[Prospects of gene therapy in mucoviscidosis using viral infection of the airway epithelium].
Mucoviscidosis is the most common severe inherited autosomal recessive disease. Since the gene has been recognised (cystic fibrosis transmembrane conductance regulator gene) (CFTR) the technique of genetic transfer has been applied to the airway epithelium. The prospect for gene therapy to treat the consequences of bronchopulmonary mucoviscidosis is now evident. The in vitro introduction of the normal CFTR human gene in epithelial cells has been obtained using recombinant retrovirus, adenovirus and parvovirus rendered defective for replication. The abnormal bioelectric phenotype of the cells from patients with mucoviscidosis has been corrected. Of these, only adenovirus and parvovirus have been capable of assuring effective genetic transfer by direct introduction into the airways. This data has been considered sufficient to justify starting clinical trials in man with adenovirus; the preliminary results confirm the possibility of correcting the chloride transport. Nevertheless the observation of an immune response and secondary inflammation raises ethical questions relative to the safety of such trials. This observation justifies research into an alternative non-viral technique such as employing liposomes. The authors have made a review of the data which may be established as a basis for genetic therapy for mucoviscidosis.
Bayle
J Y
JY
Service de Pneumologie, Hôpital de la Croix-Rousse, Lyon.
Boucher
R C
RC
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels; D003550:Cystic Fibrosis / Q000235:genetics / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004267:DNA Viruses / Q000235:genetics; D004848:Epithelium / Q000382:microbiology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010321:Parvoviridae / Q000235:genetics; D012137:Respiratory System / Q000382:microbiology; D012190:Retroviridae / Q000235:genetics; D014162:Transfection
C505032:CFTR protein, human; D018118:Chloride Channels; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator