Pharmacologically regulated in vivo selection in a large animal.

نویسندگان

  • Tobias Neff
  • Peter A Horn
  • Victor E Valli
  • Allen M Gown
  • Scott Wardwell
  • Brent L Wood
  • Christof von Kalle
  • Manfred Schmidt
  • Laura J Peterson
  • Julia C Morris
  • Robert E Richard
  • Tim Clackson
  • Hans-Peter Kiem
  • C Anthony Blau
چکیده

The inefficiency of gene transfer has greatly hindered gene therapy. In vivo selection may increase the frequency of genetically modified cells, thereby circumventing this critical limitation. Here we demonstrate regulated in vivo selection in a large animal. CD34(+) cells from 2 dogs were engineered to express a conditional derivative of the thrombopoietin receptor (F36Vmpl). Activation of the receptor through administration of a dimerizing drug, AP20187, produced reversible, drug-dependent rises in genetically modified red cells, white cells, and platelets in both animals, with minimal side effects. Cell growth switches could greatly enhance the efficacy and applicability of gene and cell therapy.

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عنوان ژورنال:
  • Blood

دوره 100 6  شماره 

صفحات  -

تاریخ انتشار 2002