title: Chronic granulomatous disease: towards gene therapy.
abstract: Failure of a superoxide generating system, the NADPH oxidase, present in neutrophils and other phagocytes gives rise to chronic granulomatous disease (CGD), a group of single gene inherited disorders all characterised by an extreme susceptibility to pyogenic infection, with potentially fatal consequences. About 30% of CGD cases are due to an autosomally inherited deficiency of a 47 kDa cytoplasmic component of the oxidase (p47-phox). Epstein-Barr virus (EBV) immortalised B-lymphocyte lines established from these CGD patients also express this NADPH oxidase defect and consequently are rendered incapable of generating superoxide on stimulation. We have utilised a p47-phox-deficient EBV-transformed B cell line as a recipient for retroviral transfer of a functional p47-phox cDNA. The presence and activity of the retrovirally encoded p47-phox in the transduced cells is demonstrated and we show that this restores their capacity to generate superoxide.
authors.affiliation: Department of Medicine, Rayne Institute, University College London.
authors.forename: A
authors.initials: A
authors.lastname: Thrasher
authors.forename: A
authors.initials: A
authors.lastname: Segal
authors.forename: C
authors.initials: C
authors.lastname: Casimir
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D002472:Cell Transformation, Viral; D005808:Genes, Recessive; D015316:Genetic Therapy; D005822:Genetic Vectors; D006105:Granulomatous Disease, Chronic / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D008163:Luminescent Measurements; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics; D009252:NADPH Dehydrogenase / Q000235:genetics; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D013481:Superoxides / Q000378:metabolism
chemical_list: D010750:Phosphoproteins; D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D009252:NADPH Dehydrogenase