Gene Transfer by Guanidinium-Cholesterol Cationic Lipids into Airway Epithelial Cells in vitro and in vivo

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 5; pp. 1651 - 1656
• Main Authors: Oudrhiri, Noufissa, Vigneron, Jean-Pierre, Peuchmaur, Michel, Leclerc, Tony, Lehn, Jean-Marie, Lehn, Pierre
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 04.03.1997; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: Adenoviridae - genetics; Animals; Antibodies; beta-Galactosidase - genetics; beta-Galactosidase - metabolism; Biological Sciences; Biology; Cell culture techniques; Cell lines; Cells, Cultured; Cellular immunity; Cholesterol - analogs & derivatives; Cultured cells; Cystic Fibrosis - therapy; Epithelial cells; Epithelium; Epithelium - metabolism; Escherichia coli - enzymology; Gene Transfer Techniques; Genes; Genes, Reporter - genetics; Genetic Therapy; Genetic Vectors; Guanidines; Humans; Lipids; Liposomes - administration & dosage; Luciferases - genetics; Luciferases - metabolism; Lungs; Male; Membranes; Mice; Nasal Polyps - metabolism; Phosphatidylethanolamines; Plasmids; Trachea - metabolism; Transfection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.5.1651

Synthetic vectors represent an attractive alternative approach to viral vectors for gene transfer, in particular into airway epithelial cells for lung-directed gene therapy for cystic fibrosis. Having recently found that guanidinium-cholesterol cationic lipids are efficient reagents for gene transfer into mammalian cell lines in vitro, we have investigated their use for gene delivery into primary airway epithelial cells in vitro and in vivo. The results obtained indicate that the lipid bis (guanidinium)-tren-cholesterol (BGTC) can be used to transfer a reporter gene into primary human airway epithelial cells in culture. Furthermore, liposomes composed of BGTC and dioleoyl phosphatidylethanolamine (DOPE) are efficient for gene delivery to the mouse airway epithelium in vivo. Transfected cells were detected both in the surface epithelium and in submucosal glands. In addition, the transfection efficiency of BGTC/DOPE liposomes in vivo was quantitatively assessed by using the luciferase reporter gene system.