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

Pre-clinical studies indicate that efficient retrovirus-mediated gene trans fer into hematopoietic stem cells and progenitor cells can be achieved by c o-localizing retroviral particles and target cells on specific adhesion dom ains of fibronectin, In this pilot study, we used this technique to transfe r the human multidrug resistance 1 gene into stem and progenitor cells of p atients 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 recover y. 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 v ector. Gene marking has persisted more than a year at levels higher than pr eviously reported in humans.