Related Experiment Videos
The antiprogestin-dependent GeneSwitch system for regulated gene therapy
1Valentis, Inc., 863A Mitten Road, Burlingame, CA 94010, USA. jeffnordstrom@advisys.net
Steroids
|December 12, 2003
Summary
A novel antiprogestin-controlled GeneSwitch system enables muscle-specific erythropoietin (EPO) expression in rodents. This gene therapy approach, regulated by mifepristone, offers a promising treatment for anemia.
Area of Science:
- Molecular Biology
- Gene Therapy
- Endocrinology
Background:
- Antiprogestin-controlled gene regulation systems utilize modified progesterone receptor ligand-binding domains (PR-LBDdelta19).
- These systems enable antiprogestin-inducible transcription factor activity for transgene expression.
Purpose of the Study:
- To design and evaluate a plasmid-based, muscle-specific GeneSwitch system for regulated erythropoietin (EPO) expression.
- To assess the efficacy and duration of mifepristone-controlled EPO production in vivo.
Main Methods:
- Development of a muscle-specific GeneSwitch system using a modified PR-LBD.
- Delivery of the system to skeletal muscle via electroporation in mice and rats.
- Oral administration of mifepristone (MFP) to regulate transgene expression and biological response.
Main Results:
- The GeneSwitch system successfully regulated EPO expression in a mifepristone-dependent manner.
- Effective regulation was achieved at low doses of MFP, with sustained biological responses (hematocrit changes) for over 6 months.
- The system demonstrated potential for long-lasting, inducible gene therapy.
Conclusions:
- The plasmid-based, antiprogestin-inducible EPO/GeneSwitch system is a viable tool for gene regulation in skeletal muscle.
- This system offers a convenient and effective approach for gene-based therapy, particularly for anemia treatment.