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

Open Access

1 January 1999

journal article
research article
Published by Springer Nature in Gene Therapy

Vol. 6 (1) , 48-56
https://doi.org/10.1038/sj.gt.3300808

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.

Keywords

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