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Transduction of human neural progenitor cells with foamy virus vectors for differentiation-dependent gene expression

Gene Therapy volume 16, pages 349–358 (2009)Cite this article

Abstract

Neural progenitor cells are potential vehicles for delivery of therapeutic agents into the brain. Differentiation-dependent promoters may be useful to target the therapeutic transgene expression to specific neural cell types. Here we explored the potential of vectors based on the foamy virus (FV) for genetic engineering of neural progenitor cells. We demonstrate that FV vectors can mediate stable long-term constitutive expression of the enhanced green fluorescent protein (EGFP) in neural progenitor cells. For differentiation-dependent gene expression, we constructed a FV vector with an internal expression cassette containing the human 2.2 kb promoter (Gfa2) of the astrocyte-specific glial fibrillary acidic protein (GFAP) and sequences encoding EGFP. We show FV-vector-mediated delivery of the Gfa2-egfp transgene into the human neural stem cell line HNSC.100 and differentiation-dependent expression in stably transduced cell populations. Differentiation of the FV-transduced HNSC.100 cells to astrocytes upregulated expression of both the Gfa2-egfp transgene and the native gfap gene, confirming differentiation-dependent activation of the transduced Gfa2 promoter. These results demonstrate that differentiation-dependent gene expression can be achieved by FV-vector-mediated gene transfer to neural progenitor cells. Our findings support the use of FV vectors for the genetic engineering of neural progenitor cells for therapeutic and research applications.

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Acknowledgements

We thank Elisabeth Kremmer (Munich) and Katrin Peters (Würzburg) for reagents and advice and Kamyar Hadian for critical reading of the paper. This study was supported by the German Research Council (DFG), Priority Program (SPP) 1230 and by the Research Program ‘Infection and Immunity’ of the Helmholtz Association.

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Author notes

  1. I Rothenaigner and S Kramer: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Virology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany

    I Rothenaigner, S Kramer, M Meggendorfer & R Brack-Werner

  2. Institute of Virology und Immunbiology, University of Wuerzburg, Wuerzburg, Germany

    A Rethwilm

  3. Clinical Cooperation Group ‘Immune-Monitoring’, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany

    R Brack-Werner

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  1. I Rothenaigner
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Correspondence to R Brack-Werner.

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Rothenaigner, I., Kramer, S., Meggendorfer, M. et al. Transduction of human neural progenitor cells with foamy virus vectors for differentiation-dependent gene expression. Gene Ther 16, 349–358 (2009). https://doi.org/10.1038/gt.2008.173

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