Airway delivery of cationic lipid: DNA complexes for cystic fibrosis.
Cationic lipids are under active consideration as gene delivery vehicles for cystic fibrosis. Initial studies have shown cationic lipids to be effective agents of gene transfer to epithelial cells in vitro. Instillation of these vectors into animal models has led to widely different degrees of transfection of the airway epithelia. Newer generations of cationic lipids, with dramatically improved transfection efficiencies, appear to result in mostly alveolar gene delivery. Aerosol delivery of cationic lipid-DNA complexes has resulted in variable transfection of the airways in animal models. Initial human clinical trials using intranasal instillation have shown variable low levels of expression, accompanied by little toxicity. Recent developments in the formulation of cationic lipid-DNA complexes have resulted in an ability to aerosolize high concentrations of the complex, and should permit an evaluation of the efficacy of these delivery vehicles when aerosolized into cystic fibrosis patients.
Scheule
RK
Gene Transfer Research, Genzyme Research, Genzyme Corporation, 1 Mountain Road, Framingham, MA 01701-9322, USA
Cheng
SH