Huayuan Zhou, Dali Wei, Zhejie Chen, Hao Chen, Chuhuang Dong, Wei Yao, Jiawen Wang, Xueliang Liu, Yuqing Li, Yu Yang, Weihong Tan
As the central template for protein expression, messenger ribonucleic acid (mRNA) holds immense potential for novel therapeutic strategies. Over the past few decades, mRNA-based therapeutics have demonstrated remarkable efficacy in a range of applications, including epidemic vaccine, cancer vaccine, protein replacement therapy, cytokine therapy, cell therapy and gene editing. Due to the inherent instability of mRNA, the rational design of mRNA structure is the prerequisite for therapeutic utility while effective delivery systems are also essential for in vivo applications. This review focuses on the optimization of mRNA structure and highlights key delivery strategies. It also provides a comprehensive overview of the major applications of mRNA-based strategies. In addition, it highlights the persistent challenges in mRNA therapeutics, particularly in terms of stability, immunogenicity, delivery efficiency and safety. By examining recent advances in mRNA design, delivery and application, this review aims to support ongoing research and development in the field of mRNA-based therapeutics.