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XENOME - Engineering of the porcine genome for xenotransplantation studies in primates: a step towards clinical application
Project
Project code: 37377
Contract period: 01.11.2006
- 30.04.2012
Budget: 9,876,546 Euro
Purpose of research: Applied research
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 xeno-transplantation. 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 a-Gal transferase. 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 immuno-suppression 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).
Section overview
Subjects
- Animal breeding
