Advancesand Challengesin Nanodelivery Systems forRNA Vaccines

Abstract RNA vaccines have become a transformative technology in infectious disease prevention and cancer treatment, thanks to their rapid development, high immunogenicity, and scalability in production. However, the clinical application of RNA vaccines faces significant challenges, including the inherent instability and susceptibility to degradation of naked RNA, its poor permeability across cell membranes, and the potential for nonspecific immune responses following systemic administration. Nanodelivery systems are key to addressing these challenges; by providing physical protection, enabling targeted delivery, promoting cellular uptake, and facilitating escape from endosomes, they significantly enhance the efficacy and safety of RNA vaccines. This review provides a comprehensive overview of the latest advances in nanodelivery systems for RNA vaccines, focusing on the characteristics of three distinct types of RNA vaccines─linear mRNA, self-amplifying RNA, and circular RNA─as well as the applications of lipid nanoparticles, polymeric nanoparticles, virus-like particles, and other emerging nanocarriers in enhancing RNA stability, boosting immunogenicity, and enabling precise targeting. Furthermore, this study will examine the key challenges in this field, including vector biosafety, large-scale production, cost-effectiveness, and storage and transportation, and will also outline future research directions and prospects for clinical translation.