Research program

GENEGRAFT is a translational project, which aims to achieve a first phase I/II clinical trial for ex vivo gene therapy in 3 RDEB patients. The therapeutic principle is the transplantation of skin equivalents genetically corrected with a safe SIN retroviral vector, which have recently obtained the orphan drug designation from the European Medicines Agency. This trial will address the safety of the technique and its potential to lead to clinical benefit.


This pilot clinical trial involves a limited number of patients since it is a phase Ib clinical trial for a rare condition which aim to demonstrate first the feasibility and safety of the procedure and to a lesser extent the efficacy of the treatment.






The GENEGRAFT project aims at using a new Investigational medicinal product which obtained recently the Orphan drug designation EU/3/09/630) by the E.M.A (European Medicines Agency) to translate these pre-clinical results into a phase I/II clinical trial.



The GENEGRAFT project will involve the transfer and the adaptation from the research laboratory to the Gene therapy Centre, of the entire experimental procedure for genetic correction of RDEB using transplantation of skin equivalents onto patients.





  • Identify 3 patients with optimal clinical and biological features for a first clinical trial and satisfactory keratinocyte proliferative capacities.


  • Develop a method for high titre production of the Amphotropic SIN COL7A1 retroviral vector and the establishment of a SIN COL7A1 producer cell line. A method for concentration will be developed and functional validation of the viral batch will be performed. A clinical grade SIN COL7A1 vector will be produced, characterized and released.


  • Transfer and adapt the protocols used to generate genetically corrected skin equivalents from pre-clinical to GMP standards. This will  also include to generate a clinical grade cell bank of selected patients under GMP conditions.
  • Investigate the safety and the lack of toxicity of the approach. Safety assessment will include demonstration of absence of tumorigenicity of the approach during the preclinical development and the validation of quality control tests (provirus integrity, detection of RCR and other infectious agents).
  • Implement and conduct the clinical trial. Regulatory and ethical issues will be assess prior to implement of the trial.
  • Monitor the graft and the patient during the clinical trial. The tests will include the surveillance of the immune response towards type VII collagen after the grafting and the establishment of the integration site pattern prior to grafting and after 6 months of follow-up.