Restoration of type VII collagen expression and function in dystrophic epidermolysis bullosa
| Autor: | Maria Barcova, Constance Mazurek, Paula M. Cannon, Warren K. Hoeffler, David T. Woodley, Douglas R. Keene, Mei Chen, Deborah Ruth Finlay, Lawrence S. Chan, Noriyuki Kasahara |
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| Rok vydání: | 2002 |
| Předmět: |
Keratinocytes
Collagen Type VII DNA Complementary Genetic enhancement Genetic Vectors Human skin Genes Recessive Biology Transfection Cell Line Dermis Cell Movement Anchoring fibrils Genetics medicine Cell Adhesion Humans Transgenes Cells Cultured integumentary system Epidermis (botany) Lentivirus Gene Transfer Techniques Genetic Therapy Fibroblasts Cell Transformation Viral Molecular biology Epidermolysis Bullosa Dystrophica Collagen type I alpha 1 medicine.anatomical_structure Epidermal Cells Cell culture Immunology Mutation Laminin Cell Division |
| Zdroj: | Nature genetics. 32(4) |
| ISSN: | 1061-4036 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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