Gene therapy: pursuing restoration of dermal adhesion in recessive dystrophic epidermolysis bullosa.

[dystrophic epidermolysis bullosa]

The replacement of a defective gene with a fully functional copy is the goal of the most basic gene therapy . Recessive dystrophic epidermolysis bullosa (RDEB ) is characterised by a lack of adhesion of the epidermis to the dermis . It is an ideal target for gene therapy as all variants of hereditary RDEB are caused by mutations in a single gene , COL 7 A 1 , coding for type VII collagen , a key component of anchoring fibrils that secure attachment of the epidermis to the dermis . RDEB is one of the most severe variants in the epidermolysis bullosa (EB ) group of heritable skin diseases . Epidermolysis bullosa is defined by chronic fragility and blistering of the skin and mucous membranes due to mutations in the genes responsible for production of the basement membrane proteins . This condition has a high personal , medical and socio-economic impact . People with RDEB require a broad spectrum of medications and specialised care . Due to this being a systemic condition , most research focus is in the area of gene therapy . Recently , preclinical works have begun to show promise . They focus on the virally mediated ex vivo correction of autologous epithelium . These corrected cells are then to be expanded and grafted onto the patient following the lead of the first successful gene therapy in dermatology being a grafting of corrected tissue for junctional EB treatment . Current progress , outstanding challenges and future directions in translating these approaches in clinics are reviewed in this article .