Previous clinical studies of ex vivo gene therapy for chronic granulomatous disease (CGD) without marrow conditioning have resulting in transient correction of the oxidase defect in over 0.1% of circulation neutrophils. Use of improved RD114 envelope pseudotyped vectors capable of transducing >95% of CD34+ stem cells ex vivo, together with non-ablative marrow conditioning will be incorporated into the next generation of clinical trials of ex vivo gene therapy for CGD. These maneuvers might result in clinical benefit to CGD patients from gene therapy.