RNA interference mediated by small interfering RNAs (siRNAs) has been exploited for the development of therapeutics. siRNAs can be a powerful therapeutic tool because the working mechanisms of siRNAs are straightforward. siRNAs determine targets based on their sequence and specifically regulate the gene expression of the target gene. However, efficient delivery of siRNAs to the target organ has long been an issue that needs to be solved. Tremendous efforts regarding siRNA delivery have led to significant progress in siRNA drug development, and from 2018 to 2022, a total of five siRNA drugs were approved for the treatment of patients. Although all FDA-approved siRNA drugs target the hepatocytes of the liver, siRNA-based drugs targeting different organs are in clinical trials. In this review, we introduce siRNA drugs in the market and siRNA drug candidates in clinical trials that target cells in multiple organs. The liver, eye, and skin are the preferred organs targeted by siRNAs. Three or more siRNA drug candidates are in phase 2 or 3 clinical trials to suppress gene expression in these preferred organs. On the other hand, the lungs, kidneys, and brain are challenging organs with relatively few clinical trials. We discuss the characteristics of each organ related to the advantages and disadvantages of siRNA drug targeting and strategies to overcome the barriers in delivering siRNAs based on organ-specific siRNA drugs that have progressed to clinical trials.

由小干扰 RNA （siRNA） 介导的 RNA 干扰已被用于开发治疗方法。siRNA 可以成为一种强大的治疗工具，因为 siRNA 的工作机制很简单。siRNA 根据其序列确定靶标，并特异性调节靶基因的基因表达。然而，长期以来，将 siRNA 高效递送至靶器官一直是一个需要解决的问题。在 siRNA 递送方面付出的巨大努力使 siRNA 药物开发取得了重大进展，从 2018 年到 2022 年，共有 5 种 siRNA 药物被批准用于治疗患者。尽管所有 FDA 批准的 siRNA 药物都靶向肝脏的肝细胞，但靶向不同器官的基于 siRNA 的药物正处于临床试验中。在这篇综述中，我们介绍了市场上的 siRNA 药物和临床试验中靶向多个器官细胞的 siRNA 候选药物。肝脏、眼睛和皮肤是 siRNA 靶向的首选器官。三种或三种以上的 siRNA 候选药物正处于 2 期或 3 期临床试验中，以抑制这些首选器官中的基因表达。另一方面，肺、肾和大脑是具有挑战性的器官，临床试验相对较少。我们讨论了与 siRNA 药物靶向的优缺点相关的每个器官的特征，以及克服基于已进入临床试验的器官特异性 siRNA 药物递送 siRNA 的障碍的策略。