Description The longterm goal of this grant application is to develop a defective HSV-1 vector system that can be used for human gene therapy. HSV-1 vectors are particularly attractive for gene therapy of neurodegenerative diseases in the aging brain, such as Parkinson disease, but HSV-1 vectors may also be applicable to other neurological disorders. The investigators have shown that HSV-1 vectors that express TH can direct long-term biochemical and behavioral recovery in a rodent model of PD. Additionally, they recently developed a helper virus-free packaging system for HSV-1 vectors that addresses many of the current concerns about the vector system. In this application, the investigators describe experiments to test two hypotheses: The first hypothesis is that a further reduction in side effects of the vector system can be obtained by mutating specific components of the HSV-1 particle. The second hypothesis is that improved stability of long-term expression and improved accuracy of cell type-specific expression can be obtained by further reducing specific side effects of the vector system and by improving the structure of the vectors. These studies are designed to develop HSV-1 vector systems that cause minimal side effects and support stable long-term expression. Achieving these goals would represent meaningful progress towards the development of a HSV-1 vector system that might potentially be considered for human gene therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034025-04
Application #
2891974
Study Section
Special Emphasis Panel (ZRG1-NLS-3 (01))
Program Officer
Murphy, Diane
Project Start
1996-09-30
Project End
2001-07-31
Budget Start
1999-08-01
Budget End
2001-07-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
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