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Modulation of Treg function improves adenovirus vector-mediated gene expression in the airway

Gene Therapy volume 21, pages 219–224 (2014)Cite this article

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Abstract

Virus vector-mediated gene transfer has been developed as a treatment for cystic fibrosis (CF) airway disease, a lethal inherited disorder caused by somatic mutations in the cystic fibrosis transmembrane conductance regulator gene. The pathological proinflammatory environment of CF as well as the naïve and adaptive immunity induced by the virus vector itself limits the effectiveness of gene therapy for CF airway. Here, we report the use of an HDAC inhibitor, valproic acid (VPA), to enhance the activity of the regulatory T cells (Treg) and to improve the expression of virus vector-mediated gene transfer to the respiratory epithelium. Our study demonstrates the potential utility of VPA, a drug used for over 50 years in humans as an anticonvulsant and mood-stabilizer, in controlling inflammation and improving the efficacy of gene transfer in CF airway.

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Acknowledgements

We thank the members of the Vector Core, Animal Models Core and Cell Morphology Core of the Gene Therapy Program at the University of Pennsylvania for assistance with these studies. Flow cytometry was performed at the Abramson Cancer Center Flow Cytometry and Cell Sorting Shared Resource, a member of Path BioResource, in the Perelman School of Medicine of the University of Pennsylvania, which was established in part by equipment grants from the NIH Shared Instrument Program, and receives support from NIH P30 CA016520 from the National Cancer Institute. This work was supported by grants from the National Institutes of Health grants P30DK047757 (Pilot grant) and P01AI073489.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA

    Y Nagai, M P Limberis & H Zhang

  2. Gene Therapy Program, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA

    M P Limberis

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  1. Y Nagai
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Correspondence to H Zhang.

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Nagai, Y., Limberis, M. & Zhang, H. Modulation of Treg function improves adenovirus vector-mediated gene expression in the airway. Gene Ther 21, 219–224 (2014). https://doi.org/10.1038/gt.2013.78

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