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Valproic acid enhances gene expression from viral gene transfer vectors
Shongshan Fan1, Casey A Maguire, Servio H Ramirez
1Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Ave., Box 672 (Room 3-9609), Rochester, NY 14642, USA.
Journal of Virological Methods
|March 2, 2005
Summary
Valproic acid (VPA), an epilepsy drug, boosts and extends gene expression from viral vectors. This histone deacetylase inhibitor (HDACi) offers a safer alternative for enhancing gene transfer efficacy in various cell types and in vivo.
Area of Science:
- Molecular Biology
- Pharmacology
- Gene Therapy
Background:
- Viral vectors are key for gene transfer but expression levels can be limiting.
- Pharmacologic agents can potentially enhance viral vector-mediated gene expression.
Purpose of the Study:
- To investigate the effect of valproic acid (VPA) on gene expression mediated by viral vectors.
- To explore VPA's potential as an enhancer for gene transfer applications.
Main Methods:
- Cells and mice were transduced with various viral vectors (adenovirus, AAV, herpesvirus).
- Valproic acid (VPA) was administered to assess its impact on transgene expression.
- Histone deacetylase inhibition (HDACi) mechanism was investigated.
- Cytotoxicity of VPA was compared to Trichostatin A (TSA).
Main Results:
- VPA significantly enhanced and prolonged exogenous gene expression across diverse cell types.
- Adenovirally-vectored gene expression was increased in vivo in mice treated with VPA.
- VPA's effects are linked to its function as a histone deacetylase inhibitor (HDACi).
- VPA demonstrated lower cytotoxicity compared to TSA.
Conclusions:
- Valproic acid (VPA) is a potent enhancer of viral vector-mediated gene transfer.
- VPA's HDAC inhibitory activity contributes to increased and sustained transgene expression.
- VPA represents a promising, safer alternative for improving gene therapy efficacy.