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  • Original Article
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Evidence for the in vivo safety of insulated foamy viral vectors

Gene Therapy volume 24, pages 187–198 (2017)Cite this article

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Abstract

Retroviral vector-mediated stem cell gene therapy is a promising approach for the treatment of hematopoietic disorders. However, genotoxic side effects from integrated vector proviruses are a significant concern for the use of retroviral vectors in the clinic. Insulated foamy viral (FV) vectors are potentially safer retroviral vectors for hematopoietic stem cell gene therapy. We evaluated two newly identified human insulators, A1 and A2, for use in FV vectors. These insulators had moderate insulating capacity and higher titers than previously developed insulated FV vectors. The A1-insulated FV vector was chosen for comparison with the previously described 650cHS4-insulated FV vector in human cord blood CD34+ repopulating cells in an immunodeficient mouse model. To maximize the effects of the insulators on the safety of FV vectors, FV vectors containing a highly genotoxic spleen focus forming virus promoter were used to elicit differences in genotoxicity. In vivo, the A1-insulated FV vector showed an approximate 50% reduction in clonal dominance compared with either the 650cHS4-insulated or control FV vectors, although the transduction efficiency of the A1-insulated vector was higher. This data suggests that the A1-insulated FV vector is promising for future preclinical and clinical studies.

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Acknowledgements

This work was supported by NIH grants AI097100 and AI102672 (GDT). We acknowledge the WSU Spokane flow cytometry core.

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  1. H Wang

    Present address: 4Current address: Altius Institute for Biomedical Sciences Seattle, WA 98121, USA.,

Authors and Affiliations

  1. School of Molecular Biosciences, Washington State University, Pullman, WA, USA

    D L Browning & G D Trobridge

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

    E M Everson, D J Leap, J D Hocum & G D Trobridge

  3. Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA, USA

    H Wang & G Stamatoyannopoulos

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  1. D L Browning
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Correspondence to G D Trobridge.

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Browning, D., Everson, E., Leap, D. et al. Evidence for the in vivo safety of insulated foamy viral vectors. Gene Ther 24, 187–198 (2017). https://doi.org/10.1038/gt.2016.88

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