A placebo-controlled study of liposome-mediated gene transfer to the nasal epithelium of patients with cystic fibrosis

• Published in: Gene therapy Vol. 4; no. 3; pp. 199 - 209
• Main Authors: GILL, D. R, SOUTHERN, K. W, LANE, D. J, LITTLEWOOD, J. M, WEBB, A. K, MIDDLETON, P. G, COLLEDGE, W. H, CUTHBERT, A. W, EVANS, M. J, HIGGINS, C. F, HYDE, S. C, MOFFORD, K. A, SEDDON, T, HUANG, L, SORGI, F, THOMSON, A, MACVINISH, L. J, RATCLIFF, R, BILTON, D
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-03-1997
• Subjects: Adolescent; Adult; Biological and medical sciences; Biopsy; CF gene; Chloride transport; Chlorides - metabolism; Cystic fibrosis; Cystic Fibrosis - metabolism; Cystic Fibrosis - therapy; Cystic fibrosis transmembrane conductance regulator; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; DNA, Complementary; Dosage; Double-Blind Method; Electrophysiology; Epithelial cells; Epithelium; Epithelium - metabolism; Epithelium - physiopathology; Female; Fluorescence microscopy; Gastroenterology. Liver. Pancreas. Abdomen; Gene transfer; Gene Transfer Techniques; Hereditary diseases; Humans; Ion Transport; Liposomes; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Lung diseases; Male; Medical sciences; Microscopy, Fluorescence; Nasal Mucosa - metabolism; Nasal Mucosa - physiopathology; Other diseases. Semiology; Patients; Placebos; Human; Respiratory disease; Electrophysiology; Liposome; Cystic fibrosis; Epithelium; Genetic disease; Genetic transfer; Plasmid; Complementary DNA; Gene; Nose; Digestive diseases; Clinical trial; Cystic fibrosis transmembrane conductance regulator; Gene therapy; Vector; Pancreatic disease
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3300391

Cystic fibrosis (CF) is a common, serious, inherited disease. The major cause of mortality in CF is lung disease, due to the failure of airway epithelial cells to express a functional product of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. A potential treatment for CF lung disease is the expression of CFTR in the airways following gene transfer. We have undertaken a double-blinded, placebo-controlled, clinical study of the transfer of the CFTR cDNA to the nasal epithelium of 12 CF patients. Cationic liposomes complexed with plasmid containing the human CFTR cDNA were administered to eight patients, whilst four patients received placebo. Biopsies of the nasal epithelium taken 7 days after dosing were normal. No significant changes in clinical parameters were observed. Functional expression of CFTR assessed by in vivo nasal potential difference measurements showed transient correction of the CF chloride transport abnormality in two patients (15 days after dosing in one patient). Fluorescence microscopy demonstrated CFTR function ex vivo. In cells from nasal brushings. In total, evidence of functional CFTR gene transfer was obtained in six out of the eight treated patients. These results provide proof of concept for liposome-mediated CF gene transfer.