GENE-TRANSFER BY GUANIDINIUM-CHOLESTEROL CATIONIC LIPIDS INTO AIRWAY EPITHELIAL-CELLS IN-VITRO AND IN-VIVO

Synthetic vectors represent an attractive alternative approach to vira l vectors for gene transfer, in particular into airway epithelial cell s for lung-directed gene therapy for cystic fibrosis. Having recently found that guanidinium-cholesterol cationic lipids are efficient reage nts for gene transfer into mammalian cell lines in vitro, we have inve stigated their use for gene delivery into primary airway epithelial ce lls in vitro and in vivo. The results obtained indicate that the lipid his (guanidinium)-tren-cholesterol (BGTC) can be used to transfer a r eporter gene into primary human air way epithelial cells in culture, F urthermore, liposomes composed of BGTC and dioleoyl phosphatidylethano lamine (DOPE) are efficient for gene delivery to the mouse airway epit helium in vivo. Transfected cells were detected both in the surface ep ithelium and in submucosal glands. In addition, the transfection effic iency of BGTC/DOPE liposomes in vivo was quantitatively assessed by us ing the luciferase reporter gene system.