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Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism

Gene Therapy volume 23, pages 807–814 (2016)Cite this article

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Abstract

No adeno-associated virus (AAV) capsid has been described in the literature to exhibit a primary oligodendrocyte tropism when a constitutive promoter drives gene expression, which is a significant barrier for efficient in vivo oligodendrocyte gene transfer. The vast majority of AAV vectors, such as AAV1, 2, 5, 6, 8 or 9, exhibit a dominant neuronal tropism in the central nervous system. However, a novel AAV capsid (Olig001) generated using capsid shuffling and directed evolution was recovered after rat intravenous delivery and subsequent capsid clone rescue, which exhibited a >95% tropism for striatal oligodendrocytes after rat intracranial infusion where a constitutive promoter drove gene expression. Olig001 contains a chimeric mixture of AAV1, 2, 6, 8 and 9, but unlike these parental serotypes after intravenous administration Olig001 has very low affinity for peripheral organs, especially the liver. Furthermore, in mixed glial cell cultures, Olig001 exhibits a 9-fold greater binding when compared with AAV8. This novel oligodendrocyte-preferring AAV vector exhibits characteristics that are a marked departure from previously described AAV serotypes.

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Acknowledgements

These studies were supported by Michael J. Fox Foundation and Target ALS grants to TJM, as well as a grant from the Legacy of Angels to SJG. Indirect administrative support for SJG was provided by Research to Prevent Blindness to the UNC Department of Ophthalmology.

Author information

Author notes

  1. N Khan

    Present address: 6Current address: Department of Neuroscience, University of Wisconsin, Madison, WI, USA.,

  2. C L Parker

    Present address: 7Current address: Division of Molecular Pharmaceutics, Eshleman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.,

  3. S J Gray and T J McCown: These authors contributed equally to this work.

Authors and Affiliations

  1. Gene Therapy Center, Chapel Hill, NC, USA

    S K Powell, N Khan, C L Parker, R J Samulski, S J Gray & T J McCown

  2. Department of Pharmacology, Chapel Hill, NC, USA

    R J Samulski

  3. Department of Microbiology and Immunology, Chapel Hill, NC, USA

    G Matsushima

  4. Department of Ophtalmology, Chapel Hill, NC, USA

    S J Gray

  5. Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA

    T J McCown

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  1. S K Powell
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Corresponding authors

Correspondence to S J Gray or T J McCown.

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Competing interests

SJG and TJM are inventors for a filed patent by UNC that includes the Olig001 capsid and is licensed to Asklepios Biopharmaceutical. They have received royalties from Asklepios Biopharmaceutical for this patent. RJS is a scientific co-founder of Asklepios Biopharmaceutical. The remaining authors declare no conflict of interest.

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Powell, S., Khan, N., Parker, C. et al. Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism. Gene Ther 23, 807–814 (2016). https://doi.org/10.1038/gt.2016.62

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