Abstract Epidermolysis bullosa (EB) is a genetic disorder that stems from defects at 16 genetic loci. Four main EB subtypes are recognized in the clinic. All EB patients exhibit skin lesions and blisters due to defective attachment of the epidermis to the dermis at the dermo–epidermal junction (DEJ). Genetic deficits in sustaining basal keratinocyte structural integrity result in either epidermolysis bullosa simplex (EBS) or Kindler epidermolysis bullosa (KEB). Mutations impairing the attachment of the basal keratinocyte to the underlying extracellular matrix (ECM) yield junctional epidermolysis bullosa (JEB). The last subtype, dystrophic epidermolysis bullosa (DEB), manifests solely from defective alleles at the COL7A1 locus, encoding the collagen type VII α1 subunit that composes the anchoring fibrils to secure the dermis to the ECM. Modern EB treatments hold promise by aiming to deliver non-defective alleles to remediate any of the 16 genes lesioned in EB patients. In particular, genetically engineered, non-replicating, recombinant herpes simplex virus has been used to transduce wild-type COL7A1 alleles to the wounded skin of DEB patients. The unique histological features of EB pathophysiology make it especially well suited to gene therapy, as the skin’s accessible surface provides an ideal landscape for targeted, topical genetic interventions.
Pol et al. (Sun,) studied this question.