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RNAi‐Microsponges Form through Self‐Assembly of the Organic and Inorganic Products of Transcription
Author(s) -
Shopsowitz Kevin E.,
Roh Young Hoon,
Deng Zhou J.,
Morton Stephen W.,
Hammond Paula T.
Publication year - 2014
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201302676
Subject(s) - rna interference , rna , inorganic pyrophosphatase , nucleic acid , transcription (linguistics) , nanoparticle , chemistry , pyrophosphate , biophysics , materials science , biochemistry , biology , nanotechnology , enzyme , gene , linguistics , philosophy
Inorganic nanostructures have been used extensively to package nucleic acids into forms useful for therapeutic applications. Here we report that the two products of transcription, RNA and inorganic pyrophosphate, can self‐assemble to form composite microsponge structures composed of nanocrystalline magnesium pyrophosphate sheets (Mg 2 P 2 O 7 •3.5H 2 O) with RNA adsorbed to their surfaces. The microsponge particles contain high loadings of RNA (15–21 wt.%) that are protected from degradation and can be obtained through a rolling circle mechanism as large concatemers capable of mediating RNAi. The morphology of the RNAi microsponges is influenced by the time‐course of the transcription reaction and interactions between RNA and the inorganic phase. Previous work demonstrated that polycations can be used to condense RNAi microsponges into nanoparticles capable of efficient transfection with low toxicity. Our new findings suggest that the formation of these nanoparticles is mediated by the gradual dissolution of magnesium pyrophosphate that occurs in the presence of polycations. The simple one‐pot approach for assembling RNAi microsponges along with their unique properties could make them useful for RNA‐based therapeutics.