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 (AAVlac) resulted in expression of beta-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 AAVlac controls. Safe and stable TH gene transfer into the denervated striatum may have potential for the genetic therapy of Parkinson's disease.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenoviruses, Human / physiology
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Animals
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Apomorphine / toxicity
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Behavior, Animal / drug effects
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Brain / metabolism*
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Brain / pathology
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Corpus Striatum
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Cytomegalovirus / genetics
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Dependovirus / genetics*
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Gene Expression Regulation, Viral*
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Genes, Reporter
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Genes, Synthetic
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Genetic Therapy*
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Genetic Vectors*
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Helper Viruses / physiology
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Humans
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Male
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Microinjections
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Oxidopamine / toxicity
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Parkinson Disease, Secondary / chemically induced
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Parkinson Disease, Secondary / therapy*
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Promoter Regions, Genetic
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Rats
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Rats, Sprague-Dawley
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Recombinant Fusion Proteins / biosynthesis*
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Simian virus 40 / genetics
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Substantia Nigra / metabolism
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Substantia Nigra / pathology
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Transfection
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Tyrosine 3-Monooxygenase / biosynthesis
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Tyrosine 3-Monooxygenase / genetics*
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beta-Galactosidase / genetics
Substances
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Recombinant Fusion Proteins
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Oxidopamine
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Tyrosine 3-Monooxygenase
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beta-Galactosidase
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Apomorphine