Advanced gene-editing strategy for epidermolysis bullosa simplex

Epidermolysis bullosa (EB) describes a spectrum of inherited disorders characterized by skin blistering and fragility.1 Subtypes of EB demonstrate a range of phenotypes, related to the underlying genetic cause and plane of cleavage within the skin, with some forms causing severe blistering and systemic manifestations of the disease. The most common type of EB, EB simplex (EBS), is usually inherited in an autosomal-dominant fashion and leads to loss of tissue integrity in the upper epidermis. The majority of EBS mutations create mutant keratin 14 (K14) or K5 proteins, which inhibit their normal heterodimerization and the assembly of intermediate filaments in basal keratinocytes, leading them to rupture with stress.