title: Gene therapy in a xenograft model of cystic fibrosis lung corrects chloride transport more effectively than the sodium defect.
abstract: We have developed a model of gene therapy for cystic fibrosis (CF) lung disease, based on growth of human CF bronchial xenografts in nu/nu mice. We now report an evaluation of the primary abnormalities in CF lung epithelia--defective Cl secretion and Na hyperabsorption--in xenografts following adenovirus-mediated gene transfer. In vivo infection of CF xenografts with a cystic fibrosis transmembrane regulator (CFTR) recombinant adenovirus, at a multiplicity of infection equal to 100, was sufficient to reconstitute near normal levels of cAMP-stimulated Cl transport, despite transducing only 5% of cells in the pseudostratified epithelium. Correction in sodium hyperabsorption was partial and variable. These experiments define aspects of adenovirus-mediated gene therapy relevant to CF protocols based on intrapulmonary genetic reconstitution.
authors.affiliation: Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Goldman
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: J M
authors.initials: JM
authors.lastname: Wilson
mesh_terms: D000042:Absorption; D017498:Adenovirus E1 Proteins / Q000235:genetics; D000818:Animals; D001692:Biological Transport; D001980:Bronchi / Q000166:cytology / Q000473:pathology; D017690:Cell Transplantation; D002712:Chlorides / Q000378:metabolism; D003550:Cystic Fibrosis / Q000235:genetics* / Q000628:therapy*; D004195:Disease Models, Animal; D004848:Epithelium / Q000502:physiology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D012964:Sodium / Q000378:metabolism / Q000493:pharmacokinetics; D014183:Transplantation, Heterologous / Q000379:methods*
chemical_list: D017498:Adenovirus E1 Proteins; D002712:Chlorides; D012964:Sodium