Evaluation in vitro and in vivo of cationic liposome-expression construct complexes for cystic fibrosis gene therapy

G McLachlan; D J Davidson; B J Stevenson; P Dickinson; H Davidson-Smith; J R Dorin; D J Porteous

Evaluation in vitro and in vivo of cationic liposome-expression construct complexes for cystic fibrosis gene therapy

Gene Ther. 1995 Nov;2(9):614-22.

Authors

G McLachlan¹, D J Davidson, B J Stevenson, P Dickinson, H Davidson-Smith, J R Dorin, D J Porteous

Affiliation

¹ MRC Human Genetics Unit, Western General Hospital, Edinburgh, Scotland.

PMID: 8548550

Abstract

We have tested the cationic liposome N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethyl-ammoniummethylsul phate, (DOTAP), for gene delivery in vitro and in vivo with a view to clinical use in gene therapy for cystic fibrosis. Delivery of lacZ cDNA-DOTAP complexes via aerosol showed promoter-dependent differences in the pattern and longevity of expression. Repeated administration was well tolerated. The potential for the transfer of foreign genes into reproductive tissue was investigated by intravenous injection of DNA-DOTAP into female mice. Foreign DNA was undetectable in the ovaries by Southern blot analysis at 1 and 7 days after injection. Our results suggest that DOTAP merits testing in cystic fibrosis patients for delivery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to the respiratory tract and that substitution of the cytomegalovirus (CMV) promoter for the simian virus (SV) promoter may improve on the transitory response reported previously.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aerosols
Animals
Cell Line
Chlorocebus aethiops
Cystic Fibrosis / therapy*
Cystic Fibrosis Transmembrane Conductance Regulator / biosynthesis
Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
Cystic Fibrosis Transmembrane Conductance Regulator / toxicity
DNA, Recombinant / administration & dosage
DNA, Recombinant / analysis
DNA, Recombinant / genetics
Fatty Acids, Monounsaturated / toxicity
Female
Gene Transfer Techniques*
Genetic Therapy / methods*
Humans
Liposomes*
Lung / chemistry
Lung / physiology
Male
Mice
Ovary / chemistry
Promoter Regions, Genetic
Quaternary Ammonium Compounds / toxicity
Testis / chemistry
beta-Galactosidase / analysis
beta-Galactosidase / biosynthesis
beta-Galactosidase / genetics

Substances

Aerosols
CFTR protein, human
DNA, Recombinant
Fatty Acids, Monounsaturated
Liposomes
Quaternary Ammonium Compounds
Cystic Fibrosis Transmembrane Conductance Regulator
beta-Galactosidase
1,2-dioleoyloxy-3-(trimethylammonium)propane