Composite RNAi-Microsponges Form through Self-Assembly of the Organic and Inorganic Products of Transcription
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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | en_US |
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Wiley Blackwell
2014
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| Online Access: | http://hdl.handle.net/1721.1/91594 https://orcid.org/0000-0003-3988-0837 |
| _version_ | 1811071436192743424 |
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| author | Roh, Young Hoon Deng, Zhou J. Shopsowitz, Kevin Morton, Stephen Winford Hammond, Paula T |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Roh, Young Hoon Deng, Zhou J. Shopsowitz, Kevin Morton, Stephen Winford Hammond, Paula T |
| author_sort | Roh, Young Hoon |
| collection | MIT |
| description | 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[subscript 2]P[subscript 2]O[subscript 7]•3.5H[subscript 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. |
| first_indexed | 2024-09-23T08:50:55Z |
| format | Article |
| id | mit-1721.1/91594 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:50:55Z |
| publishDate | 2014 |
| publisher | Wiley Blackwell |
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| spelling | mit-1721.1/915942022-09-30T11:40:46Z Composite RNAi-Microsponges Form through Self-Assembly of the Organic and Inorganic Products of Transcription RNAi-Microsponges Form through Self-Assembly of the Organic and Inorganic Products of Transcription Roh, Young Hoon Deng, Zhou J. Shopsowitz, Kevin Morton, Stephen Winford Hammond, Paula T Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Shopsowitz, Kevin Roh, Young Hoon Deng, Zhou J. Morton, Stephen Winford Hammond, Paula T. 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[subscript 2]P[subscript 2]O[subscript 7]•3.5H[subscript 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. National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051) National Cancer Institute (U.S.) (Center for Cancer Nanotechnology Excellence Grant 5 U54 CA151884-02) Natural Sciences and Engineering Research Council of Canada (Postdoctoral Fellowship) National Health and Medical Research Council (Australia) (CJ Martin Fellowship) National Science Foundation (U.S.). Graduate Research Fellowship 2014-11-17T17:57:31Z 2014-11-17T17:57:31Z 2013-12 2013-10 Article http://purl.org/eprint/type/JournalArticle 16136810 1613-6829 http://hdl.handle.net/1721.1/91594 Shopsowitz, Kevin E., Young Hoon Roh, Zhou J. Deng, Stephen W. Morton, and Paula T. Hammond. “RNAi-Microsponges Form through Self-Assembly of the Organic and Inorganic Products of Transcription.” Small 10, no. 8 (December 19, 2013): 1623–1633. https://orcid.org/0000-0003-3988-0837 en_US http://dx.doi.org/10.1002/smll.201302676 Small Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Blackwell PMC |
| spellingShingle | Roh, Young Hoon Deng, Zhou J. Shopsowitz, Kevin Morton, Stephen Winford Hammond, Paula T Composite RNAi-Microsponges Form through Self-Assembly of the Organic and Inorganic Products of Transcription |
| title | Composite RNAi-Microsponges Form through Self-Assembly of the Organic and Inorganic Products of Transcription |
| title_full | Composite RNAi-Microsponges Form through Self-Assembly of the Organic and Inorganic Products of Transcription |
| title_fullStr | Composite RNAi-Microsponges Form through Self-Assembly of the Organic and Inorganic Products of Transcription |
| title_full_unstemmed | Composite RNAi-Microsponges Form through Self-Assembly of the Organic and Inorganic Products of Transcription |
| title_short | Composite RNAi-Microsponges Form through Self-Assembly of the Organic and Inorganic Products of Transcription |
| title_sort | composite rnai microsponges form through self assembly of the organic and inorganic products of transcription |
| url | http://hdl.handle.net/1721.1/91594 https://orcid.org/0000-0003-3988-0837 |
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