Self-assembled DNA-Guided RNA Nanovector via Step-wise Dual Enzyme Polymerization (SDEP) for Carrier-free siRNA Delivery.

Nucleic acid-based therapeutics are being used increasingly for biomedical applications. Despite this, the development of nontoxic and cell-targetable delivery systems for practical use is still a challenge. This paper reports a novel enzymatic synthetic approach to produce cell-targetable RNA nanovectors. The RNA nanovectors were generated by the hybridization of DNA and RNA strands produced by temperature-dependent dual polymerization, which is also called stepwise dual enzyme polymerization. The RNA strands are designed to contain siRNA precursors, and the DNA strands include aptamers that bind specifically to the target molecules for cell-targeting. The RNA nanovector can also enhance the resistance to nuclease degradation and help overcome the limitations associated with the nature of RNA via DNA-RNA hybrids. Therefore, the proposed strategy, stepwise dual enzyme polymerization, is an innovative solution for successful carrier-free siRNA delivery.