Xenome
Xenotransplantion studies
The ultimate goal of our consortium is to generate the necessary data to allow xenotransplantation to progress towards its initial clinical phase. The data generated during this project will encompass both efficacy and safety aspects of xenotransplantation. Tools that will be used to reach this ambitious objective encompass state-of-the-art biomolecular technologies and in vivo models. XENOME aims to produce a “super-engineered” pig, i.e. a pig with a newly generated genotype that will improve the efficacy and safety profile of xenotransplantation. Assessments of efficacy will first take advantage of existing pig lines expressing human complement regulators, thrombomodulin (TM) and knock-out for α-Gal transferase (α-GalT KO). Using the most suitable background, further engineering will eliminate one or more PERV sequences. Additional transgenes, such as HO-1, CD39 and other molecules able to control immune responses, endothelial cell activation and subsequent microangiopathy, will be added. The ultimate pig strain will thus combine the already available background with novel molecules exhibiting anti-inflammatory, anticoagulant and immunosuppressive properties. In addition, an effective immunosuppression regimen will be defined and new pharmaceutical agents will be tested. A strong safety framework will also be established that may allow, at some stage, progression of xenotransplantation into the clinic. This will involve development of technologies enabling the timely diagnosis of infection, design of a safety plan for an efficacious containment of an untoward infectious event, breeding of a herd of “clean” source pigs, inactivation of PERV sequences and provide safety-related data deriving from long-term in vivo studies in primate xenograft recipients. Finally, the project will also provide a strong ethical, social (especially regarding public communication) and regulatory framework for xenotransplantation research (and possibly clinical application).
GATC’s task:
Using the LAM-PCR method the genomic position of the PERV element can be identified in the pig lineages used in the study. The presence of truncated (Solo-LTR) or full length PERV elements will be verified by PCR.
Participating partners:
- Azienda Ospedaliera di Padova, Italy
- Biomedical Law Centre, Portugal
- Consorzio per l’incremento Zootecnico srl, Italy
- Consorzio per la Ricerca sul trapianto d’Organi, Italy
- Corline Systems AB, Sweden
- Fundação Calouste Gulbenkian, Portugal
- GATC Biotech AG, Germany
- Hanover Medical School, Germany
- Institut de Transplantation et de Recherche en Transplantation – Université de Nantes, France
- Institute for Animal Breeding, Federal Agricultural Research Centre, Mariensee, Germany
- Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Czech Republic
- Leiden University Medical Centre, Netherlands
- Medical University of Vienna, Austria
- Universidad del Pais Vasco, Spain
- Università Cattolica S.C. Milano, Italy
- Université Catholique de Louvain, Belgium
- University College London, United Kingdom
- University of Cambridge, United Kingdom
- University of Glasgow, United Kingdom
- University of Milan, Italy
- University of Padua, Italy
