Transient demyelination increases the efficiency of retrograde AAV transduction

Edmund R. Hollis, Pouya Jamshidi, Ariana O. Lorenzana, Jae K. Lee, Steven J. Gray, Richard J. Samulski, Binhai Zheng, Mark H. Tuszynski

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14 Scopus citations

Abstract

Adeno-associated virus (AAV) is capable of mediating retrograde viral transduction of central and peripheral neurons. This occurs at a relatively low efficiency, which we previously found to be dependent upon capsid serotype. We sought to augment retrograde transduction by providing increased axonal access to peripherally delivered AAV. Others have described utilizing full transection of peripheral nerves to mediate retrograde viral transduction of motor neurons. Here, we examined the ability of a transient demyelinating event to modulate levels of retrograde AAV transduction. Transient demyelination does not cause lasting functional deficits. Ethidium bromide (EtBr)-induced transient demyelination of the sciatic nerve resulted in significant elevation of retrograde transduction of both motor and sensory neurons. Retrograde transduction levels of motor neurons and heavily myelinated, large-diameter sensory neurons increased at least sixfold following peripheral delivery of self-complementary AAV serotype 1 (scAAV1) and serotype 2 (scAAV2), when preceded by demyelination. These findings identify a means of significantly enhancing retrograde vector transport for use in experimental paradigms requiring either retrograde neuronal identification and gene expression, or translational treatment paradigms.

Original languageEnglish (US)
Pages (from-to)1496-1500
Number of pages5
JournalMolecular Therapy
Volume18
Issue number8
DOIs
StatePublished - Aug 2010

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Hollis, E. R., Jamshidi, P., Lorenzana, A. O., Lee, J. K., Gray, S. J., Samulski, R. J., Zheng, B., & Tuszynski, M. H. (2010). Transient demyelination increases the efficiency of retrograde AAV transduction. Molecular Therapy, 18(8), 1496-1500. https://doi.org/10.1038/mt.2010.97