The vast majority of the human genome codes for RNA, but RNA-targeting therapeutics account for a small fraction of approved drugs. As such, there is great incentive to improve old and develop new approaches to RNA targeting. For many RNA targeting modalities, just binding is not sufficient to exert a therapeutic effect; thus, targeted RNA degradation and induced decay emerged as powerful approaches with a pronounced biological effect. This review covers the origins and advanced use cases of targeted RNA degrader technologies grouped by the nature of the targeting modality as well as by the mode of degradation. It covers both well-established methods and clinically successful platforms such as RNA interference, as well as emerging approaches such as recruitment of RNA quality control machinery, CRISPR, and direct targeted RNA degradation. We also share our thoughts on the biggest hurdles in this field, as well as possible ways to overcome them.

中文翻译：

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靶向 RNA 降解和诱导 RNA 衰变的技术


绝大多数人类基因组编码 RNA，但 RNA 靶向疗法只占已批准药物的一小部分。因此，有很大的动力来改进旧的 RNA 靶向方法并开发新的方法。对于许多 RNA 靶向方式，仅结合不足以发挥治疗效果;因此，靶向 RNA 降解和诱导衰变成为具有显着生物学效应的强大方法。本综述涵盖了靶向 RNA 降解剂技术的起源和高级用例，按靶向方式的性质和降解方式分组。它涵盖了成熟的方法和临床成功的平台，例如 RNA 干扰，以及新兴方法，例如 RNA 质量控制机制的募集、CRISPR 和直接靶向 RNA 降解。我们还分享了我们对该领域最大障碍的看法，以及克服这些障碍的可能方法。