SOMATIC GENE-THERAPY FOR CYSTIC-FIBROSIS

There is considerable potential to ameliorate the pulmonary disease in cystic fibrosis (CF) using somatic gene therapy. Even low levels of e xpression of the gene in airways epithelium may be beneficial. Adenovi ral vectors, DNA-liposome complexes, adeno-associated viral vectors, a nd DNA-ligand complexes have been used effectively in vitro and have b een tested in animals to varying extent. Adenoviral vectors and DNA-li posome complexes are being used to deliver the CF gene to patient airw ays in phase I clinical trials. Transient correction of the electrophy siological defect in human CF nasal epithelium has been achieved. Majo r goals are (i) to demonstrate that expression of the CF gene in airwa ys epithelium will ameliorate lung disease in CF patients, and (ii) to achieve long-term expression of the introduced gene either through a single delivery with persistent expression or through the ability to u se a delivery system repetitively with safety and efficacy.