Hou Xiaowen, Shi Jinjun, Xiao Yuling
Department of Cardiology, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
Center for Nanomedicine and Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Nano Res. 2024 Oct;17(10):9015-9030. doi: 10.1007/s12274-024-6978-6. Epub 2024 Sep 3.
Messenger RNA (mRNA) is a type of RNA that carries genetic information from DNA to the ribosome, where it is translated into proteins. mRNA has emerged as a powerful platform for development of new types of medicine, especially after the clinical approval of COVID-19 mRNA vaccines. Chemical modification and nanoparticle delivery have contributed to this success significantly by improving mRNA stability, reducing its immunogenicity, protecting it from enzymatic degradation, and enhancing cellular uptake and endosomal escape. Recently, substantial progresses have been made in new modification chemistries, sequence design, and structural engineering to generate more stable and efficient next-generation mRNAs. These innovations could further facilitate the clinical translation of mRNA therapies and vaccines. Given that numerous review articles have been published on mRNA nanoparticle delivery and biomedical applications over the last few years, we herein focus on overviewing recent advances in mRNA chemical modification, mRNA sequence optimization, and mRNA engineering (e.g., circular RNA and multitailed mRNA), with the aim of providing new perspectives on the development of more effective and safer mRNA medicines.
信使核糖核酸（mRNA）是一种将遗传信息从DNA携带至核糖体的核糖核酸，在核糖体处它被翻译为蛋白质。mRNA已成为新型药物开发的强大平台，尤其是在COVID-19 mRNA疫苗获得临床批准之后。化学修饰和纳米颗粒递送通过提高mRNA稳定性、降低其免疫原性、保护其免受酶降解以及增强细胞摄取和内体逃逸，为这一成功做出了重大贡献。最近，在新的修饰化学、序列设计和结构工程方面取得了实质性进展，以生成更稳定、更高效的下一代mRNA。这些创新可以进一步促进mRNA疗法和疫苗的临床转化。鉴于在过去几年中已经发表了大量关于mRNA纳米颗粒递送和生物医学应用的综述文章，我们在此重点概述mRNA化学修饰、mRNA序列优化和mRNA工程（如环状RNA和多尾mRNA）的最新进展，旨在为开发更有效、更安全的mRNA药物提供新的视角。
