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自我扩增mRNA疫苗:作用模式、设计、开发与优化

Self-amplifying mRNA vaccines: Mode of action, design, development and optimization.

作者信息

Pourseif Mohammad M, Masoudi-Sobhanzadeh Yosef, Azari Erfan, Parvizpour Sepideh, Barar Jaleh, Ansari Rais, Omidi Yadollah

机构信息

Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran; Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran; Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Drug Discov Today. 2022 Nov;27(11):103341. doi: 10.1016/j.drudis.2022.103341. Epub 2022 Aug 18.

DOI:10.1016/j.drudis.2022.103341
PMID:35988718
Abstract

The mRNA-based vaccines are quality-by-design (QbD) immunotherapies that provide safe, tunable, scalable, streamlined and potent treatment possibilities against different types of diseases. The self-amplifying mRNA (saRNA) vaccines, as a highly advantageous class of mRNA vaccines, are inspired by the intracellular self-multiplication nature of some positive-sense RNA viruses. Such vaccine platforms provide a relatively increased expression level of vaccine antigen(s) together with self-adjuvanticity properties. Lined with the QbD saRNA vaccines, essential optimizations improve the stability, safety, and immunogenicity of the vaccine constructs. Here, we elaborate on the concepts and mode-of-action of mRNA and saRNA vaccines, articulate the potential limitations or technical bottlenecks, and explain possible solutions or optimization methods in the process of their design and development.

摘要

基于信使核糖核酸(mRNA)的疫苗是质量源于设计(QbD)的免疫疗法,可为针对不同类型疾病提供安全、可调节、可扩展、简化且有效的治疗可能性。自我扩增mRNA(saRNA)疫苗作为一类极具优势的mRNA疫苗,其灵感来源于某些正链RNA病毒的细胞内自我增殖特性。此类疫苗平台可使疫苗抗原的表达水平相对提高,并具有自我佐剂特性。对于符合QbD的saRNA疫苗,关键的优化可提高疫苗构建体的稳定性、安全性和免疫原性。在此,我们详细阐述mRNA和saRNA疫苗的概念及作用方式,阐明其潜在局限性或技术瓶颈,并解释在其设计和开发过程中可能的解决方案或优化方法。

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