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Viruses 2012, 4(12), 3572-3588;

Large Animal Models for Foamy Virus Vector Gene Therapy

Department of Pharmaceutical Sciences, Washington State University, 99164-6534, Pullman, WA, USA
School of Molecular Biosciences, Pullman, WA, USA
Institute for Transfusion Medicine, University Hospital Essen, Virchowstr. 179, 45122 Essen, Germany
Fred Hutchinson Cancer Research Center Clinical Research Division, 98109-1024, Seattle, WA, USA
University of Washington School of Medicine, Seattle, WA, USA
Authors to whom correspondence should be addressed.
Received: 15 October 2012 / Revised: 19 November 2012 / Accepted: 28 November 2012 / Published: 7 December 2012
(This article belongs to the Special Issue Recent Progress in Foamy Virus (FV) Research)
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Foamy virus (FV) vectors have shown great promise for hematopoietic stem cell (HSC) gene therapy. Their ability to efficiently deliver transgenes to multi-lineage long-term repopulating cells in large animal models suggests they will be effective for several human hematopoietic diseases. Here, we review FV vector studies in large animal models, including the use of FV vectors with the mutant O6-methylguanine-DNA methyltransferase, MGMTP140K to increase the number of genetically modified cells after transplantation. In these studies, FV vectors have mediated efficient gene transfer to polyclonal repopulating cells using short ex vivo transduction protocols designed to minimize the negative effects of ex vivo culture on stem cell engraftment. In this regard, FV vectors appear superior to gammaretroviral vectors, which require longer ex vivo culture to effect efficient transduction. FV vectors have also compared favorably with lentiviral vectors when directly compared in the dog model. FV vectors have corrected leukocyte adhesion deficiency and pyruvate kinase deficiency in the dog large animal model. FV vectors also appear safer than gammaretroviral vectors based on a reduced frequency of integrants near promoters and also near proto-oncogenes in canine repopulating cells. Together, these studies suggest that FV vectors should be highly effective for several human hematopoietic diseases, including those that will require relatively high percentages of gene-modified cells to achieve clinical benefit. View Full-Text
Keywords: foamy virus vectors; gene therapy; hematopoietic stem cells; animal models foamy virus vectors; gene therapy; hematopoietic stem cells; animal models

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Trobridge, G.D.; Horn, P.A.; Beard, B.C.; Kiem, H.-P. Large Animal Models for Foamy Virus Vector Gene Therapy. Viruses 2012, 4, 3572-3588.

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