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Adeno-associated virus type 2 vectors: transduction and long-term expression in cerebellar Purkinje cells in vivo is mediated by the fibroblast growth factor receptor 1

bFGFR-1 mediates AAV2 transduction of Purkinje cells

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Abstract

The receptor for adeno-associated virus serotype 2 (AAV2) in Purkinje cells has not been identified, but based on work carried out in non-neuronal cell lines, heparan sulfate proteoglycan is thought to act as a primary receptor, with basic fibroblast growth factor receptor-1 being reported as a co-receptor. In this study, using antibody interference and protein competition strategies, we show specific reduction in Purkinje cell transduction by AAV2 vector in the presence of these inhibitors. We also demonstrate AAV2-mediated transgene expression in Purkinje cells in vivo that extends out to one year post-injection. These results provide new information on fibroblast growth factor receptor-1 involvement in AAV2-mediated transduction of Purkinje cells and have important implications for AAV-mediated treatment of various cerebellar disorders.

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Acknowledgments

This work was supported by Grant # P01 HD032652 from the National Institutes of Health.

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Authors and Affiliations

  1. Gene Therapy Program, Institute of Human Genetics, University of Minnesota, Minneapolis, MN, 55455, USA

    Lalitha R. Belur & R. Scott McIvor

  2. Department of Genetics, Cell Biology and Development, University of Minnesota, 6-160 Jackson Hall, 321 Church St. S. E., Minneapolis, MN, 55455, USA

    Lalitha R. Belur & R. Scott McIvor

  3. Department of Neurosurgery, University of Minnesota, Minneapolis, MN, 55455, USA

    William F. Kaemmerer & Walter C. Low

  4. Medtronic Inc, Bioscience LT220, 710 Medtronic Parkway, Minneapolis, MN, 55432, USA

    William F. Kaemmerer

Authors
  1. Lalitha R. Belur
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  2. William F. Kaemmerer
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  3. R. Scott McIvor
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  4. Walter C. Low
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Correspondence to R. Scott McIvor.

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Belur, L.R., Kaemmerer, W.F., McIvor, R.S. et al. Adeno-associated virus type 2 vectors: transduction and long-term expression in cerebellar Purkinje cells in vivo is mediated by the fibroblast growth factor receptor 1. Arch Virol 153, 2107–2110 (2008). https://doi.org/10.1007/s00705-008-0222-7

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  • DOI: https://doi.org/10.1007/s00705-008-0222-7

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