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Intracerebroventricular delivery of self-complementary adeno-associated virus serotype 9 to the adult rat brain

Gene Therapy volume 23, pages 401–407 (2016)Cite this article

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Abstract

Gene therapy for the central nervous system is poised to become a powerful treatment for numerous neurological disorders. Adeno-associated viral vectors based on serotype 9 (AAV9) have proven themselves to be strong candidates for delivering gene-based therapies throughout the brain and spinal cord when administered intravenously, intrathecally, intracisternally, and intracerebroventricularly (i.c.v.). Previous studies of i.c.v.-delivered self-complimentary AAV9 have been performed in neonatal mice with delivery of a single dose. However, before clinical trials can be considered, more information is required about the dose–response relationship for transduction efficiency in adult animals. In the current study, three doses of self-complementary AAV9 were administered to adult rats. High levels of transduction were observed in the hippocampus, cerebellum and cerebral cortex, and transduction increased with increasing dosage. Both neurons and astrocytes were transduced. There was no evidence of astrocytosis at the doses tested. Preliminary results from pigs receiving i.c.v. self-complementary AAV9 are also presented. The results of this study will serve to inform dosing studies in large animal models before clinical testing.

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Acknowledgements

This work was funded through donations from the Virginia Gentlemen Foundation. The scAAV9-GFP for the rat studies was kindly provided by Marco Passini (Genzyme). Sectioning and staining of the pig brain was provided by RegenX.

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Authors and Affiliations

  1. Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA

    A Donsante, Z McEachin, J Riley, D M O'Connor & N M Boulis

  2. Department of Biology, Widener University, Chester, PA, USA

    C H Leung & L Kanz

Authors
  1. A Donsante
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  2. Z McEachin
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  3. J Riley
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  4. C H Leung
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  5. L Kanz
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  6. D M O'Connor
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  7. N M Boulis
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Correspondence to N M Boulis.

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The authors declare no conflict of interest.

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Donsante, A., McEachin, Z., Riley, J. et al. Intracerebroventricular delivery of self-complementary adeno-associated virus serotype 9 to the adult rat brain. Gene Ther 23, 401–407 (2016). https://doi.org/10.1038/gt.2016.6

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