Self-Amplifying RNA: Advantages and Challenges of a Versatile Platform for Vaccine Development

Self-amplifying RNA is synthetic nucleic acid engineered to replicate within cells without generating viral particles. Derived from alphavirus genomes, saRNA retains the non-structural elements essential for replication while replacing the structural elements with an antigen of interest. By enabling efficient intracellular amplification, saRNA offers a promising alternative to conventional mRNA vaccines, enhancing antigen expression while requiring lower doses. However, this advantage comes with challenges. In this review, we highlight the key limitations of saRNA technology and explore potential strategies to overcome them. By identifying these challenges, we aim to provide insights that can guide the future design of saRNA-based therapeutics, extending their potential beyond vaccine applications.