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

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

Abstract

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. Multiple small interfering RNA (siRNA) molecules were self-assembled and densely packed into composite sponge-like porous microstructures (Multi-RNAi-MSs) by rolling circle transcription. Within each singular microstructure, the stoichiometry of the various polymeric siRNA molecules was precisely controlled 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.

Original languageEnglish
Pages (from-to)3347-3351
Number of pages5
JournalAngewandte Chemie - International Edition
Volume55
Issue number10
DOIs
Publication statusPublished - 2016 Mar 1

Bibliographical note

Funding Information:
We gratefully acknowledge the funding of this work through a DoD OCRP Teal Innovator Award (OC120504). We thank the MIT Koch Institute Swanson Biotechnology Center, which is supported by the Koch Institute Core Grant P30- CA14051 from the NCI, for the use of facilities, specifically the microscopy and flow cytometry cores. This work was supported by the National Research Foundation of Korea (2015R1C1A1A02037770) and by the Yonsei University Future-leading Research Initiative of 2015 (2015-22-0085). This work was also supported by the National Institutes of Health (1F32EB017614-02 to E.C.D.).

Publisher Copyright:
© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)

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