Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease.
نویسندگان
چکیده
Little is known about the potential for engraftment of autologous hematopoietic stem cells in human adults not subjected to myeloablative conditioning regimens. Five adult patients with the p47(phox) deficiency form of chronic granulomatous disease received intravenous infusions of autologous CD34(+) peripheral blood stem cells (PBSCs) that had been transduced ex vivo with a recombinant retrovirus encoding normal p47(phox). Although marrow conditioning was not given, functionally corrected granulocytes were detectable in peripheral blood of all five patients. Peak correction occurred 3-6 weeks after infusion and ranged from 0.004 to 0.05% of total peripheral blood granulocytes. Corrected cells were detectable for as long as 6 months after infusion in some individuals. Thus, prolonged engraftment of autologous PBSCs and continued expression of the transduced gene can occur in adults without conditioning. This trial also piloted the use of animal protein-free medium and a blood-bank-compatible closed system of gas-permeable plastic containers for culture and transduction of the PBSCs. These features enhance the safety of PBSCs directed gene therapy.
منابع مشابه
Chronic granulomatous disease due to granulocytes with abnormal NADPH oxidase activity and deficient cytochrome-b.
A patient with an X-linked genetic disease resembling chronic granulomatous disease (CGD) but differing in several aspects from previously studied cases is described. The oxidase enzyme of the patient's granulocytes was normally activated, but had reduced activity as shown by an increased Michaelis constant and decreased maximum velocity of NADPH-dependent superoxide production. Cytochrome-b wa...
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عنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 94 22 شماره
صفحات -
تاریخ انتشار 1997