mRNA疫苗的研究及应用进展

doi:10.19586/j.2095-2341.2023.0015

生物技术进展 ›› 2023, Vol. 13 ›› Issue (4): 492-498.DOI: 10.19586/j.2095-2341.2023.0015

• 进展评述 • 上一篇

mRNA疫苗的研究及应用进展

蔚丹¹(), 马云龙¹, 万方¹(), 武建强²()

^1.内蒙古农业大学生命科学学院，呼和浩特 010010
^2.内蒙古医科大学基础医学院，呼和浩特 010107

收稿日期:2023-02-13 接受日期:2023-03-31 出版日期:2023-07-25 发布日期:2023-08-03
通讯作者: 万方,武建强
作者简介:蔚丹E-mail:1808367024@qq.com；

Advances on Research and Application of mRNA Vaccines

Dan YU¹(), Yunlong MA¹, Fang WAN¹(), Jianqiang WU²()

^1.Faculty of Life Science，Inner Mongolia Agricultural University，Huhehot 010010，China
^2.College of Basic Medicine，Inner Mongolia Medical University，Huhehot 010107，China

Received:2023-02-13 Accepted:2023-03-31 Online:2023-07-25 Published:2023-08-03
Contact: Fang WAN,Jianqiang WU

摘要/Abstract

摘要：

与传统疫苗相比，mRNA疫苗具有高效、安全、低成本等优点，但它的应用一直受到体内传递不稳定、翻译效率较低等技术问题的限制。新型冠状病毒的流行及其疫苗的研发加速了mRNA疫苗的研发和批准，特别是在mRNA结构修饰及脂质纳米颗粒构建等方面有了突破性进展，如使用优化后核苷、帽子结构的mRNA疫苗稳定性大大提高，替换低使用频率的密码子可提高其翻译效率等。目前常用的mRNA递送系统有脂质纳米颗粒、聚合物载体、类病毒载体等。综述了mRNA疫苗的发展历程、作用机制、修饰技术突破和递送系统方面的研究及应用进展，以期促进mRNA疫苗的深入研究及应用。

关键词: mRNA疫苗, 作用机制, 递送系统

Abstract:

Compared with traditional vaccines， mRNA vaccines have the advantages of high efficiency， safety and low cost， but its application has been limited by technical problems such as unstable in vivo delivery and low translation efficiency. The prevalence of SARS-CoV-2 virus and their vaccine development have accelerated the development and approval of mRNA vaccines， especially breakthroughs in mRNA structural modification and construction of lipid nanoparticles， for example， the stability of mRNA vaccines using optimized nucleoside and cap structures is greatly improved， and the replacement of codons with low frequency of use can improve their translation efficiency. The commonly used mRNA delivery systems are lipid nanoparticles， polymer vectors， virus-like vectors， etc. The research and application progress of development history， mechanism of action， technological breakthroughs in modification， and delivery systems of mRNA vaccines were reviewed in order to promote the in-depth research and application of mRNA vaccines.

Key words: mRNA vaccine, mechanism of action, delivery system

中图分类号:

Q812

蔚丹, 马云龙, 万方, 武建强. mRNA疫苗的研究及应用进展[J]. 生物技术进展, 2023, 13(4): 492-498.

Dan YU, Yunlong MA, Fang WAN, Jianqiang WU. Advances on Research and Application of mRNA Vaccines[J]. Current Biotechnology, 2023, 13(4): 492-498.

图/表 3

图1 mRNA疫苗引发免疫反应的过程图注：①注射的mRNA疫苗被抗原呈递细胞或肿瘤细胞内吞。②mRNA脱离内体进入细胞质后，被核糖体翻译成蛋白质，翻译的抗原蛋白可用于刺激免疫系统。③经过翻译的抗原蛋白被蛋白酶体复合物分解成更小的片段，这些片段通过组织相容性复合物(major histocompatibility complex，MHC) Ⅰ类蛋白形成复合物，在细胞表面递呈给细胞毒性T细胞。④活化的细胞毒性T细胞通过分泌细胞因子，如穿孔素、颗粒酶等，杀死感染细胞。⑤mRNA也可与肿瘤细胞膜融合后进入细胞，表达为蛋白质，细胞裂解后释放出大量抗原。⑥分泌的抗原可以被APC摄取，在内体中降解，并与MHC Ⅱ类蛋白形成复合物pMHC，在细胞表面呈现给辅助性T细胞。⑦辅助性T细胞识别pMHC并通过刺激B细胞产生特异性的中和抗体，通过炎症细胞因子激活吞噬细胞，如巨噬细胞等，促进病原体的清除。

Fig. 1 Process of mRNA vaccine?induced immune response

表1 密码子使用频率

Table 1 Codon usage frequency

密码子	频率/10³	密码子	频率/10³	密码子	频率/10³
UUU F	17.6	UCU S	15.2	UAU Y	12.2
UUC F	20.3	UCC S	17.7	UAC Y	15.3
UUA L	7.7	UCA S	12.2	UAA *	0.8
UUG L	12.9	UCG S	4.4	UAG *	0.8
CUU L	13.2	CCU P	17.5	CAU H	10.9
CUC L	19.6	CCC P	19.8	CAC H	15.1
CUA L	7.2	CCA P	16.9	CAA Q	12.3
CUG L	39.6	CCG P	6.9	CAG Q	34.2
AUU I	16.0	ACU T	13.1	AAU N	17.0
AUC I	20.8	ACC T	18.9	AAC N	19.1
AUA I	7.5	ACA T	15.1	AAA K	24.4
AUG M	22.0	ACG T	6.1	AAG K	31.9
GUU V	11.0	GCU A	18.4	GAU D	21.8
GUC V	14.5	GCC A	27.7	GAC D	25.1
GUA V	7.1	GCA A	15.8	GAA E	29.0
GUG V	28.1	GCG A	7.4	GAG E	39.6

图2 核苷酸的基本结构与化学修饰

Fig. 2 Basic structure and chemical modification of nucleotides

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mRNA疫苗的研究及应用进展

Advances on Research and Application of mRNA Vaccines

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