2023年是RNAi发现25周年。基于RNAi的疗法通过互补碱基配对消除靶RNA分子来实现序列特异性基因敲除。对已发表和正在进行的临床试验进行了系统评价。WebofScience,PubMed,和Embase从1998年1月1日至2022年12月30日进行了使用RNAi的临床试验。纳入后,根据预定义的协议从文章中提取数据.共包括发表在81篇文章中的90项试验。此外,正在进行的临床试验是从ClinicalTrials.gov获得的,结果纳入了48项试验。我们调查了基于RNAi的疗法的成熟和递送平台的发展,管理路线,和潜在的目标塑造了临床应用RNAi的当前景观。值得注意的是,大多数当代临床试验使用N-乙酰半乳糖胺递送和皮下给药或脂质纳米颗粒递送和静脉内给药。总之,在过去的十年中,RNAi疗法获得了巨大的动力,导致五种批准的针对肝脏的治疗严重疾病的疗法,正在进行的试验所描绘的轨迹强调,在未来几年中,甚至更多的基于RNAi的药物也可能针对肝外组织。
The year 2023 marks the 25th anniversary of the discovery of
RNAi.
RNAi-based therapeutics enable sequence-specific gene knockdown by eliminating target RNA molecules through complementary base-pairing. A systematic
review of published and ongoing clinical trials was performed. Web of Science, PubMed, and Embase were searched from January 1, 1998, to December 30, 2022 for clinical trials using
RNAi. Following inclusion, data from the articles were extracted according to a predefined protocol. A total of 90 trials published in 81 articles were included. In addition, ongoing clinical trials were retrieved from ClinicalTrials.gov, resulting in the inclusion of 48 trials. We investigated how maturation of RNAi-based therapeutics and developments in delivery platforms, administration routes, and potential targets shape the current landscape of clinically applied
RNAi. Notably, most contemporary clinical trials used either N-acetylgalactosamine delivery and subcutaneous administration or lipid nanoparticle delivery and intravenous administration. In conclusion, RNAi therapeutics have gained great momentum during the past decade, resulting in five approved therapeutics targeting the liver for treatment of severe diseases, and the trajectory depicted by the ongoing trials emphasizes that even more RNAi-based medicines also targeting extra-hepatic tissues are likely to be available in the years to come.