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

IF 4.5 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Molecular Pharmaceutics Pub Date : 2024-11-27 DOI:10.1021/acs.molpharmaceut.4c00863

Lifeng Xu, Chao Li, Rui Liao, Qin Xiao, Xiaoran Wang, Zhuo Zhao, Weijun Zhang, Xiaoyan Ding, Yuxue Cao, Larry Cai, Joseph Rosenecker, Shan Guan, Jie Tang

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引用次数: 0

Abstract

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.

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从序列到系统：通过尖端技术提高 IVT mRNA 疫苗的有效性。

COVID-19 大流行凸显了体外转录 (IVT) mRNA 疫苗的潜力，其功效、安全性、成本效益和快速制造已得到证实。目前，许多体外转录 mRNA 疫苗正在针对一系列目标进行临床试验，包括传染病、癌症和遗传性疾病。尽管 IVT mRNA 疫苗前景广阔，但也面临着一些障碍，如表达水平有限、肝脏以外的非特异性靶向、快速降解和意外免疫激活等。要充分发挥 IVT mRNA 疫苗的治疗潜力，促进全球健康发展，克服这些挑战至关重要。本综述全面概述了 IVT mRNA 分子和递送系统的最新研究进展和优化策略，包括人工智能（AI）模型和深度学习技术在 IVT mRNA 结构优化和 mRNA 递送配方设计中的应用。我们还讨论了脂质纳米颗粒（LNPs）、聚合物和外泌体等递送平台的最新发展，这些平台旨在解决与 IVT mRNA 保护、细胞吸收和靶向递送相关的挑战。最后，我们对改进 IVT mRNA 疫苗的未来方向提出了见解，希望能推动 IVT mRNA 疫苗研究与开发的进一步发展。

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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来源期刊

Molecular Pharmaceutics 医学-药学

CiteScore

8.00

自引率

6.10%

发文量

391

审稿时长

2 months

期刊介绍： Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development. Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.