Abstract
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 acheive gene delivery in human EB skin tissue.
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Seitz, C., Giudice, G., Balding, S. et al. BP180 gene delivery in junctional epidermolysis bullosa. Gene Ther 6, 42–47 (1999). https://doi.org/10.1038/sj.gt.3300809
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DOI: https://doi.org/10.1038/sj.gt.3300809
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