Abstract
Circular RNA (circRNA) is emerging as a next-generation therapeutic platform capable of sustaining protein expression over extended periods, offering a promising alternative to conventional therapies and messenger RNA (mRNA)-based interventions. Its covalently closed structure provides exceptional stability and resistance to degradation, enabling prolonged protein production. In contrast, mRNA, while enabling transient cytoplasmic expression without altering the genome, is inherently unstable and rapidly cleared, limiting its therapeutic durability. In this study, we directly compared circRNA and mRNA under identical experimental conditions across diverse cellular microenvironments. CircRNA demonstrated superior expression efficiency and kinetics, achieving higher total protein output, prolonged expression, and delayed clearance. The magnitude of these advantages was cell type–dependent: the highest benefit was observed in endothelial microenvironments, followed by tumor microenvironments, while in highly phagocytic immune microenvironments, both circRNA and mRNA were rapidly cleared, minimizing any advantage, indicating that tissue-specific factors critically influence circRNA performance. These results show that while circRNA generally outperforms mRNA in protein expression and stability, its therapeutic benefits vary with cellular context. By benchmarking circRNA against mRNA across multiple microenvironments, this study provides a framework for guiding the rational design of RNA-based therapeutics. Overall, circRNA represents a promising platform that combines enhanced stability, reduced immunogenicity, and sustained protein production, advancing the development of next-generation treatments for chronic diseases.
Presenters
Nelly AndrewsStudent, RFC: ITE430714KI0, Instituto Tecnológico y de Estudios Superiores de Monterrey, Mexico
Details
Presentation Type
Theme
Interdisciplinary Health Sciences
KEYWORDS
CircRNA, MRNA, Delivery Systems, Biotechnology, RNA Therapy
