A bivalent aptamer and terminus-free siRNA junction nanostructure for targeted gene silencing in cancer cells.

Small interfering RNA (siRNA) has increasingly evolved as a potent therapeutic solution for several pathological conditions including cancers via post-transcriptional oncogene suppression in cellular pathways. And, the key for siRNA-based therapy highly relies on the successful siRNAs delivery into the target cells, which is significantly challenged by their instability, poor cellular uptake and targeting capability. To overcome these issues, herein, a new type of RNA nanostructure, the bivalent aptamer and terminus-free siRNA junction, is synthesized and employed for effective gene silencing in cancer cells. Such a siRNA junction can be readily prepared by the self-assembly of three RNA sequences and subsequent ligation of the nicks. The as-synthesized siRNA junction shows highly improved enzymatic stability and targeting capability and can be efficiently delivered into the target cells to induce cell apoptosis. With these integrated advantages, the siRNA junction can therefore offer new potentials for the design of different siRNA therapeutics for various diseases.