Highly Effective Gene Transfection In Vivo by Alkylated Polyethylenimine
We mechanistically explored the effect of increased hydrophobicity of the polycation on the efficacy and specificity of gene delivery in mice. N-Alkylated linear PEIs with varying alkyl chain lengths and extent of substitution were synthesized and characterized by biophysical methods. Their in vivo...
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| Format: | Article |
| Language: | en_US |
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Hindawi Pub. Corp.
2011
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| Online Access: | http://hdl.handle.net/1721.1/64795 https://orcid.org/0000-0003-3830-714X |
| _version_ | 1811094276184997888 |
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| author | Fortune, Jennifer A. Novobrantseva, Tatiana I. Klibanov, Alexander M. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Fortune, Jennifer A. Novobrantseva, Tatiana I. Klibanov, Alexander M. |
| author_sort | Fortune, Jennifer A. |
| collection | MIT |
| description | We mechanistically explored the effect of increased hydrophobicity of the polycation on the efficacy and specificity of gene delivery in mice. N-Alkylated linear PEIs with varying alkyl chain lengths and extent of substitution were synthesized and characterized by biophysical methods. Their in vivo transfection efficiency, specificity, and biodistribution were investigated. N-Ethylation improves the in vivo efficacy of gene expression in the mouse lung 26-fold relative to the parent polycation and more than quadruples the ratio of expression in the lung to that in all other organs. N-Propyl-PEI was the best performer in the liver and heart (581- and 3.5-fold enhancements, resp.) while N-octyl-PEI improved expression in the kidneys over the parent polymer 221-fold. As these enhancements in gene expression occur without changing the plasmid biodistribution, alkylation does not alter the cellular uptake but rather enhances transfection subsequent to cellular uptake. |
| first_indexed | 2024-09-23T15:57:07Z |
| format | Article |
| id | mit-1721.1/64795 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:57:07Z |
| publishDate | 2011 |
| publisher | Hindawi Pub. Corp. |
| record_format | dspace |
| spelling | mit-1721.1/647952022-10-02T05:19:22Z Highly Effective Gene Transfection In Vivo by Alkylated Polyethylenimine Fortune, Jennifer A. Novobrantseva, Tatiana I. Klibanov, Alexander M. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemistry Klibanov, Alexander M Fortune, Jennifer A. Klibanov, Alexander M. We mechanistically explored the effect of increased hydrophobicity of the polycation on the efficacy and specificity of gene delivery in mice. N-Alkylated linear PEIs with varying alkyl chain lengths and extent of substitution were synthesized and characterized by biophysical methods. Their in vivo transfection efficiency, specificity, and biodistribution were investigated. N-Ethylation improves the in vivo efficacy of gene expression in the mouse lung 26-fold relative to the parent polycation and more than quadruples the ratio of expression in the lung to that in all other organs. N-Propyl-PEI was the best performer in the liver and heart (581- and 3.5-fold enhancements, resp.) while N-octyl-PEI improved expression in the kidneys over the parent polymer 221-fold. As these enhancements in gene expression occur without changing the plasmid biodistribution, alkylation does not alter the cellular uptake but rather enhances transfection subsequent to cellular uptake. National Institutes of Health (U.S.) (NIH Grant 2-R37-EB000244-29) National Science Foundation (U.S.) (NSF-0070319 ) National Institutes of Health (U.S.) (NIH GM68762) 2011-07-13T19:01:44Z 2011-07-13T19:01:44Z 2011-01 2011-01 Article http://purl.org/eprint/type/JournalArticle 2090-3022 http://hdl.handle.net/1721.1/64795 Jennifer A. Fortune, Tatiana I. Novobrantseva, and Alexander M. Klibanov, “Highly Effective Gene Transfection In Vivo by Alkylated Polyethylenimine,” Journal of Drug Delivery, vol. 2011, Article ID 204058, 6 pages, 2011. https://orcid.org/0000-0003-3830-714X en_US http://dx.doi.org/10.1155/2011/204058 Journal of Drug Delivery Creative Commons Attribution http://creativecommons.org/licenses/by/2.0/ application/pdf Hindawi Pub. Corp. Hindawi |
| spellingShingle | Fortune, Jennifer A. Novobrantseva, Tatiana I. Klibanov, Alexander M. Highly Effective Gene Transfection In Vivo by Alkylated Polyethylenimine |
| title | Highly Effective Gene Transfection In Vivo by Alkylated Polyethylenimine |
| title_full | Highly Effective Gene Transfection In Vivo by Alkylated Polyethylenimine |
| title_fullStr | Highly Effective Gene Transfection In Vivo by Alkylated Polyethylenimine |
| title_full_unstemmed | Highly Effective Gene Transfection In Vivo by Alkylated Polyethylenimine |
| title_short | Highly Effective Gene Transfection In Vivo by Alkylated Polyethylenimine |
| title_sort | highly effective gene transfection in vivo by alkylated polyethylenimine |
| url | http://hdl.handle.net/1721.1/64795 https://orcid.org/0000-0003-3830-714X |
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