RNA修饰在mRNA疫苗中的关键应用和前景  

Critical applications and prospects of RNA modification in mRNA vaccines

作　　者：刘聪 彭金英 张美玲 向卉芬[3,4] 伊成器 Cong Liu;Jinying Peng;Meiling Zhang;Huifen Xiang;Chengqi Yi(State Key Laboratory of Protein and Plant Gene Research,School of Life Sciences,Peking University,Beijing 100871,China;Peking-Tsinghua Center for Life Sciences,Beijing 100871,China;Department of Obstetrics and Gynecology,the First Affiliated Hospital of Anhui Medical University,Hefei 230032,China;NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract,Hefei 230032,China;Synthetic and Functional Biomolecules Center,Peking University,Beijing 100871,China;Beijjing Advanced Center of RNA Biology(BEACON),Beijing 100871,China)

机构地区：[1]北京大学生命科学学院,蛋白质与植物基因研究国家重点实验室,北京100871 [2]北大-清华生命科学联合中心,北京100871 [3]安徽医科大学第一附属医院妇产科,合肥230032 [4]国家卫生健康委配子及生殖道异常研究重点实验室,合肥230032 [5]北京大学合成与功能分子生物中心,北京100871 [6]核糖核酸北京研究中心,北京100871

出　　处：《科学通报》2024年第33期4874-4888,共15页Chinese Science Bulletin

基　　金：国家重点研发计划(2021YFC2302400)资助。

摘　　要：RNA修饰是指发生在RNA分子碱基或核糖上的各种化学修饰基团.这些修饰广泛存在于多种天然RNA中,能够改变RNA分子的化学和物理性质,从而影响RNA在细胞内的功能和命运.近年来,mRNA疫苗因其高效、快速设计、成本效益高和相对安全的管理方式,逐渐成为传统疫苗可靠的替代方案.目前,mRNA疫苗的应用范围涵盖了传染病、癌症、免疫性疾病和罕见病治疗等多个领域,展示了mRNA疫苗在不同治疗领域的多功能性和潜力.除了脂质纳米粒子递送技术的进步,RNA修饰在mRNA疫苗的研发过程中也扮演着不可或缺的角色.RNA修饰,如Ψ、m1Ψ和m5C的应用不仅可以极大地降低mRNA疫苗的免疫原性,还有助于提高mRNA疫苗的稳定性和翻译效率.RNA修饰的mRNA疫苗在传染病如寨卡病毒、流感病毒和SARS-CoV-2等方面的重要应用,极大地推动了该领域疫苗的发展.同时,RNA修饰的mRNA疫苗在癌症免疫治疗中也发挥着关键作用.此外,RNA修饰和佐剂在mRNA疫苗中的联合应用在肿瘤mRNA疫苗的开发中显示出显著的效果,为开发既能激发充分免疫反应又具备安全性和有效性的mRNA疫苗提供了有前景的新途径.因此,本文重点分析和总结mRNA疫苗相关RNA修饰的发生、发展及重要性质,介绍它们在mRNA疫苗发展中的关键作用和重要应用,并阐述mRNA疫苗在传染病与癌症等疾病预防和治疗中的应用及最新进展.最后,我们针对RNA修饰的mRNA疫苗目前的研究和应用的局限性,及未来发展的前景与挑战展开详细的讨论.RNA modification refers to various chemical modifications that occur on the nucleotide bases or ribose of RNA molecules.These modifications are common in different natural types of RNA and can alter the chemical and physical properties of RNA molecules,thereby impacting their functions and fate within cells.In recent years,mRNA vaccines have gradually emerged as reliable alternatives to traditional vaccines due to their high efficiency,rapid design,cost-effectiveness,and relative safety upon administration.mRNA vaccines have shown therapeutic efficacy in multiple fields,including infectious diseases,cancers,immunological diseases,and rare diseases.Many mRNA vaccines have successfully progressed through clinical trials and several have garnered official authorization from the FDA,thus demonstrating the versatility and potential of mRNA vaccines in different therapeutic areas.However,their application of mRNA vaccines has been restricted until recently due to their instability and inefficient in vivo delivery of mRNA.Recent technological advances such as the technological advancements in lipid nanoparticle delivery systems have helped overcome these issues.In addition,RNA modifications play an indispensable role in the development of mRNA vaccines.The application of RNA modifications,such asΨ,m1Ψ,and m5 C,not only greatly reduces the immunogenicity of mRNA vaccines but also improves their stability and translation efficiency.The important applications of RNA-modified mRNA vaccines in infectious diseases,such as infections with Zika virus,influenza virus,and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)have greatly facilitated the development of vaccines in this field.Similarly,RNA-modified mRNA vaccines also play a crucial role in cancer immunotherapy.Furthermore,the combination of RNA modifications and adjuvants in mRNAvaccines has shown significant efficacy in tumors,providing a promising new approach for the development of mRNA vaccines that can elicit robust immune responses while ensuring safet

关 键 词：RNA修饰 mRNA疫苗 传染病 癌症 

分 类 号：R392[医药卫生—免疫学]