Perspectives ex vivo et in vivo pour la thérapie génique, de la transfection sélective à l'aide de complexes plasmide-polylysine ciblés

Abstract

Gene therapy will be an ideal method when it is possible to transfer DNA in cells with a great efficacy and an absolute safety in vivo. Along with viral carriers which are efficient but may not be strictly safe, non viral carriers could be advantageously used. Polylysine, a polycation giving stable DNA complexes, is proposed as the basis of such a carrier system. Indeed, polylysine substituted with either a protein easily taken up by cells due to specific cell surface receptors, or carbohydrate moieties which selectively interact with lectins expressed at the surface of specific cells, allows a cell specific delivery of genes. In addition, when such a targeted carrier is used together with components that protect the plasmid- targeted polylysine complex from the hydrolytic activities of lysosomes and/or help the complex to cross the cell membranes to reach the cytosol, the specificity and the efficacy of the transfection are conspicuously higher.