Differential and persistent expression patterns of CNS gene transfer by an adeno-associated virus (AAV) vector Public Deposited

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  • Breese, George R.
    • ORCID: https://orcid.org/0000-0001-8579-9007
    • Affiliation: School of Medicine, Department of Pharmacology, Neuroscience Center, Department of Psychiatry
  • Xiao, Xiao
    • Affiliation: School of Medicine, Gene Therapy Center
  • Crown, Thomas J.
    • Affiliation: School of Medicine, Neuroscience Center, Department of Psychiatry, Gene Therapy Center
  • Samulski, R. Jude
    • Affiliation: School of Medicine, Department of Pharmacology, Gene Therapy Center
  • Li, Juan
    • Affiliation: School of Medicine, Gene Therapy Center
  • Safe, long-term gene expression is a primary criteria for effective gene therapy in the brain, so studies were initiated to evaluate adeno-associated virus (AAV) vector transfer of a reporter gene into specific sites of the rat brain. In the 4 day old rat, site infusions of AAV-CMV-lacZ (1 μ1; 5 × 104 particles) produced neuronal β-galactosidase gene expression 3 weeks later in the hippocampus and inferior colliculus, but not in the cerebral cortex. Seven days after infusion of AAV-CMV-lacZ viral vectors (1 μ1) in the adult rat, β-galactosidase gene expression was found in the olfactory tubercle, caudate, hippocampus, piriform cortex and inferior colliculus, primarily in multipolar neurons close to the infusion site. Three months after vector microinfusion, similar levels of gene expression remained in the olfactory tubercle and the inferior colliculus, with some reduction found in the caudate, but substantial reductions in β-galactosidase gene expression occurred in the hippocampus and piriform cortex. In no case were obvious signs of toxicity noted. Therefore, AAV vectors can transfer foreign genes into the adult and neonatal CNS, but the pattern and longevity of gene expression depends upon the area of brain being studied.
Date of publication
  • doi:10.1016/0006-8993(95)01488-8
  • 2-s2.0-0030003480
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Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • Brain Research
Journal volume
  • 713
Journal issue
  • 1-2
Page start
  • 99
Page end
  • 107
  • English
  • Postprint
  • 0006-8993

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