Cystic fibrosis gene therapy with recombinant adenovirus: A long way to go

The identification of the gene on which mutations cause cystic fibrosis has opened the way to the concept of gene therapy of this disease. Somatic gene therapy for cystic fibrosis should be directed to the epithelial cells of the bronchi where the biological defect is the most deleterious. In order to have the normal DNA coding sequence penetrate the bronchial epithelial cells of a patient, a gene vector is necessary, and recombinant adenoviruses have been the subject of extensive studies in this regard. Data are available from many laboratories as well as from several phase I clinical trials. Successes and limits of this approach are reviewed here. The advantage of nan-viral vectors, in particular cationic liposomes, as an alternative to recombinant adenoviruses is briefly discussed. Significant advances still need to be made before gene therapy becomes a reality in cystic fibrosis. These future improvements should include the construction of more efficient gene vectors, and also the development of better tools for the evaluation of a biological effect of gene therapy in individual patients.