mRNA疫苗及其基于聚合物的递送系统研究进展<sup>*</sup>

doi:10.13523/j.cb.2211043

中国生物工程杂志

2023, Vol. 43

Issue (5): 55-68 DOI: 10.13523/j.cb.2211043

综述

mRNA疫苗及其基于聚合物的递送系统研究进展^*

张亚茹¹,王慧梅¹,迟永杰²,高媛¹,赵颖¹,暴佳欣³,张竞²,王连艳^2,^**(

)

1 东北林业大学化学化工与资源利用学院哈尔滨 150040
2 中国科学院过程工程研究所生化工程国家重点实验室北京 100190
3 黑龙江中医药大学药学院哈尔滨 150040

Research Progress of mRNA Vaccines and Polymer-based Delivery Systems

ZHANG Ya-ru¹,WANG Hui-mei¹,CHI Yon-jie²,GAO Yuan¹,ZHAO Ying¹,BAO Jia-xin³,ZHANG Jin²,WANG Lian-yan^2,^**(

)

1 College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University,Haerbin 150040, China
2 State Key Laboratory, Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China
3 College of Pharmacy, Heilongjiang University of Chinese Medicine, Haerbin 150040, China

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摘要：

2019年,全球暴发了严重急性呼吸综合征冠状病毒2型(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)疫情。由SARS-CoV-2引起的传染病(Corona Virus Disease 2019,COVID-19)具有极强的传染性及较高的病死率,对人类健康及经济发展造成了极大伤害。疫苗接种是预防和控制SARS-CoV-2传播的主要途径。信使RNA(mRNA)疫苗因具有制备简单、生产周期短、细胞毒性较小等优点而备受关注;最重要的是,mRNA容易实现量产,是应对突发疫情的重要手段之一。在此将对mRNA疫苗及其作用机制、递送载体以及给药方式等进行综述,旨在为mRNA疫苗研发工作提供参考。

关键词： mRNA疫苗; 作用机制; 递送系统; 给药方式; COVID-19 mRNA疫苗

Abstract:

There was a global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019. The pandemic of corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 shows high infectivity and fatality rate, which has caused a great burden on human health and economic development. Vaccination is an important way to prevent and control the prevalence and spread of SARS-CoV-2. A lot of vaccines are developed and applied to prevent and control it, such as inactivated viruses vaccines, recombinant subunit protein vaccines, adenovirus vector vaccines and messenger RNA (mRNA) vaccines. The mRNA is a new drug model, which can use the body’s own translation system to express proteins with different functions. Therefore, it can be used in the treatment of many diseases, which is also considered to be a substitute for DNA and recombinant protein mediated therapy. With mRNA synthesis, purification and modification in vitro, scientists find that the mRNA is easy to be degraded due to its instability, which leads to lower transfection efficiency. Therefore, it is necessary to fabricate and develop a suitable delivery system for improving its stability and translation efficiency. The successful delivery system makes mRNA drugs attract more and more attention in cancer treatment, infectious disease prevention, protein replacement therapy and gene editing. Until now, many delivery carriers have been designed and evaluated including dendrimers, liposome, nano-emulsions and polymer nanoparticles. In addition, mRNA vaccines show such excellent characteristics as simple preparation, short development and production cycle and little cytotoxicity. Most importantly, mRNA vaccines are easy to scale up. All these advantages result in mRNA vaccines’ suitablity to deal with infection outbreaks. Here we will review the mRNA vaccine, the mechanism of action, the delivery vector and the administration ways of the mRNA vaccine, in order to provide reference for the mRNA vaccine research and development.

Key words: mRNA vaccines Action mechanism Delivery system Administration method COVID-19 mRNA vaccine

收稿日期: 2022-11-22 出版日期: 2023-06-01

ZTFLH:

Q819

基金资助: ^*国家自然科学基金面上项目(8197362);北京市自然科学基金-海淀原始创新联合基金重点研究项目(L202001);北京市自然科学基金-海淀原始创新联合基金前沿项目(L202039)

通讯作者: **电子信箱: wanglianyan@ipe.ac.cn

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	张亚茹
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引用本文:

张亚茹, 王慧梅, 迟永杰, 高媛, 赵颖, 暴佳欣, 张竞, 王连艳. mRNA疫苗及其基于聚合物的递送系统研究进展^*[J]. 中国生物工程杂志, 2023, 43(5): 55-68.

ZHANG Ya-ru, WANG Hui-mei, CHI Yon-jie, GAO Yuan, ZHAO Ying, BAO Jia-xin, ZHANG Jin, WANG Lian-yan. Research Progress of mRNA Vaccines and Polymer-based Delivery Systems. China Biotechnology, 2023, 43(5): 55-68.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2211043 或 https://manu60.magtech.com.cn/biotech/CN/Y2023/V43/I5/55

图1 mRNA产品所处临床阶段分布

图2 mRNA疫苗作用机制图

图3 用于药物和疫苗递送的纳米载体

表1 脂质纳米递送系统和聚合物纳米载体的比较

图4 不同聚合物基纳米制剂的近似尺寸及其与生物分子或生物体尺寸的比较[39]

图5 树状大分子结构示意图

图6 聚合物胶束负载mRNA过程示意图

图7 负载mRNA聚合物纳米球和纳米囊的结构示意图

表2 辉瑞-生物科技(BNT162b2)和Moderna (mRNA-1273)疫苗的主要特征

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