基于病毒样颗粒的mRNA递送系统研究进展  

Progress in mRNA delivery systems based on virus-like particles

作　　者：王玹 万颖 张先恩 徐承晨[1] 李峰 Xuan Wang;Ying Wan;Xian-En Zhang;Chengchen Xu;Feng Li(College of Life Sciences and Health,Wuhan University of Science and Technology,Wuhan 430065,China;State Key Laboratory of Virology,Wuhan Institute of Virology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan 430071,China;Faculty of Synthetic Biology,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China;National Laboratory of Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 10010l,China)

机构地区：[1]武汉科技大学生命科学与健康学院,武汉430065 [2]中国科学院武汉病毒研究所,生物安全大科学中心,病毒学国家重点实验室,武汉430071 [3]深圳理工大学(筹)合成生物学院,深圳518055 [4]中国科学院生物物理研究所,生物大分子国家重点实验室,北京100101

出　　处：《科学通报》2024年第31期4625-4636,共12页Chinese Science Bulletin

基　　金：湖北省自然科学基金(2023AFD076);湖北省教育厅科研计划(Q20221103);湖北省卫生健康委员会面上项目(WJ2021M214);武汉市知识创新专项(2022020801010146)资助。

摘　　要：近年来,信使核糖核酸(messenger RNA,mRNA)在疫苗研发、蛋白质替代治疗、基因编辑等领域展现出了独特的研究价值和应用前景.受限于m RNA自身的理化特性,如何保证mRNA高效进入靶细胞并翻译一直是mRNA治疗领域要解决的主要问题.开发安全高效的递送系统、提高靶向递送效率仍然是目前研究的热点.病毒是特异、高效的天然核酸递送系统.病毒样颗粒(virus-like particle,VLP)是一种不含病毒基因组的非感染性颗粒,其形态均匀、具有可修饰的内外表面、良好的生物相容性和生物降解性,通过可控自组装能够包装外源核酸,是发展mRNA递送系统的理想候选材料.本文重点概述了无包膜类和包膜类VLP载体在mRNA包装、递送和应用等方面的研究进展,探讨了基于VLP的mRNA递送系统所面临的挑战和机遇,以期为开发新型mRNA递送系统提供参考.In the past few years,the global COVID-19 pandemic has led to widespread attention to mRNA therapy,with the emergence of the m RNA COVID-19 vaccine driving the rapid development of m RNA therapeutics.mRNA has shown great and unique potential in vaccine development,protein replacement therapy,and gene editing,which,however,has been limited by issues such as poor stability,inability to enter cells autonomously,low translation efficiency,and immune stimulation activity.With a deepening understanding of m RNA structure and continuous progress in m RNA synthesis and modification-related technologies,optimization of the cap structure,5′-and 3′-untranslated regions,open reading frame,and poly(A)tail have been implemented to enhance m RNA stability,increase its expression levels in vivo,and reduce immune stimulation.Efficient m RNA delivery into target cells to enable high-level translation has always been a major problem in m RNA therapy.Developing safe and efficient delivery vectors has been a central pursuit to solve the problem.Based on the source of their composition,m RNA delivery vectors can be divided into two categories:Non-viral and viral.Non-viral vectors include lipid nanoparticles,polymers,extracellular vesicles,and peptides.The most commonly used is the lipid nanoparticles.However,problems with this non-viral vector remain,such as cell toxicity and the inability to target specific tissues.Viruses are natural vehicles for nucleic acid delivery.Viral m RNAvectors include lentivirus vectors,adenovirus vectors,adeno-associated virus(AAV)vectors,and virus-like particles(VLPs).VLPs have many beneficial features as m RNA vectors,such as uniform morphology,the activity of entering target cells,having three interfaces for modification,biocompatibility,biodegradability,and scalable production.According to whether they have a lipid membrane,VLPs are classified as enveloped or non-enveloped.In this review,the recent progress of m RNA delivery by VLPs is summarized.Specifically,cowpea chlorotic mottle virus(CCMV)VLP

关 键 词：MRNA 递送系统 病毒样颗粒 疫苗 基因编辑 

分 类 号：Q789[生物学—分子生物学]