Circular RNAs emerge as precision therapeutics, translating into bioactive peptides for disease treatment

Initially considered splicing byproducts, circular RNAs (circRNAs) are now understood as crucial regulators of gene and protein expression. Their unique covalently closed-loop structure provides stability, distinguishing them from linear RNAs. A significant recent discovery is that a subset of circRNAs can be translated through cap-independent mechanisms to produce novel bioactive peptides or proteins. This expands the functional scope of RNA beyond traditional coding and non-coding roles, opening new avenues for RNA therapy where conventional approaches may fall short in targeting complex disease pathways.

This comprehensive review systematically summarizes recent advances in circRNA biology, with a particular focus on their emerging potential in diagnosis and treatment. The authors evaluate various therapeutic strategies, including those targeting circRNAs at both the RNA and protein levels, and explore the critical role of delivery systems that support circRNA-directed therapies. The discussion extends to how circRNA therapeutics may be integrated into precision medicine, highlighting current clinical progress and identifying key challenges for advancing these novel therapies toward clinical application.

The review highlights that circRNAs are now recognized as essential regulators of gene and protein expression, playing significant roles in various human diseases. A key finding is that a subset of circRNAs can be translated through cap-independent mechanisms to produce bioactive peptides or proteins, expanding their functional scope beyond non-coding roles. These translated peptides offer novel therapeutic targets and interventions. The authors detail the potential of circRNAs in both disease diagnosis and treatment, emphasizing their versatility. They also outline diverse therapeutic strategies: > Targeting circRNAs can occur at both the RNA level (e.g., modulating their expression or function) and the protein level (e.g., utilizing their translated peptides as therapeutic agents or targets). The review further discusses the critical importance of effective delivery systems to enable circRNA-directed therapies and their integration into precision medicine approaches. Current clinical progress, though nascent, indicates a promising future for this class of therapeutics.