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A Multi‐RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs
Author(s) -
Roh Young Hoon,
Deng Jason Z.,
Dreaden Erik C.,
Park Jae Hyon,
Yun Dong Soo,
Shopsowitz Kevin E.,
Hammond Paula T.
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201508978
Subject(s) - rna interference , small interfering rna , rna , nanotechnology , small molecule , materials science , chemistry , biology , biophysics , microbiology and biotechnology , biochemistry , gene
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.