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- Title
Highly Effective Gene Transfection In Vivo by Alkylated Polyethylenimine.
- Authors
Fortune, Jennifer A.; Novobrantseva, Tatiana I.; Klibanov, Alexander M.
- Abstract
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.
- Subjects
GENE transfection; GENE expression; ALKYLATION; LABORATORY mice; ETHYLATION; MEDICAL polymers; POLYETHYLENE
- Publication
Journal of Drug Delivery, 2011, p1
- ISSN
2090-3014
- Publication type
Article
- DOI
10.1155/2011/204058