Abstract:As an emerging nucleic acid vaccine technology, mRNA vaccines have undergone rapid development and achieved commercial application since the COVID-19 pandemic. Owing to their flexible design, short development cycles, and ability to induce both humoral and cellular immune responses, this technology has become an important platform for infectious disease prevention and control as well as cancer immunotherapy. However, insufficient stability remains a critical bottleneck hindering the widespread application and industrial development of mRNA vaccines. The mRNA molecule itself is susceptible to degradation due to physical, chemical, and biological factors, while the lipid nanoparticle delivery system is prone to issues such as particle aggregation, increased particle size, structural changes in the lipid membrane, and mRNA leakage during storage, freeze-thaw cycles, and transportation, thereby compromising the immunogenicity and safety of the vaccine. This review comprehensively addresses the stability challenges of mRNA vaccines, examining key factors affecting their physical, chemical, and functional stability from multiple perspectives, including molecular structure, delivery systems, production processes, and storage conditions. Furthermore, it outlines future strategies for enhancing stability, with the aim of providing research insights for long-term stability studies and industrial development of mRNA vaccines.