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Trans-neuronal transduction of spinal neurons following cortical injection and anterograde axonal transport of a bicistronic AAV1 vector

Gene Therapy volume 23, pages 231–236 (2016)Cite this article

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Abstract

Adeno-associated viral (AAV) vectors are one of the most promising gene delivery systems to the central nervous system. We now report, that AAV1 can be used to express transgenes trans-neuronally in neurons distant from the injection site. Specifically, intracortical injection of a bicistronic AAV1 vector trans-neuronally transduced spinal neurons as shown by fluorescence microscopy, the presence of AAV genome and AAV transcript in the contralateral spinal cord. Prior pyramidotomy abolished spinal transduction, confirming anterograde axonal transport of AAV1 in the corticospinal tract. These observations demonstrate the potential of bicistronic AAV1 for trans-neuronal expression of therapeutic transgenes in neurological disorders or reporter genes in connectivity studies.

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Acknowledgements

This work was funded by the European Research Council under the EU's Seventh Framework Programme (FP/2007–2013) Grant Agreement no. 309731, by the Henry Smith Charity and by a Nathalie Rose Barr PhD studentship from The International Spinal Research Trust which included funding from the Rosetrees Trust. Thanks to Hansruedi Bueler (University of Kentucky, KY, USA) for the psubCMV-2A-WPRE plasmid. We thank the Penn Vector Core at the Gene Therapy Program of the University of Pennsylvania for production of AAVs.

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  1. T H Hutson and C Kathe: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Brain Sciences, Department of Medicine, Centre for Restorative Neuroscience, Imperial College London, London, UK

    T H Hutson

  2. Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King’s College London, London, UK

    C Kathe & L D F Moon

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  1. T H Hutson
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Correspondence to T H Hutson or L D F Moon.

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Hutson, T., Kathe, C. & Moon, L. Trans-neuronal transduction of spinal neurons following cortical injection and anterograde axonal transport of a bicistronic AAV1 vector. Gene Ther 23, 231–236 (2016). https://doi.org/10.1038/gt.2015.103

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