The advent of clinical self-amplifying RNA vaccines.

Self-amplifying RNA (saRNA) technology is an emerging platform for vaccine development, offering significant advantages over conventional mRNA vaccines. By enabling intracellular amplification of RNA, saRNA facilitates robust antigen expression at lower doses, thereby enhancing both immunogenicity and cost-effectiveness. This review examines the latest advancements in saRNA vaccine development, highlighting its applications in combating infectious diseases, including viral pathogens such as SARS-CoV-2, influenza, and emerging zoonotic threats. We discuss the design and optimization of saRNA vectors to maximize antigen expression while minimizing adverse immune responses. Recent studies demonstrating the safety, efficacy, and scalability of saRNA-based vaccines in clinical settings are also discussed. We address challenges related to delivery systems, stability, and manufacturing, along with novel strategies being developed to mitigate these challenges. As the global demand for rapid, flexible, and scalable vaccine platforms grows, saRNA presents a promising solution with enhanced potency and durability. This review emphasizes the transformative potential of saRNA vaccines to shape the future of immunization strategies, particularly in response to pandemics and other global health threats.