Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Sci China Life Sci. 2020 Apr;63(4):485-500. doi: 10.1007/s11427-018-9438-y. Epub 2019 Apr 30.
Since the revolutionary discovery of RNA interference (RNAi), a remarkable progress has been achieved in understanding and harnessing gene silencing mechanism; especially in small interfering RNA (siRNA) therapeutics. Despite its tremendous potential benefits, major challenges in most siRNA therapeutics remains unchanged-safe, efficient and target oriented delivery of siRNA. Twenty years after the discovery of RNAi, siRNA therapeutics finally charts its way into clinics. As we journey through the decades, we reminisce the history of siRNA discovery and its application in a myriad of disease treatments. Herein, we highlight the breakthroughs in siRNA therapeutics, with special feature on the first FDA approved RNAi therapeutics Onpattro (Patisiran) and the consideration of effective siRNA delivery system focusing on current siRNA nanocarrier in clinical trials. Lastly, we present some challenges and multiple barriers that are yet to be fully overcome in siRNA therapeutics.
自 RNA 干扰（RNAi）的革命性发现以来，人们在理解和利用基因沉默机制方面取得了显著进展；特别是在小干扰 RNA（siRNA）治疗方面。尽管具有巨大的潜在益处，但大多数 siRNA 治疗的主要挑战仍然没有改变——安全、高效和靶向地输送 siRNA。在发现 RNAi 二十年后，siRNA 治疗终于进入了临床阶段。在我们穿越几十年的历程中，我们回顾了 siRNA 的发现历史及其在治疗各种疾病中的应用。在这里，我们重点介绍 siRNA 治疗的突破，特别关注第一个获得 FDA 批准的 RNAi 治疗药物 Onpattro（Patisiran），以及关注目前临床试验中有效的 siRNA 递药系统聚焦于当前的 siRNA 纳米载体。最后，我们提出了 siRNA 治疗中尚未完全克服的一些挑战和多重障碍。
