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Transplantation of transduced nonhuman primate CD34+ cells using a gibbon ape leukemia virus vector: restricted expression of the gibbon ape leukemia virus receptor to a subset of CD34+ cells

Gene Therapy volume 6, pages 48–56 (1999)Cite this article

Abstract

The transduction efficiencies of immunoselected rhesus macaque (Macaca mulatta) CD34+ cells and colony- forming progenitor cells based on polymerase chain reaction (PCR) analysis were comparable for an amphotropic Moloney murine leukemia virus (MLV) retroviral vector and a retroviral vector derived from the gibbon ape leukemia virus (GaLV) packaging cell line, PG13. On performing autologous transplantation studies using immunoselected CD34+ cells transduced with the GaLV envelope (env) retroviral vector, less than 1% of peripheral blood (PB) contained provirus. This was true whether bone marrow (BM) or cytokine-mobilized PB immunoselected CD34+ cells were reinfused. This level of marking was evident in two animals whose platelet counts never fell below 50000/μl and whose leukocyte counts had recovered by days 8 and 10 after having received 1.7 × 107 or greater of cytokine-mobilized CD34+ PB cells/kg. Reverse transcriptase(RT)-PCR analysis of CD34+ subsets for both the GaLV and amphotropic receptor were performed. The expression of the GaLV receptor was determined to be restricted to CD34+ Thy-1+ cells, and both CD34+ CD38+ and CD34+ CD38dim cells, while the amphotropic receptor was present on all CD34+ cell subsets examined. Our findings suggest that, in rhesus macaques, PG13-derived retroviral vectors may only be able to transduce a subset of CD34+ cells as only CD34+Thy-1+ cells express the GaLV receptor.

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Authors and Affiliations

  1. Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

    B A Bunnell & R A Morgan

  2. Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD, USA

    K A Kluge, S-Q Lee-Lin, E R Byrne, M E Metzger, B A Agricola, R P Wersto & R E Donahue

  3. Hematopoiesis Section, Laboratory of Gene Transfer, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

    D Orlic & D M Bodine

  4. Division of Molecular Medicine, Department of Pediatrics, Children’s Hospital Research Foundation, The Ohio State University, Columbus, 43205, Ohio, USA

    B A Bunnell

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Bunnell, B., Kluge, K., Lee-Lin, SQ. et al. Transplantation of transduced nonhuman primate CD34+ cells using a gibbon ape leukemia virus vector: restricted expression of the gibbon ape leukemia virus receptor to a subset of CD34+ cells. Gene Ther 6, 48–56 (1999). https://doi.org/10.1038/sj.gt.3300808

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