Joint Research Program

Joint Research Program

GENEGRAFT proposes an innovative solution by exploiting partners’ high scientific and technical development in ex vivo gene therapy to establish a clinical trial model for RDEB treatment




We therefore proposed the following innovative approach comprising 9 synergistic workpackages that will allow the successful achievement of Genegraft objectives.



WP1: Patient recruitment and selection :

Aims at identifying 3 patients with RDEB from two large international cohorts of patients, with optimal clinical and biological features for a first clinical trial  and satisfactory keratinocyte proliferative capacities.


WP2: Production of pilot and clinical grade viral batch and validation:

A method for high titre production of the Amphotropic SIN COL7A1 retroviral vector will be developed and a SIN COL7A1 producer cell line will be established. 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 .


WP3: Transfer and adaptation of the know how and protocols from research to GMP standards:

Aims at establishing Standard Operating Procedures for GMP protocols for cell culture, efficient transduction of primary RDEB keratinocytes and fibroblasts and large scale skin equivalent production. A clinical-grade cell bank of primary keratinocytes and fibroblasts of selected patients who are tolerant towards type VII collagen will also be established.


WP4: Safety considerations and toxicology:

Aims at demonstrating of the safety of the approach. Therefore all the investigations described in this WP aim at verifying that no adverse effect occurs during this trial. Safety assessment will include demonstration of absence of tumorigenicity of the approach during the preclinical development and the validation of quality control tests. These tests include the demonstration of the provirus integrity and the integration site analysis. Further tests to monitor the graft and the patient will performed during the clinical trial tests will include the quality control of the graft prior to the grafting (provirus integrity, detection of RCR and other infectious agents), 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.


WP5: Regulatory and ethical requirements:

Aims to fulfil all the regulatory and ethical requirements to obtain clinical trial authorisation. The clinical and non clinical regulatory documents will be completed and clinical trial authorization will be requested from the AFSSAPS. A pharmaceutical industry will be identified for marketing authorisation application (MAA).


WP6: Implementation of the clinical trial:

Aims to obtain the accreditation of the Gene Therapy Centre to conduct the trial (M6.1) and to implement the clinical trial according to the authorized protocol leading to the opening of the site.


WP7: Clinical trial conduct:

Aims at treating a first patient using clinical grade skin equivalents grafts genetically corrected with a COL7A1 encoding retroviral vector (orphan drug designation EU/3/09/630) and to monitor the tolerance and the effectiveness of this graft. A total of 3 patients could be grafted and their outcome will be monitored. A study final report will be prepared and provided to the regulatory agencies.

WP8: Management of the consortium:

Aims to create a solid and flexible management structure that will take into account the complexity of developing tools and conditions to progress in studying RDEB and related ethical issues. Management activities support the execution of the project as a whole and will be focused on establishing, optimising and implementing the project and the infrastructure for achieving the project goals. Three different management levels are offered: coordination of the whole project, progress monitoring and coordination at workpackage level. Partner 1a, INSERM, will be in charge of the scientific management supported by Partner 6, Inserm Transfert, focusing on legal, financial, resources, reporting, knowledge, intellectual property and ethical issues.


WP9: Dissemination:

This workpackage aims to disseminate the results of Genegraft and educate health care professionals and patients using the Debra network, in collaboration with patients’ organisations. Promote integration and exchanges within and outside the Genegraft community. And finally, manage intellectual property issues arising from the project.