mRNA 药物修饰与递送系统的研究进展。

Research progress in mRNA drug modification and delivery systems.

机构信息

Department of Medicine, Pritzker School of Molecular Engineering, The University of Chicago, Chicago 60637, USA.

The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Center for RNA Medicine, International Institutes of Medicine, Zhejiang University, Jinhua 322000, Zhejiang Province, China.

出版信息

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2023 Aug 25;52(4):439-450. doi: 10.3724/zdxbyxb-2023-0101.

Abstract

Messenger RNA (mRNA) has shown tremendous potential in disease prevention and therapy. The clinical application requires mRNA with enhanced stability and high translation efficiency, ensuring it not to be degraded by nucleases and targeting to specific tissues and cells. mRNA immunogenicity can be reduced by nucleotide modification, and translation efficiency can be enhanced by codon optimization. The 5´ capping structure and 3´ poly A increase mRNA stability, and the addition of 5' and 3' non-translational regions regulate mRNA translation initiation and protein production. Nanoparticle delivery system protects mRNA from degradation by ubiquitous nucleases, enhances mRNA concentration in circulation and assists it cytoplasmic entrance for the purpose of treatment and prevention. Here, we review the recent advances of mRNA technology, discuss the methods and principles to enhance mRNA stability and translation efficiency; summarize the requirements involved in designing mRNA delivery systems with the potential for industrial translation and biomedical application. Furthermore, we provide insights into future directions of mRNA therapeutics to meet the needs for personalized precision medicine.

摘要

信使 RNA(mRNA)在疾病预防和治疗方面显示出巨大的潜力。临床应用需要具有增强稳定性和高翻译效率的 mRNA,以确保其不被核酶降解,并靶向特定的组织和细胞。通过核苷酸修饰可以降低 mRNA 的免疫原性,通过密码子优化可以提高翻译效率。5´ 帽结构和 3´ 聚 A 增加了 mRNA 的稳定性,添加 5´ 和 3´ 非翻译区调节 mRNA 翻译起始和蛋白质产生。纳米颗粒递送系统可以保护 mRNA 免受普遍存在的核酶的降解,提高 mRNA 在循环中的浓度,并协助其进入细胞质,以达到治疗和预防的目的。在这里,我们回顾了 mRNA 技术的最新进展,讨论了增强 mRNA 稳定性和翻译效率的方法和原则;总结了具有工业转化和生物医学应用潜力的 mRNA 递送系统设计所涉及的要求。此外,我们还对 mRNA 治疗学的未来方向进行了探讨,以满足个性化精准医学的需求。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1df2/10495253/1001fd2d830f/1008-9292-2023-52-4-439-g001.jpg

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