The purpose of this two-year programme is to push forward gene therapy for Recessive Dystrophic EB. To achieve this goal, six international groups with specific and complementary expertise have been selected.

Patients with Recessive Dystrophic EB suffer from a loss of adhesion between the epidermis and dermis, leading to severe skin blistering. This condition is caused by mutations in the type VII collagen gene (COL7A1) encoding a key component of the dermal-epidermal junction. People with Recessive Dystrophic EB have inherited a mutated copy from each of their parents.

In the majority of patients, COL7A1 mutations result in the absence of the production of type VII collagen protein. In contrast, their parents carry a normal and a mutated copy of COL7A1 and show no skin blistering. This suggests that 50% of normal type VII collagen is sufficient to maintain normal dermal-epidermal adhesion. Therefore, re-expression of type VII collagen from only one normal copy of the gene should correct the disease.

Skin cells can be easily expanded in the laboratory, and grafted back on to patients. Should genetic correction of patients' skin cells be achieved in culture, these cells could then be used to graft severely affected areas. Thus the aim of the programme is to successfully restore long-term expression of type VII collagen in epidermal cells from people with Recessive Dystrophic EB in culture, suitable for grafting.

To achieve this goal, several approaches will be used in parallel aiming at transferring a normal copy of COL7A1 into the target cells. One approach will use highly efficient and safe new viral vectors (delivery mechanisms) for random integration of a short version of the gene (cDNA) into patients' cell chromosomes.

A second approach will use targeted integration of COL7A1 cDNA into these cells. A third approach will involve the transfer of mammalian artificial chromosomes ("minichromosome") carrying a functional copy of the entire type VII collagen gene to patients' cells in culture. After confirmation that the corrected cells produce a functional type VII collagen protein, epithelial sheets suitable for grafting will be grown in culture for possible pre-clinical trials. Legislative and regulatory issues relevant to gene therapy in humans will be strictly followed. Treatment of patients with genetically corrected skin cells in selected areas, such as the hands and the feet, should prevent fusion of the digits and the development of skin cancer in these areas.