BP180 gene delivery in junctional epidermolysis bullosa

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 mut ations in a number of genes that encode vital structural proteins, includin g BP180 (type XVII collagen/BPAG2). In order to develop a model of correcti ve gene delivery for JEB, we produced a retroviral expression vector for wi ld-type human BP180 and used it to restore BP180 protein expression to prim ary keratinocytes from BP180-negative patients with generalized atrophic JE B. Restoration of full-length BP180 protein expression was associated with adhesion parameter normalization of primary JEB keratinocytes in vitro. The se cells were then used to regenerate human skin on immune-deficient mice. BP180 gene-transduced tissue demonstrated restoration of BP180 gene express ion 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.