NASAL APPLICATION OF THE CATIONIC LIPOSOME DC-CHOL-DOPE DOES NOT ALTER ION-TRANSPORT, LUNG-FUNCTION OR BACTERIAL-GROWTH

Liposome-mediated gene transfer is commonly used for in vitro transfec tion of deoxyribonucleic acid (DNA) into mammalian cells. We and other s have recently demonstrated that this can be an effective method for in vivo delivery of plasmid DNA containing the human cystic fibrosis t ransmembrane conductance regulator (CFTR) gene to mouse models of cyst ic fibrosis (CF). This suggests that cationic liposomes may be useful for transferring CFTR complementary DNA (cDNA) into the airways of CF subjects. In this study, measurement of nasal potential difference (PD ) was used to monitor the efficacy of correction of the CF bioelectric defect and to provide a sensitive assay of epithelial integrity. We t herefore assessed whether the cationic liposome DC-Chol:DOPE altered n asal ion transport parameters, in six normal and three CF subjects. Lu ng function was also measured as a further marker of safety. Finally, as CF airways are chronically infected, we studied whether DC-Chol:DOP E or DC-Chol:DOPE-DNA complexes altered the bacterial growth and sensi tivities of CF sputum. No significant effect was seen on any of these parameters, suggesting that DC-Chol:DOPE may be appropriate for use in human trials of liposome-mediated gene therapy for CF.