School of Life Science, Advanced Research Institute of Multidisciplinary Science, Key Laboratory of Molecular Medicine and Biotherapy, Beijing Institute of Technology, Beijing, 100081, P. R. China.
School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, P. R. China.
J Gene Med. 2019 Jul;21(7):e3097. doi: 10.1002/jgm.3097. Epub 2019 Jun 17.
Small interfering RNA (siRNA) enables efficient target gene silencing by employing a RNA interference (RNAi) mechanism, which can compromise gene expression and regulate gene activity by cleaving mRNA or repressing its translation. Twenty years after the discovery of RNAi in 1998, ONPATTRO™ (patisiran) (Alnylam Pharmaceuticals, Inc.), a lipid formulated siRNA modality, was approved for the first time by United States Food and Drug Administration and the European Commission in 2018. With this milestone achievement, siRNA therapeutics will soar in the coming years. Here, we review the discovery and the mechanisms of RNAi, briefly describe the delivery technologies of siRNA, and summarize recent clinical advances of siRNA therapeutics.
小干扰 RNA（siRNA）通过 RNA 干扰（RNAi）机制实现高效的靶基因沉默，该机制可以通过切割 mRNA 或抑制其翻译来干扰基因表达并调节基因活性。在 1998 年发现 RNAi 二十年后，ONPATTRO™（patisiran）（Alnylam Pharmaceuticals，Inc.），一种脂质配方的 siRNA 模式，于 2018 年首次被美国食品和药物管理局和欧洲委员会批准。随着这一里程碑式的成就，siRNA 疗法将在未来几年迅速发展。在这里，我们回顾了 RNAi 的发现和机制，简要描述了 siRNA 的递药技术，并总结了 siRNA 疗法的最新临床进展。
