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Problem Addressed

Short interfering RNAs (siRNAs) have great therapeutic potential but clinical translation has been hindered by poor in vivo stability, low loading efficiency, and dose-limiting toxicity. The generation of periodic short hairpin RNA (concatemeric siRNA) via rolling circle transcription (RCT) of a dumbbell shaped DNA template, which may be processed by Dicer proteins into siRNAs, has been reported as an alternative source of RNA interference. However, due to a lack of open ends, Dicer cleavage of periodic short hairpin RNA (p-shRNA) is inefficient. This invention is a more stable, cleavable p-shRNA containing open ends for efficient Dicer processing enabling high silencing efficacy with smaller amounts of delivery materials.