• design safe SIN (self inactivating) retroviral and lentiviral COL7A1 vectors
• test different promoters and viral envelope proteins for efficient gene delivery and expression in cultured primary keratinocytes and fibroblasts
• study proliferative capacity of transduced cells, assess long-term expression of recombinant collagen VII and analyse proviral integration sites for deleterious effects
• analyse synthesis, folding and secretion of recombinant collagen VII and its ability to form anchoring fibres in skin equivalent model and in skin grafts on mice
• construct and produce vectors with full traceability to Good Laboratory Practice (GLP) standards.

Step 2

• cell clones producing the highest titres of the selected SIN retroviral or lentiviral vector (mini-cell bank) will be expanded, evaluated and a unique GMP master cell bank (MCB) established
• MCB will be tested for safety, to be used in production of clinical grade viral particles.

Step 3

• pilot clinical trial (Phase I/II) of genetically corrected autologous cell grafts over a limited skin surface in 6 selected patients (3 with detectable COL 7 protein and 3 without).
• safety, ethical and legal requirements will be adhered to throughout.
• Will serve as proof-of-principle for treatment of RDEB and as a model for the treatment of genetic disorders by ex vivo gene therapy.

Partner organisations

INSERM U563, Department of functional genetics of epithelial diseases (France) Project Co-ordinator

School of Life Sciences, Swiss Federal Institute of Technology (Switzerland)

Department of Dermatology, Necker Hospital (France)

Généthon (France)

Centre for Cutaneous Research (UK)

St John’s Institute of Dermatology (UK)

Max-Planck-Institute fur Biochemie (Germany)

DEBRA Europe (UK based)