Methods of Gene Therapy for Treatment of Inherited Epidermolysis Bullosa

Abstract

Inherited epidermolysis bullosa (EB) is a heterogeneous group of rare genodermatoses with a high skin fragility manifested by the formation of destructive blisters and non-healing erosions on the skin and mucous membranes as a reaction to minor mechanical influences. There are three main types of EB: simple, junctional and dystrophic, each is caused by mutations in genes that encode epidermal, zones of the basement membrane or dermis proteins, respectively. The fourth type of EB is also described–hemidesmosomal or Kindler syndrome with impairments in kindlin-1 protein encoded by the FERMT1 gene. The existing ways to improve the living conditions of patients with EB are at different stages of development: some of them are already used in the clinic, while others are still under laboratory research. Various strategies are used, depending on the type of EB and the nature of mutation inheritance: from the functional gene replacement therapy based on the viral expression to the genome editing methods by programmable synthetic nucleases. The accumulated experience of allogeneic and autologous transplants of skin equivalents opens the prospect for using new approaches to functional gene and cell therapy ex vivo.