Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules generated through canonical or noncanonical

backsplicing events and have garnered attention as innovative therapeutic platforms owing to their exceptional 

stability and low immunogenicity. Here, we highlighted the diverse functions of circRNA, including microRNA sequestration,

scaffolding of RNA-binding proteins, and cap-independent protein translation mediated by internal ribosome entry 

sites (IRESs) or N6-methyladenosine (m6A), all of which contribute to disease modulation and sustained protein expression.

Recent advances in circularization strategies have enabled the production of high-purity synthetic circRNAs with 

precisely controlled translational efficiency and reduced immunogenicity. We highlighted a variety of preclinical studies 

which demonstrated the robust and durable efficacy of circmRNA vaccines, protein replacement therapies, circular interfering

RNAs (ciRNAs) for gene silencing, and circular guide RNAs (cgRNAs) for genome editing and circRNA aptamerbased

PKR inhibition. Nonetheless, challenges persist in standardizing large-scale manufacturing processes, preventing 

off-target effects, and comprehensively evaluating immunological responses and safety profiles. This review proposes 

a future perspective incorporating automated purification, high-throughput screening, and artificial intelligence-driven 

design to accelerate the clinical application of circRNA-based therapeutics.