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重编程 RNA 加工:一个新兴的治疗领域。

Reprogramming RNA processing: an emerging therapeutic landscape.

机构信息

Remix Therapeutics, Cambridge, MA, USA.

Remix Therapeutics, Cambridge, MA, USA.

出版信息

Trends Pharmacol Sci. 2022 May;43(5):437-454. doi: 10.1016/j.tips.2022.02.011. Epub 2022 Mar 21.

Abstract

The production of a mature mRNA requires coordination of multiple processing steps, which ultimately control its content, localization, and stability. These steps include some of the largest macromolecular machines in the cell, which were, until recently, considered undruggable due to their biological complexity. Building from an expanded understanding of the underlying mechanisms that drive these processes, a new wave of therapeutics is seeking to target RNA processing. With a focus on impacting gene regulation at the RNA level, such modalities offer potential for sequence-specific resolution in drug design. Here, we review our current understanding of RNA-processing events and their role in gene regulation, with a focus on the therapeutic opportunities that have emerged within this landscape.

摘要

成熟 mRNA 的产生需要多个加工步骤的协调,这些步骤最终控制其含量、定位和稳定性。这些步骤包括细胞中一些最大的大分子机器,由于其生物复杂性,直到最近才被认为是不可成药的。基于对驱动这些过程的基础机制的扩展理解,一波新的治疗方法正试图针对 RNA 加工。这些方法侧重于在 RNA 水平上影响基因调控,为药物设计提供了潜在的序列特异性分辨率。在这里,我们回顾了我们对 RNA 加工事件及其在基因调控中的作用的现有理解,重点介绍了这一领域出现的治疗机会。

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