Gene therapy of chronic granulomatous disease.

Abstract

Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder which results from absence or malfunction of the respiratory burst oxidase normally expressed in neutrophils and other phagocytic leukocytes. Two-thirds of the patients are males hemizygous for mutations in the X-linked gene coding for gp91-phox. As a therapeutic approach towards the X-linked form of CGD bicistronic retroviral vectors containing the gp91-phox gene and a selectable marker gene were constructed. The ability of these vectors to restore NADPH oxidase activity was tested in a human myeloid leukemic cell line that is defective in superoxide production, as well as in primary CD34+ cells obtained from X-CGD patients. Under optimal conditions 80% of the CD34+ cells derived from bone marrow of one X-CGD patient were transduced. The level of superoxide production, in phagocytes derived from transduced cells was 68.9% of normal levels. Considering that low levels of superoxide generating activity are sufficient for normal host defense, the present experiments provide the basis for the development of a gene replacement therapy for the X-linked form of CGD.

• Authors: M Grez, S Becker, S Saulnier, H Knöss, M G Ott, A Maurer, M C Dinauer, D Hoelzer, R Seger, J P Hossle
• Journal: Bone marrow transplantation (Bone Marrow Transplant) Vol. 25 Suppl 2 Pg. S99-104 (May 2000) ISSN: 0268-3369 [Print] England
• PMID: 10933200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD34
• DNA, Complementary
• Membrane Glycoproteins
• Superoxides
• CYBB protein, human
• NADPH Oxidase 2
• NADPH Oxidases

Topics

• Animals
• Antigens, CD34 (metabolism)
• Bone Marrow Cells (immunology, metabolism, virology)
• Bone Marrow Transplantation
• Cell Line
• DNA, Complementary (genetics)
• Gene Expression
• Genetic Therapy (methods)
• Genetic Vectors
• Granulomatous Disease, Chronic (genetics, metabolism, therapy)
• Humans
• Male
• Membrane Glycoproteins (genetics)
• Mice
• NADPH Oxidase 2
• NADPH Oxidases (genetics)
• Respiratory Burst
• Retroviridae (genetics)
• Superoxides (metabolism)
• Transduction, Genetic
• X Chromosome (genetics)