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.
信使RNA（mRNA）药物在多种疾病的预防和治疗中展现了巨大的应用价值。最大程度提高mRNA的稳定性和翻译效率，保证mRNA免受核酸酶的降解并靶向特定组织和细胞是临床转化的要求。通过修饰核苷酸降低mRNA免疫原性，密码子优化增加mRNA翻译效率，5´帽结构和3´多聚腺苷酸尾结构增加mRNA稳定性，以及添加5´和3´非翻译区功能调控mRNA稳定性和翻译效率。通过纳米粒递送系统保护mRNA不被核酸酶降解，增加mRNA血液循环，并帮助mRNA进入细胞质发挥治疗和预防作用。本文综述了mRNA药物的制剂工程技术进展，讨论了提高mRNA稳定性和翻译效率的方法及设计原理，总结了具有产业转换潜力的mRNA递送系统的设计要求及其临床应用，并展望了mRNA药物未来可能的研究方向，以满足实现个性化精准医疗的需求。.
Keywords: Chemical modification; Drug delivery system; Messenger RNA; Nanodrug delivery system; Nucleic acid; RNA targeting; Review.