Efficient retrovirus-mediated transfer of the multidrug resistance 1 gene into autologous human long-term repopulating hematopoietic stem cells

Rafat Abonour, David A. Williams, Lawrence Einhorn, Kristin M. Hall, Jun Chen, John Coffman, Christie Orschell, Arthur Bank, Ikunoshin Kato, Maureen Ward, Stephen D. Williams, Robert Hromas, Michael Robertson, Franklin O. Smith, David Woo, Bonnie Mills, Edward Srour, Kenneth Cornetta

Research output: Contribution to journalArticle

237 Citations (Scopus)

Abstract

Pre-clinical studies indicate that efficient retrovirus-mediated gene transfer into hematopoietic stem cells and progenitor cells can be achieved by co-localizing retroviral particles and target cells on specific adhesion domains of fibronectin. In this pilot study, we used this technique to transfer the human multidrug resistance 1 gene into stem and progenitor cells of patients with germ cell tumors undergoing autologous transplantation. There was efficient gene transfer into stem and progenitor cells in the presence of recombinant fibronectin fragment CH-296. The infusion of these cells was associated with no harmful effects and led to prompt hematopoietic recovery. There was in vivo vector expression, but it may have been limited by the high rate of aberrant splicing of the multidrug resistance 1 gene in the vector. Gene marking has persisted more than a year at levels higher than previously reported in humans.

Original languageEnglish
Pages (from-to)652-658
Number of pages7
JournalNature Medicine
Volume6
Issue number6
DOIs
StatePublished - Jun 2000

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MDR Genes
Retroviridae
Hematopoietic Stem Cells
Stem cells
Gene transfer
Stem Cells
Genes
Fibronectins
Cells
Tumors
Adhesion
Autologous Transplantation
Germ Cell and Embryonal Neoplasms
Recovery

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Efficient retrovirus-mediated transfer of the multidrug resistance 1 gene into autologous human long-term repopulating hematopoietic stem cells. / Abonour, Rafat; Williams, David A.; Einhorn, Lawrence; Hall, Kristin M.; Chen, Jun; Coffman, John; Orschell, Christie; Bank, Arthur; Kato, Ikunoshin; Ward, Maureen; Williams, Stephen D.; Hromas, Robert; Robertson, Michael; Smith, Franklin O.; Woo, David; Mills, Bonnie; Srour, Edward; Cornetta, Kenneth.

In: Nature Medicine, Vol. 6, No. 6, 06.2000, p. 652-658.

Research output: Contribution to journalArticle

Abonour, Rafat ; Williams, David A. ; Einhorn, Lawrence ; Hall, Kristin M. ; Chen, Jun ; Coffman, John ; Orschell, Christie ; Bank, Arthur ; Kato, Ikunoshin ; Ward, Maureen ; Williams, Stephen D. ; Hromas, Robert ; Robertson, Michael ; Smith, Franklin O. ; Woo, David ; Mills, Bonnie ; Srour, Edward ; Cornetta, Kenneth. / Efficient retrovirus-mediated transfer of the multidrug resistance 1 gene into autologous human long-term repopulating hematopoietic stem cells. In: Nature Medicine. 2000 ; Vol. 6, No. 6. pp. 652-658.
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AU - Coffman, John

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AU - Bank, Arthur

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