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Bovine AAV transcytosis inhibition by tannic acid results in functional expression of CFTR in vitro and altered biodistribution in vivo

Gene Therapy volume 19, pages 576–581 (2012)Cite this article

Abstract

Bovine adeno-associated virus (BAAV) can enter a cell either through a transcytosis or transduction pathway. We previously demonstrated that particles entering via the transcytosis pathway can be redirected to transduce the cell by blocking particle exocytosis with tannic acid (TA). To investigate whether this approach is useful in lung gene therapy applications, we tested the effect of TA on BAAV transduction in cystic fibrosis airway epithelia in vitro, and in mouse lung in vivo. Our findings suggest that BAAV transcytosis can occur in vivo and that treatment with TA reduces transcytosis and increases lung transduction. TA treatment did not impair the sorting and the activity of the BAAV expressed cystic fibrosis transmembrane regulator membrane protein.

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Acknowledgements

We thank Michael Welsh for his helpful suggestions. This study was supported by an NIH/NIDCR intramural grant to JAC.

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Author notes

  1. G Di Pasquale and L Ostedgaard: These authors contributed equally to this paper.

Authors and Affiliations

  1. Molecular Physiology and Therapeutics Branch,

    G Di Pasquale, W D Swaim & J A Chiorini

  2. , National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA

    G Di Pasquale, W D Swaim & J A Chiorini

  3. Departments of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA

    L Ostedgaard & D Vermeer

  4. Howard Hughes Medical Institute, University of Iowa, Iowa City, IA, USA

    P Karp

Authors
  1. G Di Pasquale
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  2. L Ostedgaard
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  3. D Vermeer
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  4. W D Swaim
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  5. P Karp
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  6. J A Chiorini
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Correspondence to J A Chiorini.

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The authors declare no conflict of interest.

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Di Pasquale, G., Ostedgaard, L., Vermeer, D. et al. Bovine AAV transcytosis inhibition by tannic acid results in functional expression of CFTR in vitro and altered biodistribution in vivo. Gene Ther 19, 576–581 (2012). https://doi.org/10.1038/gt.2011.138

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  • DOI: https://doi.org/10.1038/gt.2011.138

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