Polycations increase the efficiency of adenovirus-mediated gene transfer to epithelial and endothelial cells in vitro
| Autor: | M Gondor, Selim M. Arcasoy, Joseph M. Pilewski, Joseph D. Latoche, Bruce R. Pitt |
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| Rok vydání: | 1997 |
| Předmět: |
polycations
Cystic Fibrosis Genetic enhancement Genetic Vectors Cell Gene Expression Biology Kidney medicine.disease_cause Article Epithelium Adenoviridae Dogs Genes Reporter Cations Gene expression Escherichia coli Genetics medicine Animals Humans Transgenes Molecular Biology Cells Cultured Sheep Genetic transfer Gene Transfer Techniques Thrombosis gene therapy glycoconjugates Cell biology Endothelial stem cell Membrane glycoproteins medicine.anatomical_structure Lac Operon Cell culture vascular thrombosis Immunology biology.protein Molecular Medicine Endothelium Vascular |
| Zdroj: | Gene Therapy |
| ISSN: | 1476-5462 0969-7128 |
| DOI: | 10.1038/sj.gt.3300349 |
| Popis: | Recombinant adenoviruses are being developed for gene therapy for cystic fibrosis and other lung diseases, and for prevention and treatment of vascular thrombosis. A major limitation to the clinical utility of adenoviruses is the low efficiency of gene transfer achieved in vivo. In addition, little is known about the initial interactions between adenoviruses and the target cell. To address the hypothesis that the negative charge presented by membrane glycoproteins reduces the efficiency of adenovirus-mediated gene transfer, primary cultures of human airway, Madin-Darby canine kidney cells, an immortalized cystic fibrosis airway epithelial cell line, and primary cultures of sheep pulmonary artery endothelium were infected with recombinant adenovirus containing the E. coli lacZ reporter gene (Ad2 beta gal2) in the presence of various polyions. For each cell type, adsorption of Ad2 beta gal2 in the presence of the polycations polybrene, protamine, DEAE-dextran, and poly-L-lysine significantly increased the percentage of cells that express lacZ. The polyanion heparin did not significantly alter gene transfer efficiency, but completely abrogated the effects of polycations. These data provide evidence that negatively charged moieties on the cell surface reduce the efficiency of adenovirus-mediated gene transfer, and that alteration of the charge interaction between adenoviruses and the cell surface may improve the potential clinical application of these vectors. |
| Databáze: | OpenAIRE |
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