RNA化学与治疗学。

RNA chemistry and therapeutics.

作者信息

Wang Siyu, Weissman Drew, Dong Yizhou

机构信息

Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Department of Medicine, Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

出版信息

Nat Rev Drug Discov. 2025 Jul 14. doi: 10.1038/s41573-025-01237-x.

DOI:10.1038/s41573-025-01237-x

PMID:40659813

Abstract

RNA-based therapeutics have made substantial clinical advances, primarily due to the unique chemical and biological profiles of RNA molecules. As evidenced by the approval of various RNA drugs, some initial challenges related to RNA-based therapeutics, including issues associated with large-scale production, effective delivery and immunogenicity properties, are now being addressed. Extensive efforts have focused on chemically modifying RNA molecules to enhance their stability, increase protein production, extend circulation time and improve target specificity. Three RNA categories - small RNA, translatable RNA and CRISPR guide RNA - are now being extensively developed for therapeutic applications. This Review summarizes the synthetic methods applied to these three RNA categories, describes key chemical modification strategies being used to enhance their properties and highlights current therapeutic applications and future opportunities.

摘要

基于RNA的疗法已取得了重大的临床进展，这主要归功于RNA分子独特的化学和生物学特性。各种RNA药物的获批证明，一些与基于RNA的疗法相关的初始挑战，包括与大规模生产、有效递送和免疫原性相关的问题，目前正在得到解决。人们已付出大量努力，致力于对RNA分子进行化学修饰，以增强其稳定性、提高蛋白质产量、延长循环时间并改善靶向特异性。目前，三类RNA——小RNA、可翻译RNA和CRISPR引导RNA——正被广泛开发用于治疗应用。本综述总结了应用于这三类RNA的合成方法，描述了用于增强其特性的关键化学修饰策略，并强调了当前的治疗应用和未来机遇。