A Multi-RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs

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...

Full description

Bibliographic Details
Main Authors: Park, Jae Hyon, Roh, Young Hoon, Dreaden, Erik, Yun, Dong Soo, Shopsowitz, Kevin, Hammond, Paula T, Deng, Zhou J.
Other Authors: Massachusetts Institute of Technology. Department of Chemical Engineering
Format: Article
Language:en_US
Published: Wiley Blackwell 2017
Online Access:http://hdl.handle.net/1721.1/106977
https://orcid.org/0000-0002-4954-8443
https://orcid.org/0000-0003-3988-0837
_version_ 1811080902712754176
author Park, Jae Hyon
Roh, Young Hoon
Dreaden, Erik
Yun, Dong Soo
Shopsowitz, Kevin
Hammond, Paula T
Deng, Zhou J.
author2 Massachusetts Institute of Technology. Department of Chemical Engineering
author_facet Massachusetts Institute of Technology. Department of Chemical Engineering
Park, Jae Hyon
Roh, Young Hoon
Dreaden, Erik
Yun, Dong Soo
Shopsowitz, Kevin
Hammond, Paula T
Deng, Zhou J.
author_sort Park, Jae Hyon
collection MIT
description 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.
first_indexed 2024-09-23T11:38:36Z
format Article
id mit-1721.1/106977
institution Massachusetts Institute of Technology
language en_US
last_indexed 2024-09-23T11:38:36Z
publishDate 2017
publisher Wiley Blackwell
record_format dspace
spelling mit-1721.1/1069772022-09-27T20:58:10Z A Multi-RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs Park, Jae Hyon Roh, Young Hoon Dreaden, Erik Yun, Dong Soo Shopsowitz, Kevin Hammond, Paula T Deng, Zhou J. Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Roh, Young Hoon Deng, Zhou Dreaden, Erik Yun, Dong Soo Shopsowitz, Kevin Hammond, Paula T 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. United States. Department of Defense. Ovarian Cancer Research Program (Teal Innovator Award OC120504) National Research Foundation of Korea (Grant 2015R1C1A1A02037770) Yonsei University (Future-leading Research Initiative 2015-22-0085) National Institutes of Health (U.S.) (Grant 1F32EB017614-02) 2017-02-16T20:15:34Z 2017-02-16T20:15:34Z 2015-12 2015-11 Article http://purl.org/eprint/type/JournalArticle 1433-7851 1521-3773 http://hdl.handle.net/1721.1/106977 Roh, Young Hoon et al. “A Multi-RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs.” Angewandte Chemie International Edition 55.10 (2016): 3347–3351. https://orcid.org/0000-0002-4954-8443 https://orcid.org/0000-0003-3988-0837 en_US http://dx.doi.org/10.1002/anie.201508978 Angewandte Chemie International Edition Creative Commons Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ application/pdf Wiley Blackwell Wiley
spellingShingle Park, Jae Hyon
Roh, Young Hoon
Dreaden, Erik
Yun, Dong Soo
Shopsowitz, Kevin
Hammond, Paula T
Deng, Zhou J.
A Multi-RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs
title A Multi-RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs
title_full A Multi-RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs
title_fullStr A Multi-RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs
title_full_unstemmed A Multi-RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs
title_short A Multi-RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs
title_sort multi rnai microsponge platform for simultaneous controlled delivery of multiple small interfering rnas
url http://hdl.handle.net/1721.1/106977
https://orcid.org/0000-0002-4954-8443
https://orcid.org/0000-0003-3988-0837
work_keys_str_mv AT parkjaehyon amultirnaimicrospongeplatformforsimultaneouscontrolleddeliveryofmultiplesmallinterferingrnas
AT rohyounghoon amultirnaimicrospongeplatformforsimultaneouscontrolleddeliveryofmultiplesmallinterferingrnas
AT dreadenerik amultirnaimicrospongeplatformforsimultaneouscontrolleddeliveryofmultiplesmallinterferingrnas
AT yundongsoo amultirnaimicrospongeplatformforsimultaneouscontrolleddeliveryofmultiplesmallinterferingrnas
AT shopsowitzkevin amultirnaimicrospongeplatformforsimultaneouscontrolleddeliveryofmultiplesmallinterferingrnas
AT hammondpaulat amultirnaimicrospongeplatformforsimultaneouscontrolleddeliveryofmultiplesmallinterferingrnas
AT dengzhouj amultirnaimicrospongeplatformforsimultaneouscontrolleddeliveryofmultiplesmallinterferingrnas
AT parkjaehyon multirnaimicrospongeplatformforsimultaneouscontrolleddeliveryofmultiplesmallinterferingrnas
AT rohyounghoon multirnaimicrospongeplatformforsimultaneouscontrolleddeliveryofmultiplesmallinterferingrnas
AT dreadenerik multirnaimicrospongeplatformforsimultaneouscontrolleddeliveryofmultiplesmallinterferingrnas
AT yundongsoo multirnaimicrospongeplatformforsimultaneouscontrolleddeliveryofmultiplesmallinterferingrnas
AT shopsowitzkevin multirnaimicrospongeplatformforsimultaneouscontrolleddeliveryofmultiplesmallinterferingrnas
AT hammondpaulat multirnaimicrospongeplatformforsimultaneouscontrolleddeliveryofmultiplesmallinterferingrnas
AT dengzhouj multirnaimicrospongeplatformforsimultaneouscontrolleddeliveryofmultiplesmallinterferingrnas