Selection of drug-resistant bone marrow cells in vivo after retroviral transfer of human MDR1.

Sorrentino BP, Brandt SJ, Bodine D, Gottesman M, Pastan I, Cline A, Nienhuis AW
Science. 1992 257 (5066): 99-103

PMID: 1352414 · DOI:10.1126/science.1352414

Experiments were performed to determine if retroviral-mediated transfer of the human multidrug resistance 1 gene (MDR1) into murine bone marrow cells would confer drug resistance to the cells and whether the MDR1 gene could be used as a dominant selectable marker in vivo. When mice transplanted with bone marrow cells containing a transferred MDR1 gene were treated with the cytotoxic drug taxol, a substantial enrichment for transduced bone marrow cells was observed. This demonstration of positive selection establishes the ability to amplify clones of transduced hematopoietic cells in vivo and suggests possible applications in human therapy.

MeSH Terms (18)

Alkaloids Antineoplastic Agents, Phytogenic Base Sequence Bone Marrow Bone Marrow Transplantation DNA Drug Resistance Erythrocytes Genetic Vectors Hematopoietic Stem Cells Humans Molecular Sequence Data Oligodeoxyribonucleotides Paclitaxel Polymerase Chain Reaction Proviruses Retroviridae Transfection

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