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HSV vector-mediated transduction and GDNF secretion from adipose cells

Gene Therapy volume 12, pages 48–58 (2005)Cite this article

Abstract

The accessibility of adipose tissue and its ability to secrete various bioactive molecules suggest that adipose cells may be attractive targets for gene therapy applications. Here, we report the use of highly defective herpes simplex virus (HSV) vectors as suitable gene transfer agents for adipose cells in culture and fat tissue in animals. Using an in vitro model of human adipose differentiation, we first demonstrated that mature adipocytes and their precursor cells express the two principal HSV viral entry receptors HveA and HveC (nectin-1) and are efficiently transduced at a low multiplicity of infection by HSV-lacZ reporter gene and glial cell line-derived neurotrophic factor (GDNF) gene vectors. Extended expression of β-galactosidase and secretion of GDNF occurred in transduced fat tissue explants from rabbits. In vivo gene transfer to rabbit subcutaneous adipose tissue resulted in local GDNF expression for at least 2 months. These experiments establish the efficient transduction of adipose cells by HSV vectors and suggest that fat tissue may represent a useful site for HSV-mediated gene delivery with potential for therapeutic applications.

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Acknowledgements

We thank Dr Simon Watkins and Laura Sysco for photographic imaging of adipose tissue, Joan Nash for assistance with animal studies,Will Seifred for technical assistance and Drs Harry Blair and Veronica Garcia for the use of the CryoJane® Tape-Transfer System. We thank Dr Patricia Spear (Northwestern University) for kindly providing the CHO-HveA and CHO-HveC cell lines and Drs Gary Cohen and Roselyn Eisenberg (University of Pennsylvania) for providing the CK6, CK41 and R140 Abs. This work was supported by a grant from Valentis corporation. JF was recipient of a fellowship from the Fonds de la Recherche en Santé du Québec (FRSQ, Canada).

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  1. Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    J Fradette, D Wolfe, W F Goins, S Huang, R M Flanigan & J C Glorioso

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  1. J Fradette
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  2. D Wolfe
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Fradette, J., Wolfe, D., Goins, W. et al. HSV vector-mediated transduction and GDNF secretion from adipose cells. Gene Ther 12, 48–58 (2005). https://doi.org/10.1038/sj.gt.3302359

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