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 M. Traycoff, Arthur Bank, Ikunoshin Kato, Maureen Ward, Stephen D. Williams, Robert Hromas, Michael J. Robertson, Franklin O. Smith, David Woo, Bonnie Mills, Edward F. Srour, Kenneth Cornetta

Research output: Contribution to journalArticle

239 Scopus citations

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 (US)
Pages (from-to)652-658
Number of pages7
JournalNature Medicine
Volume6
Issue number6
DOIs
StatePublished - Jun 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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