Bai Chenghai, Wang Chen, Lu Yuan
Key Laboratory of Industrial Biocatalysis, Ministry of Education, Tsinghua University, Beijing, 100084, China.
Department of Chemical Engineering, Tsinghua University, Beijing, 100084, China.
Small. 2023 Nov;19(46):e2303713. doi: 10.1002/smll.202303713. Epub 2023 Jul 20.
mRNA therapy has shown great potential in infectious disease vaccines, cancer immunotherapy, protein replacement therapy, gene editing, and other fields due to its central role in all life processes. However, mRNA is challenging to pass through the cell membrane due to its significant negative charges and degradation from RNase, so the key to mRNA therapy is efficient packaging and delivery of it with appropriate vectors. Presently researchers have developed various vectors such as viruses and liposomes, but these conventional vectors are now difficult to meet the growing requirement like safety, efficiency, and targeting, so many novel delivery vectors with unique advantages have emerged recently. This review mainly introduces two categories of novel vectors: biomacromolecules and inorganic nanoparticles, as well as two novel methods of control and administration based on these novel vectors: controlled-release administration and non-invasive administration. These novel delivery strategies have the advantages of high safety, biocompatibility, versatility, intelligence, and targeting. This paper analyzes the challenges faced by the field of mRNA delivery in depth, and discusses how to use the characteristics of novel vectors and administrations to solve these problems.
由于信使核糖核酸（mRNA）在所有生命过程中发挥着核心作用，mRNA疗法在传染病疫苗、癌症免疫疗法、蛋白质替代疗法、基因编辑等领域展现出了巨大潜力。然而，mRNA因带有大量负电荷且易被核糖核酸酶（RNase）降解，难以穿过细胞膜，因此mRNA疗法的关键在于用合适的载体对其进行高效包装和递送。目前，研究人员已开发出多种载体，如病毒和脂质体，但这些传统载体如今难以满足安全性、效率和靶向性等日益增长的需求，因此最近出现了许多具有独特优势的新型递送载体。本综述主要介绍两类新型载体：生物大分子和无机纳米颗粒，以及基于这些新型载体的两种新型控制和给药方法：控释给药和非侵入性给药。这些新型递送策略具有高安全性、生物相容性、多功能性、智能性和靶向性等优点。本文深入分析了mRNA递送领域面临的挑战，并探讨了如何利用新型载体和给药方式的特性来解决这些问题。
