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      Improved short-term engraftment of lentivirally versus gammaretrovirally transduced allogeneic canine repopulating cells.

        1 , , ,
      The journal of gene medicine
      Wiley

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          Abstract

          Gammaretroviral vectors require cell division for efficient transduction. Thus, extended cell culture times are necessary for efficient transduction with gammaretroviral vectors, which in turn can lead to stem cell loss and impaired engraftment. Lentiviral vectors transduce nondividing cells and are therefore able to transduce stem cells in short transduction protocols. Here, we compared the short-term engraftment of lentivirally and gammaretrovirally transduced canine allogeneic DLA-matched littermate cells. A reduced conditioning regimen of 400 cGy total body irradiation was used in preparation for clinical studies. Two dogs received a graft of gammaretrovirally transduced CD34-selected cells. CD34(+) cells were prestimulated for 30 h and then exposed twice to concentrated RD114 pseudotype vector. Three dogs received lentivirally transduced CD34-selected cells. Cells were transduced overnight with concentrated VSV-G pseudotype lentiviral vector. The animals in the lentiviral group showed a significantly faster granulocyte recovery. VNTR analysis 40-50 days after transplantation revealed higher donor chimerism for the lentiviral group compared to the retroviral group. These data suggest that short lentiviral transduction protocols may be superior to extended gammaretroviral transduction protocols with respect to engraftment potential of transduced CD34(+) hematopoietic repopulating cells.

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          Author and article information

          Journal
          J Gene Med
          The journal of gene medicine
          Wiley
          1099-498X
          1099-498X
          May 2007
          : 9
          : 5
          Affiliations
          [1 ] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
          Article
          10.1002/jgm.1033
          17421055
          5f2553f4-1984-4fa1-9d9d-140b2d5a7896
          Copyright (c) 2007 John Wiley & Sons, Ltd.
          History

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