微小RNA（miRNA）介导的基因沉默是一种RNA干扰的方法，其中miRNA结合到信使RNA序列，并调节靶基因表达。miRNA基因治疗在治疗多种中枢神经系统疾病方面显示出潜力，这一点由不同的临床前模型生物的结果所证实。过去十年中，已有几种基于miRNA的治疗方法进入了治疗不同种类疾病的临床试验，如肿瘤、感染和遗传疾病。然而，中枢神经系统疾病的诊疗临床试验相对较少，包括出血性和缺血性中风、创伤性脑损伤、难治性癫痫和阿尔茨海默病等很多中枢神经系统疾病缺乏有效治疗方法。考虑到对中枢神经系统疾病的治疗在临床前实验中的有效性，基于微小RNA的干预可能作为这些疾病的一种有希望的治疗方法。本论文回顾了基于miRNA的疗法的基本原理和最新进展，并总结了开发此类治疗方法用于治疗中枢神经系统疾病的一般程序。然后，讨论了药物研发中的当前障碍。本综述还对未来解决这些障碍的可能解决方案提供了新的观点。版权所有 © 2023。由Elsevier B.V.出版。

MicroRNA (miRNA)-mediated gene silencing is a method of RNA interference in which a miRNA binds to messenger RNA sequences and regulates target gene expression. MiRNA-based therapeutics have shown promise in treating a variety of central nervous system diseases, as verified by results from diverse preclinical model organisms. Over the last decade, several miRNA-based therapeutics have entered clinical trials for various kinds of diseases, such as tumors, infections, and inherited diseases. However, such clinical trials for central nervous system diseases are scarce, and many central nervous system diseases, including hemorrhagic stroke, ischemic stroke, traumatic brain injury, intractable epilepsy, and Alzheimer's disease, lack effective treatment. Considering its effectiveness for central nervous system diseases in preclinical experiments, microRNA-based intervention may serve as a promising treatment for these kinds of diseases. This paper reviews basic principles and recent progress of miRNA-based therapeutics and summarizes general procedures to develop such therapeutics for treating central nervous system diseases. Then, the current obstacles in drug development are discussed. This review also provides a new perspective on possible solutions to these obstacles in the future.Copyright © 2023. Published by Elsevier B.V.