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

Mol Ther. 2000 Jan;1(1):105-14. doi: 10.1006/mthe.1999.0009.


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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Base Sequence
  • Chlorides / metabolism
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / metabolism
  • Cystic Fibrosis / therapy*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • DNA Primers / genetics
  • DNA, Complementary / administration & dosage
  • DNA, Complementary / genetics
  • Double-Blind Method
  • Electric Conductivity
  • Epithelium / metabolism
  • Female
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Humans
  • Liposomes
  • Male
  • Middle Aged
  • Nasal Mucosa / metabolism
  • Safety


  • CFTR protein, human
  • Chlorides
  • DNA Primers
  • DNA, Complementary
  • Liposomes
  • Cystic Fibrosis Transmembrane Conductance Regulator