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

Michael G. Kaplitt, Paola Leone, Richard J. Samulski, Xiao Xiao, Donald W. Pfaff, Karen L. O'Malley, Matthew J. During

Research output: Contribution to journalArticlepeer-review

882 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)148-154
Number of pages7
JournalNature Genetics
Volume8
Issue number2
DOIs
StatePublished - Oct 1994

All Science Journal Classification (ASJC) codes

  • Genetics

Fingerprint Dive into the research topics of 'Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain'. Together they form a unique fingerprint.

Cite this