Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases, Hangzhou, Zhejiang, China.
Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases, Hangzhou, Zhejiang, China; Department of Neurosurgery, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, Zhejiang, China.
Eur J Pharmacol. 2023 Oct 5;956:175956. doi: 10.1016/j.ejphar.2023.175956. Epub 2023 Aug 2.
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.
miRNA（miRNA）介导的基因沉默是一种 RNA 干扰方法，其中 miRNA 与信使 RNA 序列结合并调节靶基因表达。基于 miRNA 的治疗方法已在治疗多种中枢神经系统疾病方面显示出前景，这已被来自不同临床前模式生物的结果所证实。在过去十年中，已有几种基于 miRNA 的治疗方法进入了各种疾病（如肿瘤、感染和遗传性疾病）的临床试验。然而，针对中枢神经系统疾病的临床试验却很少，许多中枢神经系统疾病，包括脑出血、脑缺血、脑外伤、顽固性癫痫和阿尔茨海默病，缺乏有效治疗方法。鉴于其在临床前实验中对中枢神经系统疾病的有效性，基于 miRNA 的干预可能成为治疗这些疾病的一种有前途的方法。本文综述了基于 miRNA 的治疗的基本原则和最新进展，并总结了开发用于治疗中枢神经系统疾病的此类治疗方法的一般程序。然后，讨论了药物开发中的当前障碍。这篇综述还为未来解决这些障碍提供了新的视角。
