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Transduction efficiency of neurons and glial cells by AAV-1, -5, -9, -rh10 and -hu11 serotypes in rat spinal cord following contusion injury

Gene Therapy volume 21, pages 991–1000 (2014)Cite this article

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Abstract

Adeno-associated viruses (AAVs) are a promising system for therapeutic gene delivery to neurons in a number of neurodegenerative conditions including spinal cord injuries (SCIs). Considering the role of macrophages and glia in the progression of ‘secondary damage’, we searched for the optimal vectors for gene transfer to both neurons and glia following contusion SCI in adult rats. Contusion models share many similarities to most human spinal cord traumas. Several AAV serotypes known for their neuronal tropism expressing enhanced green-fluorescent protein (GFP) were injected intraspinally following thoracic T10 contusion. We systematically compared the transduction efficacy and cellular tropism of these vectors for neurons, macrophages/microglia, oligodendrocytes, astrocytes and NG2-positive glial cells following contusion SCI. No additional changes in inflammatory responses or behavioral performance were observed for any of the vectors. We identified that AAV-rh10 induced robust transduction of both neuronal and glial cells. Even though efficacy to transduce neurons was comparable to already established AAV-1, AAV-5 and AAV-9, AAV-rh10 transduced significantly higher number of macrophages/microglia and oligodendrocytes in damaged spinal cord compared with other serotypes tested. Thus, AAV-rh10 carries promising potential as a gene therapy vector, particularly if both the neuronal and glial cell populations in damaged spinal cord are targeted.

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Acknowledgements

We would like to thank Sharee Sandler for technical support, Lisa Schnell for discussions and the Penn Vector Core at the University of Pennsylvania for the development and production of AAV vectors and in particular Julie Johnston for her generosity and support. The research was supported by Merit Review Funding from the Department of Veterans Affairs (VLA), the New York State Spinal Cord Injury Research Board (JML, VLA) and the Department of Defense (VLA).

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Authors and Affiliations

  1. Northport Veterans Affairs Medical Center, Northport, NY, USA

    H A Petrosyan, V Alessi, V Singh, A S Hunanyan & V L Arvanian

  2. Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY, USA,

    H A Petrosyan, V Alessi, A S Hunanyan, J M Levine & V L Arvanian

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  1. H A Petrosyan
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Correspondence to V L Arvanian.

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Petrosyan, H., Alessi, V., Singh, V. et al. Transduction efficiency of neurons and glial cells by AAV-1, -5, -9, -rh10 and -hu11 serotypes in rat spinal cord following contusion injury. Gene Ther 21, 991–1000 (2014). https://doi.org/10.1038/gt.2014.74

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