Folate-Equipped Nanolipoplexes Mediated Efficient Gene Transfer into Human Epithelial Cells
AbstractSince recombinant viral vectors have been associated with serious side effects, such as immunogenicity and oncogenicity, synthetic delivery systems represent a realistic alternative for achieving efficacy in gene therapy. A major challenge for non-viral nanocarriers is the optimization of transgene expression in the targeted cells. This goal can be achieved by fine-tuning the chemical carriers and the adding specific motifs to promote cellular penetration. Our study focuses on the development of novel folate-based complexes that contain varying quantities of folate motifs. After controlling for their physical properties, neutral folate-modified lipid formulations were compared in vitro to lipoplexes leading to comparable expression levels. In addition, no cytotoxicity was detected, unlike what was observed in the cationic controls. Mechanistically, the delivery of the transgene appeared to be, in part, due to endocytosis mediated by folate receptor targeting. This mechanism was further validated by the observation that adding free folate into the medium decreased luciferase expression by 50%. In vivo transfection with the folate-modified MM18 lipid, containing the highest amount of FA-PEG570-diether co-lipid (w:w; 90:10), at a neutral charge ratio, gave luciferase transgene expression. These studies indicate that modification of lipids with folate residues could enhance non-toxic, cell-specific gene delivery. View Full-Text
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Mornet, E.; Carmoy, N.; Lainé, C.; Lemiègre, L.; Le Gall, T.; Laurent, I.; Marianowski, R.; Férec, C.; Lehn, P.; Benvegnu, T.; Montier, T. Folate-Equipped Nanolipoplexes Mediated Efficient Gene Transfer into Human Epithelial Cells. Int. J. Mol. Sci. 2013, 14, 1477-1501.
Mornet E, Carmoy N, Lainé C, Lemiègre L, Le Gall T, Laurent I, Marianowski R, Férec C, Lehn P, Benvegnu T, Montier T. Folate-Equipped Nanolipoplexes Mediated Efficient Gene Transfer into Human Epithelial Cells. International Journal of Molecular Sciences. 2013; 14(1):1477-1501.Chicago/Turabian Style
Mornet, Emmanuel; Carmoy, Nathalie; Lainé, Céline; Lemiègre, Loïc; Le Gall, Tony; Laurent, Isabelle; Marianowski, Remi; Férec, Claude; Lehn, Pierre; Benvegnu, Thierry; Montier, Tristan. 2013. "Folate-Equipped Nanolipoplexes Mediated Efficient Gene Transfer into Human Epithelial Cells." Int. J. Mol. Sci. 14, no. 1: 1477-1501.