Expression mediated by three partial sequences of the human tyrosine hydroxylase promoter in vivo.
The use of viral vectors to transfect postmitotic neurons has provided an important research tool, and it offers promise for treatment of neurologic disease. The utility of vectors is enhanced by the use of selective promoters that permit control of the cellular site of expression. One potential clinical application is in the neurorestorative treatment of Parkinson's disease by the induction of new axon growth. However, many of the genes with an ability to restore axons have oncogenic potential. Therefore, clinical safety would be enhanced by restriction of expression to neurons affected by the disease, particularly dopamine neurons. To achieve this goal we have evaluated in vivo three partial sequences of the promoter for human tyrosine hydroxylase, the rate limiting enzyme in catecholamine synthesis. All sequences induced expression in dopamine neurons. None of them induced expression in glia or in nondopaminergic neurons in striatum or cortex. We conclude that these sequences have potential use for targeting dopamine neurons in research and clinical applications.
Department of Neurology, Columbia University , New York, NY, USA.
Anne-Sophie
AS
Rolland
Department of Neurology, Columbia University , New York, NY, USA.
Tatyana
T
Kareva
Department of Neurology, Columbia University , New York, NY, USA.
Olga
O
Yarygina
Department of Neurology, Columbia University , New York, NY, USA.
Nikolai
N
Kholodilov
Department of Neurology, Columbia University, New York, NY, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
Robert E
RE
Burke
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