取得了重大进展,显示出了超越常规小分子TPD的独特和有前景的活性。在这篇综述中,我们概述了生物TPD技术的最新进展,总结了它们的组成特征和潜在应用,并简要讨论了它们的缺点。此外,我们提出了一些提高生物TPD递送效率的策略,以应对其在进一步临床开发中的挑战。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biomaterials Research
Biomaterials Research Medicine-Medicine (miscellaneous)
CiteScore
10.20
自引率
3.50%
发文量
63
审稿时长
30 days
期刊介绍: Biomaterials Research, the official journal of the Korean Society for Biomaterials, is an open-access interdisciplinary publication that focuses on all aspects of biomaterials research. The journal covers a wide range of topics including novel biomaterials, advanced techniques for biomaterial synthesis and fabrication, and their application in biomedical fields. Specific areas of interest include functional biomaterials, drug and gene delivery systems, tissue engineering, nanomedicine, nano/micro-biotechnology, bio-imaging, regenerative medicine, medical devices, 3D printing, and stem cell research. By exploring these research areas, Biomaterials Research aims to provide valuable insights and promote advancements in the biomaterials field.
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