Gene therapy of cystic fibrosis: the glycofection approach |
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Authors: | Fajac I Briand P Monsigny M |
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Affiliation: | (1) Laboratoire de Physiologie Respiratoire, CHU Cochin, AP-HP, Université Paris V, Paris, France;(2) ENS-Ulm, Paris, France;(3) Glycobiologie, Centre de Biophysique Moléculaire, CNRS et Université d'Orléans, Orléans, France |
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Abstract: | Many cells express surface membrane lectins that selectively bind and carry glycoconjugates into intracellular endosomes; in addition, various intracellular membrane and soluble lectins act as shuttles between different compartments. On this basis, we developed glycosylated polycations, now called glycofectins (glycosylated polylysine and polyethyleneimine). Recently, we set up a simple way to transform oligosaccharides into glycosynthons suitable to substitute proteins or polymers. Glycofectins bind plasmid DNA leading to compact glycoplexes. Glycoplexes prepared with glycofectins were found to be much more active than naked plasmid to transfer genes to various types of cells including human airway epithelial and serous cells. The gene transfer efficiency was found to depend on the nature of the sugars borne by glycofectins. It appeared that the sugar-dependent efficiency was not only related to the uptake but also to the intracellular traffic of glycoplexes. |
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Keywords: | gene therapy glycoconjugates intracellular traffic glycoplexes polyplexes |
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