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Herpes simplex virus type 1 vector mediated gene transfer to muscle
J Huard1, W F Goins, J C Glorioso
1Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, PA 15261, USA.
Gene Therapy
|August 1, 1995
Summary
Replication-defective Herpes simplex virus type 1 (HSV-1) vectors successfully transduced muscle cells in vitro and in vivo. This suggests potential for HSV-1 in muscle gene therapy applications.
Area of Science:
- Virology
- Molecular Biology
- Gene Therapy
Background:
- Herpes simplex virus type 1 (HSV-1) naturally establishes latent infections in neurons.
- Replication-defective viral mutants may persist as episomes in non-neuronal cells.
- Muscle tissue is a target for gene transfer applications.
Purpose of the Study:
- To evaluate the utility of a replication-defective HSV-1 vector for gene transfer into muscle cells.
- To assess transgene expression and persistence in muscle cells in vitro and in vivo.
Main Methods:
- A replication-defective HSV-1 vector (d120) expressing beta-galactosidase under the HCMV immediate-early promoter was constructed.
- The vector was used to infect cultured myoblasts and myotubes.
- Direct inoculation of mouse muscle fibers in vivo was performed.
Main Results:
- The d120 vector showed reduced cytotoxicity in myogenic cells.
- Transgene expression persisted for at least 8 days in cultured muscle cells.
- Significant transduction of muscle fibers was observed in newborn and adult mice.
Conclusions:
- Replication-defective HSV-1 vectors can efficiently transduce muscle cells.
- HSV-1 vectors demonstrate potential for gene delivery to muscle tissue.
- Myoblast differentiation does not impede HSV-1 vector entry or transgene expression.