RNA has long been an enticing therapeutic target, but is now garnering increased attention, largely driven by clinical successes of RNA interference–based drugs. While gene knockdown by well-established RNA interference– and other oligonucleotide-based strategies continues to advance in the clinic, the repertoire of targetable effectors capable of altering gene expression at the RNA level is also rapidly expanding. In this review, we focus on several recently developed bifunctional molecular technologies that both interact with and act upon a target RNA. These new approaches for programmable RNA knockdown, editing, splicing, translation, and chemical modifications stand to provide impactful new modalities for therapeutic development in the coming decades.

RNA 长期以来一直是一个诱人的治疗靶点，但现在越来越受到关注，这主要是由于基于 RNA 干扰的药物的临床成功。虽然通过成熟的 RNA 干扰和其他基于寡核苷酸的策略进行基因敲除在临床上继续取得进展，但能够在 RNA 水平上改变基因表达的靶向效应器库也在迅速扩大。在这篇综述中，我们专注于最近开发的几种双功能分子技术，它们既能与靶 RNA 相互作用，又能作用于靶 RNA。这些用于可编程 RNA 敲除、编辑、剪接、翻译和化学修饰的新方法将为未来几十年的治疗发展提供有影响力的新模式。