From Sequence to System: Enhancing IVT mRNA Vaccine Effectiveness through Cutting-Edge Technologies

被引：0
作者：
Xu, Lifeng [1 ]
Li, Chao [1 ]
Liao, Rui [1 ]
Xiao, Qin [1 ]
Wang, Xiaoran [2 ]
Zhao, Zhuo [1 ]
Zhang, Weijun [1 ]
Ding, Xiaoyan [3 ]
Cao, Yuxue [4 ]
Cai, Larry [4 ]
Rosenecker, Joseph [3 ]
Guan, Shan [1 ]
Tang, Jie [4 ]
机构：
[1] Third Mil Med Univ, Natl Engn Res Ctr Immunol Prod, Chongqing 400038, Peoples R China
[2] Xinjiang Med Univ, Affiliated Hosp 1, Dept Pharm, Urumqi 830000, Peoples R China
[3] Ludwig Maximilians Univ Munchen, Dept Pediat, D-80337 Munich, Germany
[4] Monash Univ, Monash Inst Pharmaceut Sci, Drug Delivery Disposit & Dynam, Parkville, Vic 3052, Australia
来源：
MOLECULAR PHARMACEUTICS | 2024年 / 22卷 / 01期
基金：
中国国家自然科学基金; 英国医学研究理事会;
关键词：
mRNA vaccines; sequence optimization; deliverysystems; lipid nanoparticles; drug delivery; artificial intelligence; IN-VITRO; TRANSLATION INITIATION; DECAY-RATES; PROTEIN; DELIVERY; NANOPARTICLES; RECOGNITION; EXPRESSION; PROGRESS; PSEUDOURIDINE;
D O I：
10.1021/acs.molpharmaceut.4c00863
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
The COVID-19 pandemic has spotlighted the potential of in vitro transcribed (IVT) mRNA vaccines with their demonstrated efficacy, safety, cost-effectiveness, and rapid manufacturing. Numerous IVT mRNA vaccines are now under clinical trials for a range of targets, including infectious diseases, cancers, and genetic disorders. Despite their promise, IVT mRNA vaccines face hurdles such as limited expression levels, nonspecific targeting beyond the liver, rapid degradation, and unintended immune activation. Overcoming these challenges is crucial to harnessing the full therapeutic potential of IVT mRNA vaccines for global health advancement. This review provides a comprehensive overview of the latest research progress and optimization strategies for IVT mRNA molecules and delivery systems, including the application of artificial intelligence (AI) models and deep learning techniques for IVT mRNA structure optimization and mRNA delivery formulation design. We also discuss recent development of the delivery platforms, such as lipid nanoparticles (LNPs), polymers, and exosomes, which aim to address challenges related to IVT mRNA protection, cellular uptake, and targeted delivery. Lastly, we offer insights into future directions for improving IVT mRNA vaccines, with the hope to spur further progress in IVT mRNA vaccine research and development.
引用
收藏
页码：81 / 102
页数：22
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