Epidermolysis bullosa (EB) is a genetic disorder typified by ulcerated skin blisters, open wounds, and bacterial infections of the wounds, inflicting significant pain on patients. Diverse gene mutations precipitate varying frequencies and severities of wound manifestations. The gravest forms of EB can necessitate up to four hours daily for wound care, demanding substantial caregiver support. Patients with EB consider ‘reducing the number and severity of wounds’ as the paramount treatment factor for enhancing their life quality.
The treatment for patients with EB is limited. The recent FDA approval of the first topical gene therapy, Vyjuvek, developed by Krystal Biotech, underscores the potential of gene therapies in this field. Nevertheless, a major constraint with the currently approved therapies is their reliance on viral vectors to deliver genetic material to cells, which often provoke strong immunogenic reactions. Furthermore, whilst gene therapy tackles the root of the disease, it does not address associated consequences, such as bacterial infections.
We propose to develop a gene-activated scaffold as a new generation bioactive dressing or implant for the treatment of EB. These multifunctional scaffolds mimic the structure of human skin while reducing bacterial infections and, most importantly, will deliver gene therapies to correct genes affected by the disease. The use of scaffold and non-viral vectors facilitates controlled, local delivery with minimal immunogenic reaction. Upon implantation, the patient’s own cells will migrate towards the scaffolds and become transfected with the nanoparticles containing the correcting genetic cargoes which encode for the specific proteins, which are affected in Dystrophic and Junctional EB.
A pivotal aspect of this research is to involve patients and carers in the governance, design and dissemination phases to ensure this technology is eventually translated to benefit those with chronic wound pain due to EB, and to allow patient input to influence our research strategy.