[Gene therapy in mucoviscidosis]

Treatment of the respiratory manifestations of cystic fibrosis requires a wide therapeutic effort. In this respect, gene therapy is a promising alternative approach. Following the cloning of the gene encoding the cystic fibrosis transmembrane conductance regulator protein (CFTR), whose malfunction or absence lead to the disease phenotype, a particular effort has been undertaken in order to validate several gene delivery systems in vitro and in vivo. Recombinant adenovirus and adeno-associated virus as well as plasmid DNA associated to cationic lipids (liposomes) have been used as vectors. Their efficiency and safety have been demonstrated in several animal models. Recombinant adenovirus containing the CFTR cDNA (Ad CFTR) and liposomes containing DNA expressing CFTR have been instilled into the nose and lungs of several cystic fibrosis patients. Aerosol delivery of Ad CFTR has also been performed with success in six patients. Transfer of the CFTR gene as well as its expression were demonstrated. In a few cases transient correction of the defective transepithelial Cl- transport in the cystic fibrosis nasal mucosa was demonstrated. At present several strategies are under way to improve the safety and the persistence of CFTR expression of the different vector systems.