Abstract
The underlying cause of X-linked chronic granulomatous disease (X-CGD) is mutations in the gp91phox coding gene. Gp91phox is the larger subunit of the cytochrome b558, the membrane-bound terminal redox centre of the respiratory burst oxidase (NADPH oxidase). We have constructed a recombinant adenovirus which contains a functional copy of the human gp91phox cDNA under the control of the cytomegalovirus (CMV) enhancer/promoter region. This vector was used to infect monocyte-derived macrophages of gp91phox-deficient CGD patients. Expression of the gp91phox transgene resulted in ex vivo reconstitution of the respiratory burst activity. Nitroblue-tetrazolium staining indicated that 74% of the patient cells could be phenotypically corrected when compared with a corresponding control culture of normal monocyte-derived macrophages. Adenoviral gene transfer may become a promising tool and gain therapeutical potential by the targeting of autologous monocytes. Genetically corrected autologous monocytes may be used for supportive treatment of X-CGD patients to overcome acute life-threatening infections. Establishment of adenovirus-mediated reconstitution of gp91phox-deficient monocytes therefore represents a first step towards the development of a clinically applicable supportive transient somatic gene therapy in CGD.
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Schneider, S., Rusconi, S., Seger, R. et al. Adenovirus-mediated gene transfer into monocyte-derived macrophages of patients with X-linked chronic granulomatous disease: ex vivo correction of deficient respiratory burst. Gene Ther 4, 524–532 (1997). https://doi.org/10.1038/sj.gt.3300432
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DOI: https://doi.org/10.1038/sj.gt.3300432
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