A Multi-RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs.

Young Hoon Roh, Jason Z Deng, Erik C Dreaden, Jae Hyon Park, Dong Soo Yun, Kevin E Shopsowitz, Paula T Hammond

Angewandte Chemie (International ed. in English) 2016 Mar 01

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Packaging multiple small interfering RNA (siRNA) molecules into nanostructures at precisely defined ratios is a powerful delivery strategy for effective RNA interference (RNAi) therapy. We present a novel RNA nanotechnology based approach to produce multiple components of polymerized siRNA molecules that are simultaneously self-assembled and densely packaged into composite sponge-like porous microstructures (Multi-RNAi-MSs) by rolling circle transcription. The Multi-RNAi-MSs were designed to contain a combination of multiple polymeric siRNA molecules with precisely controlled stoichiometry within a singular microstructure by manipulating the types and ratios of the circular DNA templates. The Multi-RNAi-MSs were converted into nanosized complexes by polyelectrolyte condensation to manipulate their physicochemical properties (size, shape, and surface charge) for favorable delivery, while maintaining the multifunctional properties of the siRNAs for combined therapeutic effects. These Multi-RNAi-MS systems have great potential in RNAi-mediated biomedical applications, for example, for the treatment of cancer, genetic disorders, and viral infections. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Citation

Young Hoon Roh, Jason Z Deng, Erik C Dreaden, Jae Hyon Park, Dong Soo Yun, Kevin E Shopsowitz, Paula T Hammond. A Multi-RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs. Angewandte Chemie (International ed. in English). 2016 Mar 01;55(10):3347-51