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Multiple and time-scheduled in situ DNA delivery mediated by ß-cyclodextrin embedded in a polyelectrolyte multilayer

Year: 2006

Journal: PNAS, June 6, 2006, vol. 103, no. 23, 8618–8621, 20100827

Authors: Jessel N., Oulad-Abdelghani M., Meyer F., Lavalle P., Haikel Y., Schaaf P., Voegel J.-C.

Last authors: J.-C. Voegel

Organizations: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 595, Faculté de Médecine, 11 Rue Humann, 67085 Strasbourg Cedex, France and Faculté de Chirurgie Dentaire de l’Université Louis Pasteur (ULP), 67000 Strasbourg Cedex, France; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut Clinique de la Souris (ICS), Centre National de la Recherche Scientifique (CNRS)/INSERM/ULP, Collège de France, BP10142, 67404 Strasbourg, France; and §Institut Charles Sadron (CNRS/ULP), 6 Rue Boussingault, 67083 Strasbourg Cedex, France

Country: France

The basic premise of gene therapy is that genes can be used to produce in situ therapeutic proteins. The controlled delivery of DNA complexes from biomaterials offers the potential to enhance gene transfer by maintaining an elevated concentration of DNA within the cellular microenvironment. Immobilization of the DNA to the substrate to which cells adhere maintains the DNA in the cell microenvironment for subsequent cellular internalization. Here, layer-by-layer (LBL) films made from poly(L-glutamic acid) (PLGA) and poly(L-lysine) (PLL) containing DNA were built in the presence of charged cyclodextrins. The biological activities of these polyelectrolyte films were tested by means of induced production of a specific protein in the nucleus or in the cytoplasm by cells in contact with the films. This type of coating offers the possibility for either simultaneous or sequential interfacial delivery of different DNA molecules aimed at cell transfection. These results open the route to numerous potential applications in patch vaccination, for example.