Gene therapy of chronic granulomatous disease

M. Grez, S. Becker, S. Saulnier, H. Knöβ, M. G. Ott, A. Maurer, M. C. Dinauer, D. Hoelzer, R. Seger, J. P. Hossle

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish
Pages (from-to)S99-S104
JournalBone Marrow Transplantation
Volume25
DOIs
StatePublished - May 2000

Keywords

  • Cd34+ cells
  • Gene therapy
  • Retroviral vectors
  • X-CGD

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