Development in nucleic acid nanotechnology has been attracted with their therapeutic functions and nontoxicity. As one of them, rolling circle replication (RCR) has been considered as a powerful tool to synthesize various nucleic acid-based architectures. We developed a novel enzymatic synthetic approach to produce cell-targetable DNA-RNA hybrid nanovectors. This material was generated by the dual enzyme polymerization, especially rolling circle amplification (RCA) for DNA and rolling circle transcription (RCT) for RNA with enhanced resistance to nuclease degradation compared to the natural DNA and RNA. DNA strands contains tumor-specific aptamer sequence and RNA strands includes the siRNA precursors resulting in the carrier-free tumor-targeted siRNA delivery. In further steps, DNA-supported RNA hydrogel embedding the therapeutic RNA particles was also fabricated. In previous studies, there are few reports in regard to RNA hydrogel due to the structural instability. To overcome this limitation, we employed dual polymerization resulting in macroscale RNA-based structure. This hydrogel is produced by self-assembly of DNA and RNA and their direct hybridization. This system is considered as a smart double-sustained release of RNA particles from hydrogel then siRNA from the particles. As a proof of concept, the hydrogel was applied to tumor-targeted green fluorescence protein (GFP) silencing assay by the double-releasing system in physiological condition. Taken together, our strategy for the synthesis of DNA-RNA hybrid materials has high potential to capacitate further exploration in gene and cancer therapy.

DNA-RNA hybrid materials via dual enzyme polymerization for carrier-free therapeutic RNA delivery

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.