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

Publication Type	Academic Article
Authors	Kaplitt M, Leone P, Samulski R, Xiao X, Pfaff D, O'Malley K, During M
Journal	Nat Genet
Volume	8
Issue	2
Pagination	148-54
Date Published	10/01/1994
ISSN	1061-4036
Keywords	Brain, Dependovirus, Gene Expression Regulation, Viral, Genetic Therapy, Genetic Vectors, Parkinson Disease, Secondary, Recombinant Fusion Proteins, Tyrosine 3-Monooxygenase
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.
DOI	10.1038/ng1094-148
PubMed ID	7842013