BP180 gene delivery in junctional epidermolysis bullosa

• Published in: Gene therapy Vol. 6; no. 1; pp. 42 - 47
• Main Authors: SEITZ, C. S, GIUDICE, G. J, BALDING, S. D, MARINKOVICH, M. P, KHAVARI, P. A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 1999
• Subjects: Animals; Autoantigens - genetics; Autoantigens - metabolism; Biological and medical sciences; Biotechnology; Carrier Proteins; Cell Adhesion; Cells, Cultured; Collagen; Collagen Type XVII; Cytoskeletal Proteins; Dystonin; Epidermolysis Bullosa, Junctional - therapy; Fundamental and applied biological sciences. Psychology; Gene therapy; Gene Transfer Techniques; Genetic Therapy - methods; Genetic Vectors - genetics; Health. Pharmaceutical industry; Industrial applications and implications. Economical aspects; Keratinocytes - metabolism; Mice; Mice, SCID; Nerve Tissue Proteins; Non-Fibrillar Collagens; Retroviridae - genetics; Skin - metabolism; Bullous dermatosis; Immunopathology; Animal model; Skin disease; Epidermolysis bullosa; Glycoprotein; Rodentia; Autoimmune disease; Gene expression; Adhesion; Genetic disease; Genetic transfer; Vertebrata; Mammalia; Gene; Mouse; Collagen; Keratinocyte; Gene therapy
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3300809

Epidermolysis bullosa (EB) comprises a family of inherited blistering skin diseases for which current therapy is only palliative. Junctional EB (JEB) involves dissociation of the dermal-epidermal junction and results from mutations in a number of genes that encode vital structural proteins, including BP180 (type XVII collagen/BPAG2). In order to develop a model of corrective gene delivery for JEB, we produced a retroviral expression vector for wild-type human BP180 and used it to restore BP180 protein expression to primary keratinocytes from BP180-negative patients with generalized atrophic JEB. Restoration of full-length BP180 protein expression was associated with adhesion parameter normalization of primary JEB keratinocytes in vitro. These cells were then used to regenerate human skin on immune-deficient mice. BP180 gene-transduced tissue demonstrated restoration of BP180 gene expression at the dermal-epidermal junction in vivo while untransduced regenerated JEB skin entirely lacked BP180 expression. These findings provide a basis for future efforts to achieve gene delivery in human EB skin tissue.