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Gene delivery to rat and human Schwann cells and nerve segments: a comparison of AAV 1–9 and lentiviral vectors

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Abstract

Schwann cells (SCs) in an injured peripheral nerve form pathways for regenerating axons. Although these cells initially support regeneration, SCs lose their pro-regenerative properties following a prolonged period of denervation. Gene transfer to SC can enhance their therapeutic potential. In this article, we compared adeno-associated viral (AAV) vectors based on serotypes 1–9 for their capability to transduce cultured primary rat and human SCs and nerve segments. AAV1 is the best serotype to transduce rat SCs, whereas AAV2 and AAV6 performed equally well in human SCs. Transduction of monolayers of cultured rat and human SCs did not accurately predict the transduction efficiency in nerve segments. Rat nerve segments could be genetically modified equally well by a set of four AAV vectors (AAV1, AAV5, AAV7, AAV9), whereas AAV2 was superior in human nerve segments. The current experiments were undertaken as a first step towards future clinical implementation of ex vivo AAV-based gene therapy in surgical nerve repair. The transduction of rat and human SCs and nerve segments by entirely different AAV serotypes, as documented here, highlights one of the challenges of translating gene therapy from experimental animals to human patients.

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Authors and Affiliations

  1. Department of Neuroregeneration, Netherlands Insititute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands

    S A Hoyng, F De Winter, S Gnavi, L van Egmond, C L Attwell, M R Tannemaat, J Verhaagen & M J A Malessy

  2. Department of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands

    S A Hoyng, F De Winter & M J A Malessy

  3. Neuroscience Institute of the Cavalieri Ottolenghi Foundation and Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

    S Gnavi

  4. Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands

    M R Tannemaat

  5. Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

    J Verhaagen

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  1. S A Hoyng
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  2. F De Winter
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  3. S Gnavi
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  4. L van Egmond
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Hoyng, S., De Winter, F., Gnavi, S. et al. Gene delivery to rat and human Schwann cells and nerve segments: a comparison of AAV 1–9 and lentiviral vectors. Gene Ther 22, 767–780 (2015). https://doi.org/10.1038/gt.2015.47

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