The Potential of Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa

K.S. Subramaniam; M.N. Antoniou; J.A. McGrath; S.M. Lwin


The British Journal of Dermatology. 2022;186(4):609-619. 

In This Article

Why is Gene Therapy a Promising Treatment for Inherited Skin Diseases Such as Recessive Dystrophic Epidermolysis Bullosa?

Advances in genomic biotechnology, along with the cloning of COL7A1 in 1991,[21–24] are foundational to the development of gene therapy approaches for DEB.[25] Historical milestones of advances in gene therapy relevant to RDEB are summarized in Figure 2. Across the spectrum of individuals with RDEB, there is an inverse correlation between the level of C7 expression at the BMZ and clinical severity.[26] In principle, by replacing or correcting the defective COL7A1 gene, expression and function of the affected C7 protein and subsequently AFs can be restored, thereby improving the dermal–epidermal adherence and skin resistance against mechanical trauma.[27] This will then lead to an improvement in wound healing, potentially preventing scarring and the development of SCCs, especially if treated in children. As C7 protein is produced by both keratinocytes and fibroblasts, both cell types can be isolated and cultured from a skin biopsy of a patient with RDEB. The isolated cells subsequently undergo genetic manipulation to produce a new population of autologous gene-corrected or modified cells containing functional COL7A1, which are then returned to the patient in the form of epithelial (keratinocytes) or skin equivalent (keratinocytes and fibroblasts) grafts, or intradermal (fibroblasts or other forms of stem cells) or intravenous (fibroblasts or other forms of stem cells) injections (although systemic gene therapy has yet to enter human trials), depending on the cell target.[25,28]

Figure 2.

Historical milestones of advances in gene therapy relevant to recessive dystrophic epidermolysis bullosa (RDEB). COL7A1, collagen type VII alpha 1 chain gene; JEB, junctional epidermolysis bullosa; MSC, mesenchymal stromal cell; PTC, premature termination codon; TALENs, transcription activator-like effector nucleases. Created using bioRENDER (