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Abstract
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 microliter; 5 x 10(4) particles) produced neuronal
beta-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 microliter) in the adult rat, beta-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 beta-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.