Gene Therapy (2010) 17, 939–948; doi:10.1038/gt.2010.47; published online 29 April 2010

Large animal models of hematopoietic stem cell gene therapy

G D Trobridge1,2 and H-P Kiem1,2,3

  1. 1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  2. 2Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
  3. 3Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA

Correspondence: Dr H-P Kiem, Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N D1-100, PO Box 19024; Seattle, WA 98109-1024, USA. E-mail:

Received 17 September 2009; Revised 10 December 2009; Accepted 10 December 2009; Published online 29 April 2010.



Large animal models have been instrumental in advancing hematopoietic stem cell (HSC) gene therapy. Here we review the advantages of large animal models, their contributions to the field of HSC gene therapy and recent progress in this field. Several properties of human HSCs including their purification, their cell-cycle characteristics, their response to cytokines and the proliferative demands placed on them after transplantation are more similar in large animal models than in mice. Progress in the development and use of retroviral vectors and ex vivo transduction protocols over the last decade has led to efficient gene transfer in both dogs and nonhuman primates. Importantly, the approaches developed in these models have translated well to the clinic. Large animals continue to be useful to evaluate the efficacy and safety of gene therapy, and dogs with hematopoietic diseases have now been cured by HSC gene therapy. Nonhuman primates allow evaluation of aspects of transplantation as well as disease-specific approaches such as AIDS (acquired immunodeficiency syndrome) gene therapy that can not be modeled well in the dog. Finally, large animal models have been used to evaluate the genotoxicity of viral vectors by comparing integration sites in hematopoietic repopulating cells and monitoring clonality after transplantation.


hematopoietic stem cell; retroviral vector; nonhuman primate; canine; genotoxicity