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

S. K. Powell, N. Khan, C. L. Parker, R. J. Samulski, G. Matsushima, S. J. Gray, T. J. McCown

Research output: Contribution to journalArticle

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)807-814
Number of pages8
JournalGene Therapy
Volume23
Issue number11
DOIs
StatePublished - Nov 1 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Powell, S. K., Khan, N., Parker, C. L., Samulski, R. J., Matsushima, G., Gray, S. J., & McCown, T. J. (2016). Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism. Gene Therapy, 23(11), 807-814. https://doi.org/10.1038/gt.2016.62