Although we live in the remnants of an RNA world, the world of drug discovery and chemical probes is firmly protein-centric. Developing highly selective small molecules targeting RNA is often considered to be an insurmountable challenge. Our goal is to demystify the design of such compounds. In this review, we describe various approaches to design small molecules that target RNA from sequence and the application of these compounds in RNA biology, with a focus on inhibition of human RNA-protein complexes. We have developed a library-versus-library screening approach to define selective RNA-small-molecule binding partners and applied them to disease-causing RNAs, in particular noncoding oncogenic RNAs and expanded RNA repeats, to modulate their biology in cells and animals. We also describe the design of new types of small-molecule probes that could broadly decipher the mysteries of RNA in cells.

中文翻译：

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毒品RNA世界。

尽管我们生活在RNA世界的遗迹中，但药物发现和化学探针的世界坚决以蛋白质为中心。通常认为开发靶向RNA的高选择性小分子是一项不可克服的挑战。我们的目标是揭开这类化合物的神秘面纱。在这篇综述中，我们描述了多种设计小分子的方法，这些小分子可从序列中靶向RNA，并将这些化合物应用到RNA生物学中，重点是抑制人类RNA-蛋白质复合物。我们已经开发了一种库对库筛选方法，以定义选择性的RNA小分子结合伴侣，并将其应用于引起疾病的RNA，特别是非编码致癌RNA和扩增的RNA重复序列，以调节其在细胞和动物中的生物学特性。