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Epidermal growth factor receptor is a co-receptor for adeno-associated virus serotype 6

Nature Medicine volume 16, pages 662–664 (2010)Cite this article

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Abstract

A key step in gene therapy is the efficient transfer of genes in a cell type– and tissue-specific manner. To better understand the mechanism of adeno-associated virus serotype 6 (AAV6) transduction, we used comparative gene analysis (CGA) combined with pathway visualization software to identify a positive correlation between AAV6 transduction and epidermal growth factor receptor (EGFR) expression. Subsequent experiments suggested that EGFR is necessary for vector internalization and probably functions as a co-receptor for AAV6.

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Figure 1: AAV6 transduction corresponds with EGFR expression and function.
Figure 2: AAV6 mediated transduction of EGFR expressing tumors and delivery of cytotoxic transgene, HSVtk, followed by ganciclovir treatment results in a significant reduction in tumor growth.

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Acknowledgements

We would like to thank B. Handelman for expertise in AAV production, M. Kunkel and S. Holbeck for assistance with the National Cancer Institute Developmental Therapeutics Program and the COMPARE program and T. Jovanka for philosophical guidance.

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Authors and Affiliations

  1. Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, US National Institutes of Health (NIH), Bethesda, Maryland, USA

    Melodie L Weller, Michael Schmidt & John A Chiorini

  2. Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, USA

    Panomwat Amornphimoltham & J Silvio Gutkind

  3. Division of Enterprise and Custom Applications Center for Information Technology, Custom Applications Branch, NIH, Bethesda, Maryland, USA

    Paul A Wilson

Authors
  1. Melodie L Weller
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  2. Panomwat Amornphimoltham
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  3. Michael Schmidt
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  4. Paul A Wilson
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  5. J Silvio Gutkind
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  6. John A Chiorini
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Contributions

M.L.W. performed experiments, analyzed data and wrote the paper; P.A. performed experiments, analyzed data and wrote the paper; M.S. performed experiments and analyzed data; P.A.W. developed software used in CGA; J.S.G. contributed tumor model and head-and-neck tumor cell lines and analyzed data; J.A.C. analyzed data and wrote the paper. All authors were involved in the review and editing of the paper.

Corresponding author

Correspondence to John A Chiorini.

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The authors declare no competing financial interests.

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Supplementary Figs. 1–3 and Supplementary Methods (PDF 1131 kb)

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Weller, M., Amornphimoltham, P., Schmidt, M. et al. Epidermal growth factor receptor is a co-receptor for adeno-associated virus serotype 6. Nat Med 16, 662–664 (2010). https://doi.org/10.1038/nm.2145

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  • DOI: https://doi.org/10.1038/nm.2145

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