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Letter
Nature Genetics  32, 670 - 675 (2002)
Published online: 11 November 2002; | doi:10.1038/ng1041

Restoration of type VII collagen expression and function in dystrophic epidermolysis bullosa

Mei Chen1, Noriyuki Kasahara2, Douglas R. Keene3, Lawrence Chan4, Warren K. Hoeffler5, Deborah Finlay5, Maria Barcova2, Paula M. Cannon2, Constance Mazurek2 & David T. Woodley1

1  Department of Medicine, Division of Dermatology, University of Southern California, CRL 204, 1303 Mission Road, Los Angeles, California 90033, USA.

2  Departments of Pathology and Biochemistry, University of Southern California, CRL 204, 1303 Mission Road, Los Angeles, California 90033, USA.

3  Shriners Hospital for Children, Portland, Oregon, USA.

4  Department of Dermatology, Northwestern University, Chicago, Illinois, USA.

5  Xgene Corporation, San Carlos, California, USA.

Correspondence should be addressed to Mei Chen chenm@hsc.usc.edu
Dystrophic epidermolysis bullosa (DEB) is a family of inherited mechano-bullous disorders caused by mutations in the human type VII collagen gene (COL7A1). Individuals with DEB lack type VII collagen and anchoring fibrils, structures that attach epidermis and dermis. The current lack of treatment for DEB is an impetus to develop gene therapy strategies that efficiently transfer and stably express genes delivered to skin cells in vivo. In this study, we delivered and expressed full-length type VII collagen using a self-inactivating minimal lentivirus-based vector. Transduction of lentiviral vectors containing the COL7A1 transgene into recessive DEB (RDEB) keratinocytes and fibroblasts (in which type VII collagen was absent) resulted in persistent synthesis and secretion of type VII collagen. Unlike RDEB parent cells, the gene-corrected cells had normal morphology, proliferative potential, matrix attachment and motility. We used these gene-corrected cells to regenerate human skin on immune-deficient mice. Human skin regenerated by gene-corrected RDEB cells had restored expression of type VII collagen and formation of anchoring fibrils at the dermal−epidermal junction in vivo. These studies demonstrate that it is possible to restore type VII collagen gene expression in RDEB skin in vivo.


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REFERENCE
Regeneration of Mammalian Skin
Nature Encyclopaedia of Life Sciences

REVIEWS
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RESEARCH
Dystrophic Epidermolysis Bullosa
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Nature Medicine Article (01 Oct 2002)
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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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