Principles, Optimization, Applications, and Future Prospects of mRNA Vaccine Technology

mRNA vaccines have emerged as a promising platform in vaccinology, enabling rapid and flexible antigen design. By delivering mRNA encoding target antigens, they allow in situ protein expression and induction of adaptive immune responses. Advances in sequence optimization, structural engineering, and delivery systems—particularly lipid nanoparticles (LNPs)—have improved mRNA stability, translational efficiency, and immunogenic performance in preclinical and clinical studies. Beyond infectious diseases, mRNA-based approaches are being explored in cancer immunotherapy, autoimmune disease modulation, and personalized medicine. Emerging platforms, including self-amplifying RNA and circular RNA, expand their potential applications. Despite these advances, challenges remain, such as the durability of immune responses, inter-individual variability, delivery specificity, and cold-chain requirements. Ongoing efforts are focused on improving these aspects through optimized delivery systems, novel administration routes, and the integration of artificial intelligence for sequence and formulation design. Notably, this review provides updated coverage of sequence design, manufacturing processes, delivery mechanisms, clinical applications, challenges, and future directions, with particular emphasis on recent advances in bacterial and parasitic mRNA vaccines and the AI-empowered closed-loop design of mRNA vaccines. Overall, mRNA technology represents a rapidly evolving and versatile platform with significant potential for future therapeutic development.