Molecular Therapy
Volume 1, Issue 1, January 2000, Pages 105-114
Journal home page for Molecular Therapy

Trial
Safety and Biological Efficacy of a Lipid–CFTR Complex for Gene Transfer in the Nasal Epithelium of Adult Patients with Cystic Fibrosis*

https://doi.org/10.1006/mthe.1999.0009Get rights and content
Under a Creative Commons license
open archive

Abstract

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 ΔCFTR 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.

Keywords

liposome
gene transfer
cystic fibrosis
CFTR
EDMPC

Cited by (0)

*

This study was supported in part by grants from the National Institutes of Health (NIH 34322, RR0046), the Cystic Fibrosis Foundation (CFF L543), and a grant from Glaxo-Wellcome Inc.