mRNA药物稳定性研究进展  

Research Progress on the Stability of mRNA Drugs

作　　者：黄奡 冉丽 熊长云 王友如 HUANG Ao;RAN Li;XIONG Changyun;WANG Youru(Ningbo Junjian Biotechnologies Co.,Ltd.,Ningbo 315832,China;School of Life Sciences,Hubei Normal University Huangshi 435002,China;School of Basic Medical Sciences and Forensic Medicine,Hangzhou Medical College/Zhejiang Engineering Research Center for New Vaccines,Hangzhou 310000,China)

机构地区：[1]宁波君健生物科技有限公司,浙江宁波315832 [2]湖北师范大学生命科学学院,湖北黄石435002 [3]杭州医学院基础医学院与法医学学院/新型疫苗浙江省工程研究中心,杭州310000

出　　处：《中国现代应用药学》2024年第18期2528-2539,共12页Chinese Journal of Modern Applied Pharmacy

摘　　要：mRNA药物在疾病预防和治疗方面具有潜力,但稳定性问题仍是其广泛应用的主要障碍。本文从mRNA药物的底层化学结构原理出发,详细介绍了mRNA的化学结构、5’帽子、非翻译区、开放阅读框(open reading frame,ORF)和poly(A)尾巴对稳定性的影响,并提出通过优化序列设计和采用修饰核苷来提高mRNA的稳定性。讨论了目前m RNA药物主流的脂质纳米粒(lipid nanoparticle,LNP)递送系统的组成及其在生产、储存和运输中的稳定性问题,并提出了优化LNP设计和生产工艺以提高稳定性的措施;提出了mRNA药物稳定性的评估方法,介绍了mRNA药物的质控方法和法规。mRNA drugs have the potential in disease prevention and treatment,but stability issues remain the main barrier to their widespread application.Based on the underlying chemical structure principles of mRNA drugs,this article provided a detailed introduction to the impact of the chemical structure of mRNA,5’cap,untranslated region,open reading frame(ORF),and poly(A)tail on stability,and suggested improving mRNA stability through optimized sequence design and the use of modified nucleosides.It was discussed that the composition of the mainstream lipid nanoparticle(LNP)delivery system for mRNA drugs,and its stability issues in production,storage,and transportation,and proposes measures to optimize LNP design and manufacturing processes to enhance stability.It was presented that methods for assessing the stability of mRNA drugs,quality control methods for mRNA drugs and regulations were also discussed.

关 键 词：MRNA 脂质纳米粒 稳定性 质量控制 生物化学 

分 类 号：R945[医药卫生—微生物与生化药学]