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

B. A. Bunnell, K. A. Kluge, S. Q. Lee-Lin, E. R. Byrne, D. Orlic, M. E. Metzger, B. A. Agricola, R. P. Wersto, D. M. Bodine, R. A. Morgan, R. E. Donahue

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13 Scopus citations

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 50,000/μl and whose leukocyte counts had recovered by days 8 and 10 after having received 1.7 x 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.

Original languageEnglish
Pages (from-to)48-56
Number of pages9
JournalGene Therapy
Volume6
Issue number1
DOIs
StatePublished - Jan 1999

Keywords

  • Hematopoietic cells
  • Restricted expression
  • Retroviral vector
  • Retrovirus receptor

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    Bunnell, B. A., Kluge, K. A., Lee-Lin, S. Q., Byrne, E. R., Orlic, D., Metzger, M. E., Agricola, B. A., Wersto, R. P., Bodine, D. M., Morgan, R. A., & Donahue, R. E. (1999). 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, 6(1), 48-56. https://doi.org/10.1038/sj.gt.3300808