Circular RNA vaccine in disease prevention and treatment

Abstract CircRNAs are a class of single-stranded RNAs with covalently linked head-to-tail topology. In the decades since its initial discovery, their biogenesis, regulation, and function have rapidly disclosed, permitting a better understanding and adoption of them as new tools for medical applications. With the development of biotechnology and molecular medicine, artificial circRNAs have been engineered as a novel class of vaccines for disease treatment and prevention. Unlike the linear mRNA vaccine which applications were limited by its instability, inefficiency, and innate immunogenicity, circRNA vaccine which incorporate internal ribosome entry sites (IRESs) and open reading frame (ORF) provides an improved approach to RNA-based vaccination with safety, stability, simplicity of manufacture, and scalability. However, circRNA vaccines are at an early stage, and their optimization, delivery and applications require further development and evaluation. In this review, we comprehensively describe circRNA vaccine, including their history and superiority. We also summarize and discuss the current methodological research for circRNA vaccine preparation, including their design, synthesis, and purification. Finally, we highlight the delivery options of circRNA vaccine and its potential applications in diseases treatment and prevention. Considering their unique high stability, low immunogenicity, protein/peptide-coding capacity and special closed-loop construction, circRNA vaccine, and circRNA-based therapeutic platforms may have superior application prospects in a broad range of diseases.