RAPID COMMUNICATION CD34+ Peripheral Blood Progenitors as a Target for Genetic Correction of the Two Flavocytochrome bSs8 Defective Forms of Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) can result from any of four single gene defects involving components of the superoxide (0;')-generating phagocyte NADPH oxidase (phox). The phox transmembrane flavocytochrome bsss is composed of two peptides, gpS1Ph" and ~ 2 2 ~ " " . Mutations of gp9lW" cause X-linked CGD, whereas mutations of p22pho" cause one of the three autosomal recessive forms of CGD. We used the Maloney leukemia virus-based MFG retrovirus vector to produce replication defective retroviruses encoding gpSlPh"" or ~ 2 2 ~ ~ " " . To maximize viral titer MFG retroviruses do not contain internal promoter or resistance elements. Epstein-Barr virus transformed B-lymphocyte cell lines (EBV-B) derived from normal individuals contain phox components and produce 0;'. whereas those derived from CGD patients show the CGD defect. Transduction of gp9lPhox or p22Ph""-deficient CGD EBV-B lines resulted in correction of 0," production from a barely detectable