mRNA疗法:过去、现在和未来  

mRNA Therapy:Past,Present and Future

作　　者：孙梦泽 李鹏翠[2] 胡晓青[1] SUN Meng-Ze;LI Peng-Cui;HU Xiao-Qing(Department of Sports Medicine,Peking University Third Hospital,Institute of Sports Medicine of Peking University,Beijing Key Laboratory of Sports Injuries,Beijing 100191,China;Department of Orthopedics,The Second Hospital of Shanxi Medical University,Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair,Taiyuan 030001,China)

机构地区：[1]北京大学第三医院运动医学科,北京大学运动医学研究所,运动医学关节伤病北京市重点实验室,北京100191 [2]山西医科大学第二医院骨科,骨与软组织损伤修复山西省重点实验室,太原030001

出　　处：《中国生物化学与分子生物学报》2025年第2期178-189,共12页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金联合基金项目(No.U23A6009)资助。

摘　　要：信使mRNA(messenger RNA,mRNA)疗法是通过将效应分子以mRNA的形式递送至细胞内以治疗疾病的方法。mRNA各个部分序列高度可变的特点为高通量药物开发以及个性化治疗提供了潜在解决方案。本文从mRNA发展历程切入,概述了mRNA的发现发展及其递送方法的演进过程。并针对mRNA所递送蛋白质的不同,分类别介绍mRNA在蛋白质替代疗法、癌症治疗、在体基因编辑和传染病预防中的应用。为将mRNA制剂应用于临床,需针对mRNA及其递送载体进行优化十分关键。本文进一步介绍如何通过核苷修饰和序列优化等方法提高mRNA的翻译效率以及稳定性,并系统比较新型环状mRNA与传统线性mRNA在疫苗开发方面的优劣。同时,针对mRNA的不同递送系统,本文总结脂质纳米颗粒等常用的递送手段,并详细阐述各个方法在靶向递送方面的最新进展。针对目前上市和在研的mRNA药物,本文系统总结其治疗的疾病、递送的效应分子以及所处的临床阶段。最后,本文展望了目前mRNA疗法所面临的问题以及能够潜在治疗的疾病,以期为mRNA疗法开发提供理论基础和参考依据。mRNA therapy involves delivering target molecules in the form of mRNA into cells to treat diseases.The highly variable nature of mRNA sequences offers potential solutions for high-throughput drug discovery and personalized treatment.This review begins with an overview of the development history of mRNA,tracing its journey from discovery to becoming a potential treatment.The review also discusses the applications of mRNA in protein replacement therapy,cancer treatment,in vivo gene editing,and infectious disease prevention based on the different categories of proteins delivered by mRNA.Additionally,optimizing mRNA formulations and their delivery vehicles is crucial for clinical application.This review further explains how to enhance the translation efficiency and stability of mRNA through nucleoside modifications and sequence optimization,and we systematically compare the pros and cons of novel circular mRNA versus traditional linear mRNA in vaccine development.Moreover,we summarize common delivery methods,such as lipid nanoparticles,and discuss the latest advancements in targeted delivery systems.For currently approved and in-development mRNA drugs,we systematically review the diseases treated,effector molecules delivered,and their clinical stages.Finally,we explore the challenges facing mRNA therapies and the potential diseases they could address,aiming to provide a theoretical foundation and reference for the development of mRNA therapies.

关 键 词：信使核糖核酸 mRNA递送 mRNA疗法 

分 类 号：Q78[生物学—分子生物学]