Gene transfection into the mouse airways using novel pegylated cationic lipid formulations

Cationic lipids are at present actively investigated for lung gene therapy of Cystic Fibrosis. To avoid precipitation of the lipoplexes at the high concentrations required for efficient transfection of the airway epithelium in vivo, we have developed novel systems involving polyethyleneglycol (PEG) conjugates. Incorporation of adequate PEG derivatives allowed to prepare colloidally stable concentrated lipoplexes when using the cationic lipid bis-guanidinium-tren-cholesterol (BGTC). Most importantly, intranasal instillation of pegylated BGTC/DOPE lipoplexes led to improved transfection of the mouse airways. Pegylation of KanaChol/DOPE lipoplexes formed by KanaChol, a novel cholesterol derivative characterized by an aminoglycoside (kanamycin) polar headgroup, also permitted efficient transfection of the mouse airways.