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Efficient transduction of non-human primate motor neurons after intramuscular delivery of recombinant AAV serotype 6

Gene Therapy volume 17, pages 141–146 (2010)Cite this article

Abstract

Retrograde transport of viral vectors in the rodent spinal cord provides a powerful means to administer a therapeutic transgene from the innervated musculature. With the aim of scaling up this approach to non-human primates, we have injected recombinant adeno-associated vectors (rAAV) serotype 6 expressing enhanced green fluorescent protein (eGFP) into the gastrocnemius muscle of African green monkeys to determine whether this results in efficient transgene delivery to lumbar motor neurons. Cells expressing eGFP were observed across more than 1 cm of the spinal cord 4 weeks after intramuscular injection, reaching more than half of motor neurons in some cross-sections. Furthermore, quantitative PCR on the spinal cord tissue confirmed that eGFP expression within motor neurons was due to bona fide retrograde transport of the vector genome from the muscle. Although infiltrations of macrophages and lymphocytes were observed in the rAAV2/6-injected muscle, there was no detectable immune response within the transduced region of the spinal cord. These findings imply that retrograde delivery of rAAV serotype 6 in a primate species constitutes a non-invasive and robust approach to transduce motor neurons, a crucial target cell population in neurodegenerative disorders, such as amyotrophic lateral sclerosis and spinal muscular atrophy.

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Acknowledgements

We thank K Löw, V Setola, F Santoni de Sio, JC Bensadoun, F Pidoux, C Sadeghi, V Padrun and the staff at St. Kitts Biomedical for their technical assistance, especially E Nisbett. This work was supported by the Bruno and Ilse Frick Foundation and by the Axion Research Foundation.

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Authors and Affiliations

  1. Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland

    C Towne, B L Schneider, D Kieran & P Aebischer

  2. Departments of Psychiatry & Neurosurgery, Yale University School of Medicine, New Haven, CT, USA

    D E Redmond Jr

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  1. C Towne
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  2. B L Schneider
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  3. D Kieran
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  4. D E Redmond Jr
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  5. P Aebischer
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Correspondence to P Aebischer.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Towne, C., Schneider, B., Kieran, D. et al. Efficient transduction of non-human primate motor neurons after intramuscular delivery of recombinant AAV serotype 6. Gene Ther 17, 141–146 (2010). https://doi.org/10.1038/gt.2009.119

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