Artificial circular RNA sponges engineered in vitro efficiently sequestered microRNA-122 and inhibited Hepatitis C Virus protein production in a cell culture system.
Engineered circular RNAs can function as stable microRNA sponges, providing a proof-of-principle for their potential use in molecular medicine by successfully inhibiting HCV viral protein production.
Circular RNAs (circRNAs) were recently described as a novel class of cellular RNAs. Two circRNAs were reported to function as molecular sponges, sequestering specific microRNAs, thereby de-repressing target mRNAs. Due to their elevated stability in comparison to linear RNA, circRNAs may be an interesting tool in molecular medicine and biology. In this study, we provide a proof-of-principle that circRNAs can be engineered as microRNA sponges. As a model system, we used the Hepatitis C Virus (HCV), which requires cellular microRNA-122 for its life cycle. We produced artificial circRNA sponges in vitro that efficiently sequester microRNA-122, thereby inhibiting viral protein production in an HCV cell culture system. These circRNAs are more stable than their linear counterparts, and localize both to the cytoplasm and to the nucleus, opening up a wide range of potential applications.
Jost et al. (Wed,) conducted a other in Hepatitis C Virus (HCV). Artificial circular RNA sponges vs. Linear RNA counterparts was evaluated on Viral protein production. Artificial circular RNA sponges engineered in vitro efficiently sequestered microRNA-122 and inhibited Hepatitis C Virus protein production in a cell culture system.