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Quantification of HSV-1-mediated expression of the ferritin MRI reporter in the mouse brain

Gene Therapy volume 20, pages 589–596 (2013)Cite this article

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Abstract

The development of effective strategies for gene therapy has been hampered by difficulties verifying transgene delivery in vivo and quantifying gene expression non-invasively. Magnetic resonance imaging (MRI) offers high spatial resolution and three-dimensional views, without tissue depth limitations. The iron-storage protein ferritin is a prototype MRI gene reporter. Ferritin forms a paramagnetic ferrihydrite core that can be detected by MRI via its effect on the local magnetic field experienced by water protons. In an effort to better characterize the ferritin reporter for central nervous system applications, we expressed ferritin in the mouse brain in vivo using a neurotropic herpes simplex virus type 1 (HSV-1). We computed three-dimensional maps of MRI transverse relaxation rates in the mouse brain with ascending doses of ferritin-expressing HSV-1. We established that the transverse relaxation rates correlate significantly to the number of inoculated infectious particles. Our results are potentially useful for quantitatively assessing limitations of ferritin reporters for gene therapy applications.

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Acknowledgements

This work was funded by the NIH Grants R01-EB005740 and P41-EB001977 and NSF Graduate Research Fellowship (BI) 2007053507.

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Authors and Affiliations

  1. Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA

    B Iordanova & E T Ahrens

  2. Pittsburgh NMR Center for Biomedical Research, Pittsburgh, PA, USA

    B Iordanova, T K Hitchens & E T Ahrens

  3. Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    W F Goins & D S Clawson

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  1. B Iordanova
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  2. W F Goins
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Correspondence to E T Ahrens.

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ETA is a consultant for Celsense, Inc., Pittsburgh, PA, USA.

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Iordanova, B., Goins, W., Clawson, D. et al. Quantification of HSV-1-mediated expression of the ferritin MRI reporter in the mouse brain. Gene Ther 20, 589–596 (2013). https://doi.org/10.1038/gt.2012.70

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  • DOI: https://doi.org/10.1038/gt.2012.70

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