信使核糖核酸(mRNA)疫苗及其递送系统的最新进展

IF 3.1 Q2 PHARMACOLOGY & PHARMACY Clinical Pharmacology : Advances and Applications Pub Date : 2023-01-01 DOI:10.2147/CPAA.S418314
Wubetu Yihunie, Getinet Nibret, Yibeltal Aschale
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摘要

信使核糖核酸(mRNA)在1961年被发现是将遗传信息从DNA传递到核糖体以合成蛋白质的中介。BNT162b2和mRNA-1273两种新冠病毒mRNA疫苗获得紧急使用授权,是疫苗发展史上的一项重大成就。由于mRNA疫苗是通过体外转录(IVT)过程在无细胞环境中产生的,因此是无风险的。此外,对mRNA分子的化学修饰,如帽结构和核苷的改变,已被证明是克服免疫原性问题、实现持续稳定性和在体内实现有效、准确的蛋白质生产的关键。几种疫苗递送策略(包括鱼精蛋白、脂质纳米颗粒(LNPs)、聚合物、纳米乳液和基于细胞的给药)也被优化,以装载和运输RNA到细胞质溶胶中。LNPs由阳离子或ph依赖性电离脂质层、聚乙二醇(PEG)组分、磷脂和胆固醇组成,是递送mRNA疫苗的最先进系统。此外,对组成LNPs的四种成分进行修饰可以提高疫苗的有效性并减少副作用。此外,生物可降解脂类的引入改善了LNP的生物相容性。此外,基于mrna的疗法有望成为各种难治性疾病的有效治疗方法,包括传染病、代谢遗传疾病、癌症、心脑血管疾病。因此,本综述旨在为科学界提供有关mRNA疫苗及其递送系统的最新信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Recent Advances in Messenger Ribonucleic Acid (mRNA) Vaccines and Their Delivery Systems: A Review.

Messenger ribonucleic acid (mRNA) was found as the intermediary that transfers genetic information from DNA to ribosomes for protein synthesis in 1961. The emergency use authorization of the two covid-19 mRNA vaccines, BNT162b2 and mRNA-1273, is a significant achievement in the history of vaccine development. Because they are generated in a cell-free environment using the in vitro transcription (IVT) process, mRNA vaccines are risk-free. Moreover, chemical modifications to the mRNA molecule, such as cap structures and changed nucleosides, have proved critical in overcoming immunogenicity concerns, achieving sustained stability, and achieving effective, accurate protein production in vivo. Several vaccine delivery strategies (including protamine, lipid nanoparticles (LNPs), polymers, nanoemulsions, and cell-based administration) were also optimized to load and transport RNA into the cytosol. LNPs, which are composed of a cationic or a pH-dependent ionizable lipid layer, a polyethylene glycol (PEG) component, phospholipids, and cholesterol, are the most advanced systems for delivering mRNA vaccines. Moreover, modifications of the four components that make up the LNPs showed to increase vaccine effectiveness and reduce side effects. Furthermore, the introduction of biodegradable lipids improved LNP biocompatibility. Furthermore, mRNA-based therapies are expected to be effective treatments for a variety of refractory conditions, including infectious diseases, metabolic genetic diseases, cancer, cardiovascular and cerebrovascular diseases. Therefore, the present review aims to provide the scientific community with up-to-date information on mRNA vaccines and their delivery systems.

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来源期刊
CiteScore
4.60
自引率
0.00%
发文量
14
审稿时长
16 weeks
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