Retroviral-mediated gene transfer and nonmyeloablative conditioning

Studies in a murine X-linked chronic granulomatous disease model

W. Goebel, Mary C. Dinauer

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Our laboratory has reported the correction of neutrophil NADPH oxidase function by retroviral-mediated gene transfer (RMGT) in murine X-linked chronic granulomatous disease (X-CGD). Few studies, however, have used nonmyeloablative conditioning in conjunction with RMGT. Promising methods of decreased intensity conditioning include low dose irradiation and antimetabolite conditioning. Preliminary studies using syngeneic mice transplanted with fresh marrow cells indicate that high levels of donor cell chimerism can be achieved with low-dose radiation or 5-fluorouracil-based conditioning regimens. Early data from experiments in which low-dose radiation-conditioned X-CGD recipients were transplanted with retrovirus-transduced X-CGD marrow cells show that gene-corrected neutrophils can be detected by NBT assay for NADPH oxidase activity reconstitution 4 months posttransplant, although these levels are much lower than the 50%-70% gene-corrected cell detected in lethally irradiated recipients. Transplantation of retrovirus-transduced marrow cells into 5-fluorouracil conditioned hosts is also being explored.

Original languageEnglish
Pages (from-to)787-790
Number of pages4
JournalJournal of Pediatric Hematology/Oncology
Volume24
Issue number9
DOIs
StatePublished - Dec 2002

Fingerprint

Chronic Granulomatous Disease
NADPH Oxidase
Genes
Bone Marrow
Retroviridae
Fluorouracil
Neutrophils
Radiation
Antimetabolites
Chimerism
Transplantation

Keywords

  • Chronic granulomatous disease
  • Gene therapy
  • Granuloma formation
  • Neutrophils
  • Nonmyeloablative conditioning Cutaneous inflammation
  • Retrovirus

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Oncology
  • Hematology

Cite this

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