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中国生物工程杂志

China Biotechnology
China Biotechnology  2023, Vol. 43 Issue (5): 55-68    DOI: 10.13523/j.cb.2211043
    
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-yan2,**()
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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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 wordsmRNA vaccines      Action mechanism      Delivery system      Administration method      COVID-19 mRNA vaccine     
Received: 22 November 2022      Published: 01 June 2023
ZTFLH:  Q819  
Cite this article:

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.

URL:

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

Fig.1 Clinical stage distribution of mRNA products
Fig.2 Mechanism of action of mRNA vaccine
Fig.3 Nanocarriers commonly used for drug and vaccine delivery
脂质纳米递送系统 聚合物纳米载体
组装方式 由阳离子脂质材料与mRNA通过静电作用形成复合物 以阳离子聚合物为载体,与mRNA通过静电作用自组装形成聚电解质络合物
优缺点 优点:脂质体是球形囊泡,可以封装mRNA并抵抗核酸酶;脂质体与细胞膜相似,易于与受体细胞融合,转染效率高。
缺点:脂质体不稳定、易水解,在递送过程中容易渗漏
优点:聚合物纳米载体比表面积大、药代动力学稳定;结构易于修饰(如增加亲水或疏水基团),降低分子本身毒性或增强与细胞膜的作用,从而提高转染效率
代表性材料 三甲基氯化铵(DOTAP)、1,2-双十八烯氧基-3-甲基铵丙烷(DOTMA)、SM-102(已用于抗SARS-CoV-2的Moderna疫苗mRNA-1273)、ALC-0315(已用于辉瑞疫苗BNT162b2)等 聚氨基胺(PAA)、聚赖氨酸(PLL)、聚酰胺-胺(PAMAM)树状物、聚氨基酯(PBAEs)、聚乙烯亚胺(PEI)、聚乳酸-羟基乙酸共聚物(PLGA)等
Table 1 Comparison between lipid nano delivery system and polymer nano carrier
Fig.4 Approximate sizes of different polymer based nanoformulations and their comparison with biomolecules or biological sizes
Fig.5 Schematic diagram of dendrimer structure
Fig.6 Schematic diagram of polymer micelles loading mRNA
Fig.7 Structural schematic of mRNA loaded polymer nanospheres and nanocapsules
Pfizer-BioNTech 疫苗(BNT162b2) Moderna疫苗(mRNA-1273)
mRNA 编码SARS-CoV-2病毒刺突糖蛋白的modRNA
脂质纳米颗粒
合成编码SARS-CoV-2刺激性糖蛋白的mRNA
脂质纳米颗粒
递送系统
FDA授予EUA
剂量
注射次数
有效性
稳定性/储存

说明
2020年12月11日
0.3 mL,含30 μg疫苗
两剂,第一剂21~28天后注射第二剂
95%
-80~-60℃(6个月)
2~8℃(5天)
以冷冻悬浮液的形式提供
必须解冻,然后用1.8 mL无防腐剂无菌盐水溶液(0.9%,m/V)稀释
稀释后,疫苗需要储存在2~5℃,并在6 h内给药
2020年12月18日
0.5 mL,含100 μg疫苗
两剂,第一剂28天后注射第二剂
94.1%
-25~-15℃(6个月)
2~8℃(30天)
以冷冻悬浮液的形式提供
疫苗在给药前必须解冻

解冻后,疫苗需要储存在2~25℃,并在6 h内给药
Table 2 Key features of Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) vaccines
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