Efficient retrovirus-mediated transfer of the multidrug resistance 1 gene into autologous human long-term repopulating hematopoietic stem cells
- 1 June 2000
- journal article
- clinical trial
- Published by Springer Nature in Nature Medicine
- Vol. 6 (6) , 652-658
- https://doi.org/10.1038/76225
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.Keywords
This publication has 44 references indexed in Scilit:
- The 30/35 kDa chymotryptic fragment of fibronectin enhances retroviral-mediated gene transfer in purified chronic myelogenous leukemia bone marrow progenitorsLeukemia, 1997
- Results of MDR-1 vector modification trial indicate that granulocyte/macrophage colony-forming unit cells do not contribute to posttransplant hematopoietic recovery following intensive systemic therapyProceedings of the National Academy of Sciences, 1996
- Improved retroviral gene transfer into murine and Rhesus peripheral blood or bone marrow repopulating cells primed in vivo with stem cell factor and granulocyte colony-stimulating factor.Proceedings of the National Academy of Sciences, 1996
- Colocalization of retrovirus and target cells on specific fibronectin fragments increases genetic transduction of mammalian cellsNature Medicine, 1996
- Retroviral Mediated Transfer of the cDNA for Human Glucocerebrosidase into Hematopoietic Stem Cells of Patients with Gaucher Disease. A Phase I Study. National Institutes of Health, Bethesda, MarylandHuman Gene Therapy, 1996
- Maintenance chemotherapy with daily oral etoposide following salvage therapy in patients with germ cell tumors.Journal of Clinical Oncology, 1995
- Bone marrow extracellular matrix molecules improve gene transfer into human hematopoietic cells via retroviral vectors.Journal of Clinical Investigation, 1994
- Improved Methods of Retroviral Vector Transduction and Production for Gene TherapyHuman Gene Therapy, 1994
- Gene marking to determine whether autologous marrow infusion restores long-term haemopoiesis in cancer patientsThe Lancet, 1993
- Expression of a full-length cDNA for the human "MDR1" gene confers resistance to colchicine, doxorubicin, and vinblastine.Proceedings of the National Academy of Sciences, 1987