Progress in gene therapy for chronic granulomatous disease

Progress in development of gene therapy for chronic granulomatous disease ( CGD), an inherited defect in leukocyte oxidase deficiency, is reviewed. The use of retrovirus vectors to transfer oxidase enzyme subunit cDNA sequence into hematopoietic progenitors results in correction of oxidase activity i n neutrophils differentiating from transduced progenitors. In CGD mouse kno ckouts (X-linked gp91phox-deficient CGD and autosomal recessive p47phox-def icient CGD), gene therapy correction of the CGD defect resulted in appearan ce of oxidase-normal neutrophils in the peripheral blood and increased host resistance to challenge with fungi or bacteria. In a phase I clinical tria l of ex vivo gene therapy of p47phox-deficient CGD, prolonged production (2 -6 months) of a low number (1:5000) of oxidase-normal neutrophils was achie ved. This therapy might prove beneficial in a setting of prolonged infectio n in CGD patients, in which even transient production of autologous gene-co rrected neutrophils might augment host defense.