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Foamy viral vector integration sites in SCID-repopulating cells after MGMTP140K-mediated in vivo selection

Gene Therapy volumeĀ 22,Ā pages 591ā€“595 (2015)Cite this article

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Abstract

Foamy virus (FV) vectors are promising for hematopoietic stem cell (HSC) gene therapy but preclinical data on the clonal composition of FV vector-transduced human repopulating cells is needed. Human CD34+ human cord blood cells were transduced with an FV vector encoding a methylguanine methyltransferase (MGMT)P140K transgene, transplanted into immunodeficient NOD/SCID IL2RĪ³null mice, and selected in vivo for gene-modified cells. The retroviral insertion site profile of repopulating clones was examined using modified genomic sequencing PCR. We observed polyclonal repopulation with no evidence of clonal dominance even with the use of a strong internal spleen focus forming virus promoter known to be genotoxic. Our data supports the use of FV vectors with MGMTP140K for HSC gene therapy but also suggests additional safety features should be developed and evaluated.

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Acknowledgements

This research was supported in part by NIH grants AI097100 (HPK, DJR and GDT), and AI102672 (GDT). We thank Diana Browning for advice and assistance with flow cytometry.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Washington State University, Spokane, WA, USA

    M E Olszko,Ā I Linde,Ā D T Rae,Ā P Trobridge,Ā J D HocumĀ &Ā G D Trobridge

  2. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    J E AdairĀ &Ā H-P Kiem

  3. Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA

    D J Rawlings

  4. School of Molecular Biosciences, Washington State University, Pullman, Washington, USA

    G D Trobridge

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  1. M E Olszko
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Correspondence to G D Trobridge.

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Olszko, M., Adair, J., Linde, I. et al. Foamy viral vector integration sites in SCID-repopulating cells after MGMTP140K-mediated in vivo selection. Gene Ther 22, 591ā€“595 (2015). https://doi.org/10.1038/gt.2015.20

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