RETROVIRAL TRANSFER AND EXPRESSION OF THE HUMAN MULTIPLE-DRUG RESISTANCE (MDR) GENE IN PERIPHERAL-BLOOD PROGENITOR CELLS

The multiple drug resistance (MDR) gene P-glycoprotein product is a tr ansmembrane efflux pump that prevents toxicity of a variety of chemoth erapeutic agents, including the anthracyclines, Vinca alkaloids, podop hyllins, and taxol. The bone marrow toxicity of these drugs is due to the low or absent expression of MDR in marrow cells, Transfer and expr ession of the human MDR gene into bone marrow progenitors should preve nt this toxicity, We report here the efficient transfer and expression of the MDR gene by retroviral-mediated gene transfer into CD34(+) cel ls isolated from peripheral blood progenitor cells (PBPCs), comparable to that obtained using bone marrow-derived progenitors, Optimal MDR t ransduction of these PBPC-derived cells requires exposure to growth fa ctors and a period of preincubation, In addition, we demonstrate that we can transduce up to 100% of progenitor cells derived from PBPCs and can protect up to 25% of these progenitors from a dose of taxol toxic to untransduced controls.