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Drug inducible transgene expression in brain using a herpes simplex virus vector
T Oligino1, P L Poliani, Y Wang
1Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, PA 15261, USA.
Gene Therapy
|June 6, 1998
Summary
This study developed a novel herpes simplex virus (HSV) vector for controlled gene expression in the central nervous system (CNS). The RU486 system effectively regulated transgene expression in vitro and in vivo, offering a precise on/off switch for gene therapy applications.
Area of Science:
- Neuroscience
- Molecular Biology
- Gene Therapy
Background:
- Regulatable transgene expression is crucial for gene therapy targeting central nervous system (CNS) diseases.
- Herpes simplex virus (HSV) vectors are promising for CNS gene delivery.
Purpose of the Study:
- To create a regulatable gene expression system for HSV vectors in the CNS.
- To demonstrate the efficacy of a RU486-inducible system for controlling transgene expression in the brain.
Main Methods:
- Developed a replication-incompetent genomic HSV vector with a RU486-inducible transactivator and lacZ reporter gene.
- Administered RU486 in vitro and in vivo to regulate reporter gene expression.
- Inoculated the vector into the rat hippocampus and assessed expression following RU486 administration.
Main Results:
- Reporter gene expression was effectively regulated by RU486 in cell culture and in vivo.
- Half-maximal expression in cell culture was achieved at 10(-8) M RU486 within 24 hours.
- Intraperitoneal administration of RU486 increased transgene expression 150-fold in the rat hippocampus.
Conclusions:
- The RU486 system provides a tight on/off switch for transgene expression.
- This inducible system is effective for regulating gene expression delivered to the brain via HSV vectors.
- This technology holds potential for precise control in CNS gene therapy.