CircRNA: Unlocking new frontiers in therapeutic and vaccine development

Circular RNAs (circRNAs), a newly identified class of RNA molecules with unique structural and functional features, represent an efficient platform for therapeutic and vaccine development. Their covalently closed-loop structure confers remarkable stability and resistance to exonuclease degradation. Furthermore, circRNAs can initiate cap-independent translation via internal ribosome entry sites (IRESs). These properties overcome several limitations of linear RNA molecules, including short half-life, instability, and stringent storage requirements of mRNA-based vaccines. Recently, the potential of circRNA as an innovative vaccine platform for combating infectious diseases and cancer has been demonstrated. These RNA-based vaccines can encode specific antigens and elicit robust immune responses. In addition, circRNAs play essential roles in gene regulation by acting as microRNA sponges and scaffolds for protein interactions, and they may also serve as potential diagnostic biomarkers. This review provides a comprehensive overview of circRNA biology, emphasizing their biogenesis, functional mechanisms, and translational potential. We also highlight the design, synthesis, delivery strategies, and immunological mechanisms of circRNA vaccines and review their application in cancer therapy and various infectious diseases.