RNAi-microsponges form through self-assembly of the organic and inorganic products of transcription

Kevin E. Shopsowitz, Young Hoon Roh, Zhou J. Deng, Stephen W. Morton, Paula T. Hammond

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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 (Mg2P 2O7•3.5H2O) 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. The structure of microsponges formed during rolling circle transcription is elucidated. These particles consist of RNA adsorbed onto the surface of nanocrystalline magnesium pyrophosphate sheets that self-assemble as RNA and pyrophosphate are produced during transcription. This unique composite structure allows for high loadings of RNA capable of mediating RNAi.

Original languageEnglish
Pages (from-to)1623-1633
Number of pages11
JournalSmall
Volume10
Issue number8
DOIs
Publication statusPublished - 2014 Apr 24

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)

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