Abstract
Dystrophic epidermolysis bullosa (DEB) is a family of inherited mechano-bullous disorders that are caused by mutations in the type VII collagen gene and for which ex vivo gene therapy has been considered. To develop a simpler approach for treating DEB, we evaluated the feasibility of protein-based therapy by intradermally injecting human recombinant type VII collagen into mouse skin and a DEB human skin equivalent transplanted onto mice. The injected collagen localized to the basement membrane zone of both types of tissues, was organized into human anchoring fibril structures and reversed the features of DEB disease in the DEB skin equivalent.
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Acknowledgements
This work was supported by grants RO1 AR47981 (M.C.) and RO1 AR33625 (D.T.W.) from the US National Institutes of Health. We thank S. Tufa for technical support of immunoelectron microscopy.
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Supplementary information
Supplementary Fig. 1
Dose-dependent deposition of injected human type VII collagen at the mouse's BMZ. (PDF 203 kb)
Supplementary Fig. 2
Sustained incorporation of human type VII collagen at the BMZ of hairless immunocompetent mice after a single intradermal injection. (PDF 1266 kb)
Supplementary Fig. 3
Incorporation of subsequently injected type VII collagen into the mouse's BMZ regardless the presence of anti-type VII collagen antibodies. (PDF 1061 kb)
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Woodley, D., Keene, D., Atha, T. et al. Injection of recombinant human type VII collagen restores collagen function in dystrophic epidermolysis bullosa. Nat Med 10, 693–695 (2004). https://doi.org/10.1038/nm1063
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DOI: https://doi.org/10.1038/nm1063
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