학술논문
Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease
Document Type
Academic Journal
Author
Malech, Harry L.; Maples, Phillip B.; Whiting-Theobald, Narda; Linton, Gilda F.; Sekhsaria, Sudhir; Vowells, Sarah J.; Li, Fei; Miller, Judi A.; DeCarlo, Ellen; Holland, Steven M.; Leitman, Susan F.; Carter, Charles S.; Butz, Robert E.; Read, Elizabeth J.; Fleisher, Thomas A.; Schneiderman, Richard D.; Van Epps, Dennis E.; Spratt, S. Kaye; Maack, Christopher A.; Rokovich, Joseph A.; Cohen, Lawrence K.; Gallin, John I.
Source
Proceedings of the National Academy of Sciences of the United States. Oct 28, 1997, Vol. 94 Issue 22, p12133, 6 p. photograph
Subject
Language
ISSN
0027-8424
Abstract
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.sup.phox] deficiency form of chronic granulomatous disease received intravenous infusions of autologous [CD34.sup.+] peripheral blood stem cells (PBSCs) that had been transduced ex vivo with a recombinant retrovirus encoding normal [p47.sup.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.