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

Citation
Ba. Bunnell 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(1), 1999, pp. 48-56
Citations number
11
Categorie Soggetti
Molecular Biology & Genetics
Journal title
GENE THERAPY
ISSN journal
09697128 → ACNP
Volume
6
Issue
1
Year of publication
1999
Pages
48 - 56
Database
ISI
SICI code
0969-7128(199901)6:1<48:TOTNPC>2.0.ZU;2-4
Abstract
The transduction efficiencies of immunoselected rhesus macaque (Macaca mula tta) CD34(+) cells and colony-forming progenitor cells based on polymerase chain reaction (PCR) analysis were comparable for an amphotropic Moloney mu rine leukemia virus (MLV) retroviral vector and a retroviral vector derived from the gibbon ape leukemia virus (GaLV) packaging cell line, PG13. On pe rforming autologous transplantation studies using immunoselected CD34(+) ce lls transduced with the GaLV envelope (env) retroviral vector, less than 1% of peripheral blood (PB) contained provirus. This was true whether bone ma rrow (BM) or cytokine-mobilized PB immunoselected CD34(+) cells were reinfu sed. This level of marking was evident in two animals whose platelet counts never fell below 50 000/mu l and whose leukocyte counts had recovered by d ays 8 and 10 after having received 1.7 x 10(7) or greater of cytokine-mobil ized CD34(+) PB cells/kg. Reverse transcriptase(RT)PCR analysis of CD34(+) subsets for both the GaLV and amphotropic receptor were performed. The expr ession of the GaLV receptor was determined to be restricted to CD34(+) Thy- 1(+) cells, and both CD34(+) CD38(+) and CD34(+) CD38dim cells, while the a mphotropic receptor was present on all CD34(+) cell subsets examined. Our f indings suggest that, in rhesus macaques, PG13-derived retroviral vectors m ay only be able to transduce a subset of CD34(+) cells as only CD34(+) Thy- 1(+) cells express the GaLV receptor.