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A placebo-controlled study of liposome-mediated gene transfer to the nasal epithelium of patients with cystic fibrosis.
Gene Ther 1997; 4(3):199-209GT

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+Show Affiliations

Nuffield Department of Clinical Biochemistry, University of Oxford, John Radcliffe Hospital, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9135733

Citation

Gill, D R., et al. "A Placebo-controlled Study of Liposome-mediated Gene Transfer to the Nasal Epithelium of Patients With Cystic Fibrosis." Gene Therapy, vol. 4, no. 3, 1997, pp. 199-209.
Gill DR, Southern KW, Mofford KA, et al. A placebo-controlled study of liposome-mediated gene transfer to the nasal epithelium of patients with cystic fibrosis. Gene Ther. 1997;4(3):199-209.
Gill, D. R., Southern, K. W., Mofford, K. A., Seddon, T., Huang, L., Sorgi, F., ... Hyde, S. C. (1997). A placebo-controlled study of liposome-mediated gene transfer to the nasal epithelium of patients with cystic fibrosis. Gene Therapy, 4(3), pp. 199-209.
Gill DR, et al. A Placebo-controlled Study of Liposome-mediated Gene Transfer to the Nasal Epithelium of Patients With Cystic Fibrosis. Gene Ther. 1997;4(3):199-209. PubMed PMID: 9135733.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A placebo-controlled study of liposome-mediated gene transfer to the nasal epithelium of patients with cystic fibrosis. AU - Gill,D R, AU - Southern,K W, AU - Mofford,K A, AU - Seddon,T, AU - Huang,L, AU - Sorgi,F, AU - Thomson,A, AU - MacVinish,L J, AU - Ratcliff,R, AU - Bilton,D, AU - Lane,D J, AU - Littlewood,J M, AU - Webb,A K, AU - Middleton,P G, AU - Colledge,W H, AU - Cuthbert,A W, AU - Evans,M J, AU - Higgins,C F, AU - Hyde,S C, PY - 1997/3/1/pubmed PY - 1997/3/1/medline PY - 1997/3/1/entrez SP - 199 EP - 209 JF - Gene therapy JO - Gene Ther. VL - 4 IS - 3 N2 - 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. SN - 0969-7128 UR - https://www.unboundmedicine.com/medline/citation/9135733/A_placebo_controlled_study_of_liposome_mediated_gene_transfer_to_the_nasal_epithelium_of_patients_with_cystic_fibrosis_ L2 - http://dx.doi.org/10.1038/sj.gt.3300391 DB - PRIME DP - Unbound Medicine ER -