Highly Effective Gene Transfection In Vivo by Alkylated Polyethylenimine

  • Fortune J
  • Novobrantseva T
  • Klibanov A
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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.

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Fortune, J. A., Novobrantseva, T. I., & Klibanov, A. M. (2011). Highly Effective Gene Transfection In Vivo by Alkylated Polyethylenimine . Journal of Drug Delivery, 2011, 1–6. https://doi.org/10.1155/2011/204058

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