PMID: 10397644: Recombinant adeno-associated virus (AAV) drives constitutive production of glutamate decarboxylase in neural cell lines.

[Hans van der Genugten <genugten@xxxxxxxxxxxxx>]

J Neurosci Res 1999 Jul 1;57(1):137-48

Recombinant adeno-associated virus (AAV) drives constitutive production of
glutamate decarboxylase in neural cell lines.

Mi J, Chatterjee S, Wong KK, Forbes C, Lawless G, Tobin AJ
Department of Physiological Sciences, University of California, Los Angeles,
USA.

Many neurological disorders result directly or indirectly from the loss of
inhibitory function. Engineering the production of GABA, an inhibitory
neurotransmitter, may therefore be able at least partly to restore the lost
inhibition seen in epilepsy, Parkinson's disease, or Huntington's disease.
In this article, we describe a set of recombinant adeno-associated viruses
(AAVs) that can deliver cDNAs encoding the GABA-producing enzyme, glutamate
decarboxylase (GAD), directly into neural cells. We have characterized these
recombinant AAVs in several cell lines derived from the CNS. These
recombinant AAVs effectively transduced all neural cell lines, although with
different efficiencies. Transduction occurred in both proliferating and
nonproliferating cells, but actively proliferating cell lines had
approximately six times greater transduction efficiency than
nonproliferating cells. Furthermore, these AAVs maintained long-term
expression of GAD in an astrocytic cell line for at least seven passages.
These recombinant AAVs are promising vehicles for investigating the
potential therapeutic effects of GABA in animal models of epilepsy and
neurodegenerative diseases.

PMID: 10397644, UI: 99323773
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