title: A placebo-controlled study of liposome-mediated gene transfer to the nasal epithelium of patients with cystic fibrosis.
abstract: 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.
authors.affiliation: Nuffield Department of Clinical Biochemistry, University of Oxford, John Radcliffe Hospital, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Gill
authors.forename: K W
authors.initials: KW
authors.lastname: Southern
authors.forename: K A
authors.initials: KA
authors.lastname: Mofford
authors.forename: T
authors.initials: T
authors.lastname: Seddon
authors.forename: L
authors.initials: L
authors.lastname: Huang
authors.forename: F
authors.initials: F
authors.lastname: Sorgi
authors.forename: A
authors.initials: A
authors.lastname: Thomson
authors.forename: L J
authors.initials: LJ
authors.lastname: MacVinish
authors.forename: R
authors.initials: R
authors.lastname: Ratcliff
authors.forename: D
authors.initials: D
authors.lastname: Bilton
authors.forename: D J
authors.initials: DJ
authors.lastname: Lane
authors.forename: J M
authors.initials: JM
authors.lastname: Littlewood
authors.forename: A K
authors.initials: AK
authors.lastname: Webb
authors.forename: P G
authors.initials: PG
authors.lastname: Middleton
authors.forename: W H
authors.initials: WH
authors.lastname: Colledge
authors.forename: A W
authors.initials: AW
authors.lastname: Cuthbert
authors.forename: M J
authors.initials: MJ
authors.lastname: Evans
authors.forename: C F
authors.initials: CF
authors.lastname: Higgins
authors.forename: S C
authors.initials: SC
authors.lastname: Hyde
mesh_terms: D000293:Adolescent; D000328:Adult; D002712:Chlorides / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary; D004311:Double-Blind Method; D004594:Electrophysiology; D004848:Epithelium / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D017136:Ion Transport; D008081:Liposomes; D008297:Male; D008856:Microscopy, Fluorescence; D009297:Nasal Mucosa / Q000378:metabolism / Q000503:physiopathology
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D018076:DNA, Complementary; D008081:Liposomes; D019005:Cystic Fibrosis Transmembrane Conductance Regulator