mRNA疫苗递送技术研究进展

Advances in mRNA Vaccine Delivery Technology

mRNA疫苗是利用编码特定抗原的mRNA在宿主细胞中表达特定抗原蛋白进而激活机体免疫系统、激活效应B细胞来产生特异性抗体或激活效应T细胞来发挥杀伤作用,最终达到预防或治疗疾病目的的一类核酸疫苗。mRNA疫苗具有生产周期短、免疫原性强、安全性高等优势,是近年来疫苗领域的研究热点。但mRNA极易被核酸酶降解导致的不稳定性和低递送效率严重限制了它的应用。为了保护mRNA免受核酸酶降解,提高mRNA疫苗的递送效率,促进mRNA疫苗的研究和临床应用,科学家们已经开发了一系列的mRNA疫苗递送技术。文章将对基于物理途径、脂质、聚合物、蛋白质及无机纳米颗粒的5大类递送技术及其应用进行综述,以期为mRNA疫苗的高效递送提供新思路和新方法。

mRNA vaccine is a kind of nucleic acid vaccine that uses mRNA encoding specific antigen to express specific antigen protein in host cells to activate the immune system of the body,activate effector B cells to produce specific antibodies or activate effector T cells to play a killing role,and finally achieve the purpose of preventing or treating diseases.mRNA vaccine has the advantages of short production cycle,strong immunogenicity and high safety,and has become a research hotspot in vaccine field in recent years.However,the instability and low delivery efficiency caused by the easy nuclease degradation of mRNA severely limit its application.In order to protect mRNA from nuclease degradation and improve the delivery efficiency of mRNA vaccine,and promote the research and clinical application of mRNA vaccine,scientists have developed a series of mRNA vaccine delivery technologies.mRNA delivery technologies can be roughly divided into five categories:The delivery technologies based on physical path,the delivery technologies based on lipid,the delivery technologies based on polymer,the delivery technologies based on protein,and the delivery technologies based on inorganic nanoparticle.The delivery technologies based on physical path include electroporation,gene gun,microneedle and other technologies.The delivery technologies based on lipid include liposome,cationic nanoemulsion,lipid nanoparticle,lipopolyplex and other technologies.The delivery technologies based on polymer mostly use polyethyleneimine,polyβ-amino ester,poly-amidoamine to deliver mRNA.The delivery technologies based on protein deliver mRNA with protamine,viruslike particle,cell-penetrating peptide and other proteins.The delivery technologies based on inorganic nanoparticle can deliver mRNA by gold nanoparticle,silica nanoparticle,calcium phosphate nanoparticle and other nanoparticles.In this paper,five types of delivery technologies based on physical path,lipid,polymer,protein,inorganic nanoparticle and their applications will be reviewed in order to provide new ideas and new methods for efficient delivery of mRNA vaccines.