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Increased Receptor-Mediated Gene Delivery To The Liver By Protamine-Enhanced-Asialofetuin-Lipoplexes, M. A. Arangoa, Nejat Düzgüneş, C. Tros De Ilarduya
Increased Receptor-Mediated Gene Delivery To The Liver By Protamine-Enhanced-Asialofetuin-Lipoplexes, M. A. Arangoa, Nejat Düzgüneş, C. Tros De Ilarduya
All Dugoni School of Dentistry Faculty Articles
A novel lipidic vector composed of DOTAP/Chol liposomes, asialofetuin (AF), protamine sulfate and DNA has been developed. The resulting protamine-AF-lipoplexes improved significantly the levels of gene expression in cultured cells and in the liver upon i.v. administration. Lipoplexes containing the optimal amount of AF (1 μg/μg DNA) showed a 16-fold higher transfection activity in HepG2 cells than non-targeted (plain) complexes. The uptake by cells having asialoglycoprotein receptors (ASGPr) on their plasma membrane was decreased by the addition of free AF, indicating that AF-lipoplexes were taken up specifically by cells via ASGPr-mediated endocytosis. Results from transfections performed in cells defective in …