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Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain

Nature Genetics volume 8, pages 148–154 (1994)Cite this article

Abstract

Adeno-associated viral (AAV) vectors are non-pathogenic, integrating DNA vectors in which all viral genes are removed and helper virus is completely eliminated. To evaluate this system in the post-mitotic cells of the brain, we found that an AAV vector containing the LacZ gene (AAVIac) resulted in expression of β-galactosidase up to three months post-injection in vivo. A second vector expressing human tyrosine hydroxylase (AAVth) was injected into the denervated striatum of unilateral 6-hydroxydopamine-lesioned rats. Tyrosine hydroxylase (TH) immunoreactivity was detectable in striatal neurons and glia for up to four months and we also found significant behavioural recovery in lesioned rats treated with AAVth versus AAVIac controls. Safe and stable TH gene transfer into the denervated striatum may have potential for the genetic therapy of Parkinson's disease.

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Author information

Authors and Affiliations

  1. Molecular Pharmacology and Neurogenetics Laboratory, Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, 06520-8039, USA

    Michael G. Kaplitt, Paola Leone & Matthew J. During

  2. Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, New York, 10021, USA

    Michael G. Kaplitt & Donald W. Pfaff

  3. Gene Therapy Center, University of North Carolina, Chapel Hill, North Carolina, 27599, USA

    Richard J. Samulski

  4. Merlin Pharmaceuticals, New York, New York, 10014, USA

    Xiao Xiao

  5. Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri, 63110, USA

    Karen L. O'Malley

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  1. Michael G. Kaplitt
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Kaplitt, M., Leone, P., Samulski, R. et al. Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nat Genet 8, 148–154 (1994). https://doi.org/10.1038/ng1094-148

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