Safety and biological efficacy of a lipid-CFTR complex for gene transfer in the nasal epithelium of adult patients with cystic fibrosis (2000)

Noone, P. G., Hohneker, K. W., Zhou, Z., Johnson, L. G., Foy, C., Gipson, C., Jones, K., Noah, T. L., Leigh, M. W., Schwartzbach, C., Efthimiou, J., Pearlman, R., Boucher, R. C. & Knowles, M. R.

Mol Ther, 1, 105-114

Pubmed     Back

Gene transfer is an attractive option to treat the basic defect in cystic fibrosis. In a double-blind, placebo-controlled, rising-dose tolerance study in the nasal epithelium, we tested the safety and efficacy of a cationic liposome [p-ethyl-dimyristoylphosphadityl choline (EDMPC) cholesterol] complexed with an expression plasmid containing hCFTR cDNA. Eleven adult CF patients were studied in a protocol that allowed comparisons within individual subjects: vector and placebo were sprayed into alternate nostrils at intervals over 7 h. After dosing, vector-specific DNA was present in nasal lavage of all subjects for up to 10 days. There were no adverse events. The vector-treated epithelium did not exhibit a significant increase in CFTR-mediated Cl- conductance from baseline and was not different from the placebo-treated nostril: mean deltaCFTR Cl- conductance, mV +/- SEM, -1.6+/-0.4 vs -0.6+/-0.4, respectively. CFTR-mediated Cl- conductance increased toward normal during repetitive nasal potential difference measurements over the 3 days before dosing which influenced the postdosing calculations. No vector-specific mRNA was detected in the nasal epithelial scrape biopsies, although endogenous CFTR mRNA was detected in all subjects. We conclude that the lipid-DNA complex is safe, but did not produce consistent evidence of gene transfer to the nasal epithelium by physiologic or molecular measures.

Introductory Videos
Medical Futures Innovation Award 2011
Twitter Feed
About Us
Contact Us
Lab Events
Environemental Policy
About this Site

Google Site Search

Site Feedback Form

All Site Images



How the Consortium works/FAQs

Consortium Website

Centre for Molecular Medicine, Edinburgh
The Roslin Institute
Dep of Gene Therapy, Imperial



The Run-in Study

Single Dose Clinical Trial

Multi Dose Clinical Trial


Our Research

Non-viral Vector Development

Aerosol Mediated Gene Delivery

Viral Vector Development

Taqman Core Facility

Cystic Fibrosis

History of CF

Discovery of the CFTR Gene

CFTR Protein Structure

CFTR Function

CF Links


Gene Therapy

Introduction to Gene Therapy

Other CF Gene Therapy Groups

Why use Gene Therapy for CF

Target Cells for CF Gene Therapy

Barriers for CF Gene Therapy

Clinical Trials

Gene Therapy Successes

Gene Therapy Links




Papers in Journals

Conference Posters & Presentations

Book Chapters

D.Phil Theses



Gene Therapy Seminars


Directions & Venue