2P-215 : Development of Dicer Substrate RNA Nanostructures for Efficient Gene Silencing

Small interfering RNAs (siRNAs) has great therapeutic potential for treating various diseases since they suppress target protein expression involved in pathogenesis with the known genetic sequence. Nevertheless, introducing RNA therapeutics to clinical applications requires improvement of potency and prolongation of therapeutic effect. By utilizing rolling circle transcription to synthesize clustered hairpin RNA, we aim to develop a sustained release system of siRNA to extend the duration of gene silencing. The RNA nanostructure in cytoplasm diffuses into nucleus by cell cycle dependent manner and effector protein Drosha cleaves the hairpin RNA to release the precursor of the dicer substrate RNA nanostructures. Our study provides a unique strategy to develop RNA based drugs with greater therapeutic efficacy.