Alkane-modified short polyethyleneimine for siRNA delivery

RNA interference (RNAi) is a highly specific gene-silencing mechanism triggered by small interfering RNA (siRNA). Effective intracellular delivery requires the development of potent siRNA carriers. Here, we describe the synthesis and screening of a series of siRNA delivery materials. Short polyethyl...

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Main Authors: Anderson, Daniel, Schroeder, Avraham Dror, Sahay, Gaurav, Love, Kevin T, Jiang, Shan, Levins, Christopher G., Wang, Yingxia, Dahlman, James E., Eltoukhy, Ahmed A.
Other Authors: Harvard University--MIT Division of Health Sciences and Technology
Format: Article
Language:en_US
Published: Elsevier 2017
Online Access:http://hdl.handle.net/1721.1/108141
https://orcid.org/0000-0002-2100-1171
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author Anderson, Daniel
Schroeder, Avraham Dror
Sahay, Gaurav
Love, Kevin T
Jiang, Shan
Levins, Christopher G.
Wang, Yingxia
Dahlman, James E.
Eltoukhy, Ahmed A.
author2 Harvard University--MIT Division of Health Sciences and Technology
author_facet Harvard University--MIT Division of Health Sciences and Technology
Anderson, Daniel
Schroeder, Avraham Dror
Sahay, Gaurav
Love, Kevin T
Jiang, Shan
Levins, Christopher G.
Wang, Yingxia
Dahlman, James E.
Eltoukhy, Ahmed A.
author_sort Anderson, Daniel
collection MIT
description RNA interference (RNAi) is a highly specific gene-silencing mechanism triggered by small interfering RNA (siRNA). Effective intracellular delivery requires the development of potent siRNA carriers. Here, we describe the synthesis and screening of a series of siRNA delivery materials. Short polyethyleneimine (PEI, Mw 600) was selected as a cationic backbone to which lipid tails were conjugated at various levels of saturation. In solution these polymer–lipid hybrids self-assemble to form nanoparticles capable of complexing siRNA. The complexes silence genes specifically and with low cytotoxicity. The efficiency of gene knockdown increased as the number of lipid tails conjugated to the PEI backbone increased. This is explained by reducing the binding affinity between the siRNA strands to the complex, thereby enabling siRNA release after cellular internalization. These results highlight the importance of complexation strength when designing siRNA delivery materials.
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spelling mit-1721.1/1081412022-10-01T09:51:59Z Alkane-modified short polyethyleneimine for siRNA delivery Anderson, Daniel Schroeder, Avraham Dror Sahay, Gaurav Love, Kevin T Jiang, Shan Levins, Christopher G. Wang, Yingxia Dahlman, James E. Eltoukhy, Ahmed A. Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Anderson, Daniel Schroeder, Avraham Dror Dahlman, James Sahay, Gaurav Love, Kevin T Jiang, Shan Eltoukhy, Ahmed Atef Levins, Christopher G. Wang, Yingxia RNA interference (RNAi) is a highly specific gene-silencing mechanism triggered by small interfering RNA (siRNA). Effective intracellular delivery requires the development of potent siRNA carriers. Here, we describe the synthesis and screening of a series of siRNA delivery materials. Short polyethyleneimine (PEI, Mw 600) was selected as a cationic backbone to which lipid tails were conjugated at various levels of saturation. In solution these polymer–lipid hybrids self-assemble to form nanoparticles capable of complexing siRNA. The complexes silence genes specifically and with low cytotoxicity. The efficiency of gene knockdown increased as the number of lipid tails conjugated to the PEI backbone increased. This is explained by reducing the binding affinity between the siRNA strands to the complex, thereby enabling siRNA release after cellular internalization. These results highlight the importance of complexation strength when designing siRNA delivery materials. Misrock Foundation American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowship National Institutes of Health (U.S) (Grant EB000244) National Cancer Institute (U.S.) (MIT-Harvard Center of Cancer Nanotechnology Excellence. Grant CA151884) National Science Foundation (U.S.) Massachusetts Institute of Technology (Presidential Fellowships) 2017-04-13T19:33:19Z 2017-04-13T19:33:19Z 2011-12 2011-09 Article http://purl.org/eprint/type/JournalArticle 0168-3659 http://hdl.handle.net/1721.1/108141 Schroeder, Avi et al. “Alkane-Modified Short Polyethyleneimine for siRNA Delivery.” Journal of Controlled Release 160.2 (2012): 172–176. https://orcid.org/0000-0002-2100-1171 en_US http://dx.doi.org/10.1016/j.jconrel.2011.11.030 Journal of Controlled Release Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC
spellingShingle Anderson, Daniel
Schroeder, Avraham Dror
Sahay, Gaurav
Love, Kevin T
Jiang, Shan
Levins, Christopher G.
Wang, Yingxia
Dahlman, James E.
Eltoukhy, Ahmed A.
Alkane-modified short polyethyleneimine for siRNA delivery
title Alkane-modified short polyethyleneimine for siRNA delivery
title_full Alkane-modified short polyethyleneimine for siRNA delivery
title_fullStr Alkane-modified short polyethyleneimine for siRNA delivery
title_full_unstemmed Alkane-modified short polyethyleneimine for siRNA delivery
title_short Alkane-modified short polyethyleneimine for siRNA delivery
title_sort alkane modified short polyethyleneimine for sirna delivery
url http://hdl.handle.net/1721.1/108141
https://orcid.org/0000-0002-2100-1171
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