New biological tools provide new techniques to probe fundamental biological processes. Here we describe the burgeoning field of proteolysis-targeting chimeras (PROTACs), which are capable of modulating protein concentrations at a post-translational level by co-opting the ubiquitin-proteasome system. We describe the PROTAC technology and its application to drug discovery and provide examples where PROTACs have enabled novel biological insights. Furthermore, we provide a workflow for PROTAC development and use and discuss the benefits and issues associated with PROTACs. Finally, we compare PROTAC-mediated protein-level modulation with other technologies, such as RNAi and genome editing.

中文翻译：

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靶向蛋白水解嵌合体作为生物发现的治疗手段和工具。

新的生物学工具提供了探索基本生物学过程的新技术。在这里，我们描述了靶向蛋白水解嵌合体（PROTAC）的新兴领域，该领域能够通过选择泛素-蛋白酶体系统来调节翻译后水平的蛋白质浓度。我们描述了PROTAC技术及其在药物发现中的应用，并提供了一些实例，其中PROTAC带来了新颖的生物学见解。此外，我们提供了PROTAC开发和使用的工作流程，并讨论了与PROTAC相关的收益和问题。最后，我们将PROTAC介导的蛋白质水平调节与其他技术（例如RNAi和基因组编辑）进行了比较。