Given that many small molecules could bind to structured regions at sites that will not affect function, approaches that trigger degradation of RNA could provide a general way to affect biology. Indeed, targeted RNA degradation is an effective strategy to selectively and potently modulate biology. We describe several approaches to endow small molecules with the power to cleave RNAs. Central to these strategies is Inforna, which designs small molecules targeting RNA from human genome sequence. Inforna deduces the uniqueness of a druggable pocket, enables generation of hypotheses about functionality of the pocket, and defines on- and off-targets to drive compound optimization. RNA-binding compounds are then converted into cleavers that degrade the target directly or recruit an endogenous nuclease to do so. Cleaving compounds have significantly contributed to understanding and manipulating biological functions. Yet, there is much to be learned about how to affect human RNA biology with small molecules.

中文翻译：

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小干扰RNA的小分子等价物的开发进展。

鉴于许多小分子可以与不影响功能的结构区域结合，引发 RNA 降解的方法可以提供一种影响生物学的通用方法。事实上，靶向 RNA 降解是选择性和有效调节生物学的有效策略。我们描述了几种赋予小分子裂解 RNA 能力的方法。这些策略的核心是 Infona，该公司设计了针对人类基因组序列 RNA 的小分子。Infona 推断出可成药口袋的独特性，能够生成有关口袋功能的假设，并定义目标和脱靶以推动化合物优化。然后，RNA 结合化合物被转化为切割器，直接降解靶标或招募内源性核酸酶来降解靶标。裂解化合物对理解和操纵生物功能做出了重大贡献。然而，关于如何用小分子影响人类 RNA 生物学，还有很多东西需要了解。