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Bioengineering 2015, 2(3), 160-175; doi:10.3390/bioengineering2030160

In Vivo GFP Knockdown by Cationic Nanogel-siRNA Polyplexes

1
Department of Biomedical Engineering, Carnegie Mellon University, 700 Technology Dr., Pittsburgh, PA 15219, USA
2
School of Dentistry, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109, USA
3
Department of Chemistry, Carnegie Mellon University, 4400 Fifth Ave., Pittsburgh, PA 15213, USA
Current address (A.R.S.): School of Engineering and Applied Sciences, Harvard University, 29 Oxford St., Cambridge, MA 02138, USA.
*
Author to whom correspondence should be addressed.
Academic Editor: Anthony Guiseppi-Elie
Received: 26 April 2015 / Revised: 6 July 2015 / Accepted: 17 July 2015 / Published: 22 July 2015
View Full-Text   |   Download PDF [6121 KB, uploaded 22 July 2015]   |  

Abstract

RNA interference (RNAi) is a powerful tool to treat diseases and elucidate target gene function. Prior to clinical implementation, however, challenges including the safe, efficient and targeted delivery of siRNA must be addressed. Here, we report cationic nanogel nanostructured polymers (NSPs) prepared by atom transfer radical polymerization (ATRP) for in vitro and in vivo siRNA delivery in mammalian models. Outcomes from siRNA protection studies suggested that nanogel NSPs reduce enzymatic degradation of siRNA within polyplexes. Further, the methylation of siRNA may enhance nuclease resistance without compromising gene knockdown potency. NSP-mediated RNAi treatments against Gapdh significantly reduced GAPDH enzyme activity in mammalian cell culture models supplemented with 10% serum. Moreover, nanogel NSP-mediated siRNA delivery significantly inhibited in vivo GFP expression in a mouse model. GFP knockdown was siRNA sequence-dependent and facilitated by nanogel NSP carriers. Continued testing of NSP/siRNA compositions in disease models may produce important new therapeutic options for patient care. View Full-Text
Keywords: gene therapy; gene expression; RNA Interference; siRNA; GFP; ATRP; nanostructured polymer gene therapy; gene expression; RNA Interference; siRNA; GFP; ATRP; nanostructured polymer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Shrivats, A.R.; Mishina, Y.; Averick, S.; Matyjaszewski, K.; Hollinger, J.O. In Vivo GFP Knockdown by Cationic Nanogel-siRNA Polyplexes. Bioengineering 2015, 2, 160-175.

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