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HSV vector-mediated transduction and GDNF secretion from adipose cells
J Fradette1, D Wolfe, W F Goins
1Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Gene Therapy
|October 8, 2004
Summary
Herpes simplex virus (HSV) vectors efficiently deliver genes to fat cells. This research shows HSV vectors can be used for gene therapy in adipose tissue, offering potential therapeutic applications.
Area of Science:
- Gene therapy
- Virology
- Adipose tissue biology
Background:
- Adipose tissue is accessible and secretes bioactive molecules, making it a potential target for gene therapy.
- Herpes simplex virus (HSV) vectors are being explored as gene transfer agents.
Purpose of the Study:
- To evaluate the efficacy of HSV vectors for gene transfer into adipose cells.
- To investigate the potential of adipose tissue as a site for HSV-mediated gene delivery.
Main Methods:
- Utilized an in vitro model of human adipose differentiation.
- Transduced mature adipocytes and precursor cells using HSV-lacZ and glial cell line-derived neurotrophic factor (GDNF) gene vectors.
- Administered in vivo gene transfer to rabbit subcutaneous adipose tissue.
Main Results:
- Mature adipocytes and precursor cells express HSV entry receptors HveA and HveC (nectin-1).
- Efficient transduction of adipose cells was achieved at a low multiplicity of infection.
- Extended expression of beta-galactosidase and secretion of GDNF were observed in rabbit fat tissue explants.
- In vivo gene transfer resulted in local GDNF expression for at least 2 months in rabbits.
Conclusions:
- HSV vectors are effective gene transfer agents for adipose cells in vitro and in vivo.
- Adipose tissue is a viable site for HSV-mediated gene delivery, with potential therapeutic applications.