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Palmitic Acid-Modified Poly-l-Lysine for Non-Viral Delivery of Plasmid DNA to Skin Fibroblasts

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journal contribution
posted on 09.04.2007, 00:00 by Meysam Abbasi, Hasan Uludaǧ, Vanessa Incani, Cori Olson, Xiaoyue Lin, Başak Açan Clements, Dorothy Rutkowski, Aziz Ghahary, Michael Weinfeld
Palmitic acid conjugates of poly-l-lysine (PLL-PA) were prepared, and their ability to deliver plasmid DNA into human skin fibroblasts was evaluated in vitro. The conjugates were capable of condensing a 4.7 kb plasmid DNA into 50−200 nm particles (mean ± SD = 112 ± 34 nm), which were slightly smaller than the particles formed by PLL (mean ± SD = 126 ± 51 nm). Both PLL and PLL-PA were readily taken up by the cells, but PLL-PA delivered the plasmid DNA into a higher proportion of cells. DNA delivery was found to be reduced by endocytosis inhibitor Brefeldin A, suggesting an active mechanism of particle uptake. Using enhanced green fluorescent protein (EGFP) as a reporter gene, PLL-PA was found to give the highest number of EGFP-positive cells among several carriers tested, including polyethyleneimine, Lipofectamine-2000, and an adenovirus. Although some carriers gave a higher percentage of EGFP-positive cells than PLL-PA, they were also associated with higher toxicities. We conclude that PLL-PA is a promising gene carrier for non-viral modification of human fibroblasts.