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Engineering of the porcine genome for xenotransplantation studies in primates: a step towards clinical application

Objective

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).

Call for proposal

FP6-2005-LIFESCIHEALTH-6
See other projects for this call

Funding Scheme

IP - Integrated Project

Coordinator

AZIENDA OSPEDALIERA DI PADOVA
Address
Via Giustiniani 2
Padova
Italy

Participants (25)

CHALEX RESEARCH LTD
United Kingdom
Address
Chalex House, Priory Road, St Marychurch
Torquay
CENTRE HOSPITALO-UNIVERSITAIRE DE NANTES- ITERT
France
Address
Boulevard Jean Monnet, 30
Nantes
UNIVERSIDAD DEL PAIS VASCO
Spain
Address
B(o) Sarriena, S/n
Leioa (Bizkaia)
MEDICAL UNIVERSITY OF VIENNA
Austria
Address
Spitalglasse 23
Vienna
UNIVERSITY COLLEGE LONDON
United Kingdom
Address
Gower Street
London
INSTITUTE FOR ANIMAL BREEDING, FEDERAL AGRICULTURAL RESEARCH CENTRE
Germany
Address
Hoeltystr. 10, Mariensee
Neustadt
UNIVERSITY OF GLASGOW
United Kingdom
Address
University Avenue
Glasgow
CONSORZIO PER L'INCREMENTO ZOOTECNICO SRL'
Italy
Address
Via Maremmana 17 A/c
La Serra Di San Miniato (Pi)
INSTITUTE OF MOLECULAR GENETICS, ACADEMY OF SCIENCES OF THE CZECH REPUBLIC
Czechia
Address
Flemingovo Namesti 2
Prague
MEDIZINISCHE HOCHSCHULE HANNOVER (HANNOVER MEDICAL SCHOOL)
Germany
Address
Carl-neuberg-str. 1
30623 Hannover
UNIVERSITY OF PADUA
Italy
Address
Via 8 Febbraio, 2
Padua
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
United Kingdom
Address
The Ed Adrian Building, Forvie Site, Robinson Way
Cambridge
GATC BIOTECH AG
Germany
Address
Jakob-stadler-platz 7
Konstanz
CONSORZIO PER LA RICERCA SUL TRAPIANTO D'ORGANI', TESSUTI, CELLULE E MEDICINA RIGENERATIVA
Italy
Address
Passaggio Luigi Gaudenzio 1
Padova
CORLINE SYSTEMS AB
Sweden
Address
Lefflersgatan 5
Uppsala
BIOMEDICAL LAW CENTRE
Portugal
Address
Faculty Of Law, University Of Coimbra
Coimbra
FUNDACAO CALOUSTE GULBENKIAN
Portugal
Address
Avenida De Berna 45-A
Lisboa
LEIDEN UNIVERSITY MEDICAL CENTRE
Netherlands
Address
Albinusdreef 2, 2333 Za
9600 Leiden
GLASGOW CALEDONIAN UNIVERSITY
United Kingdom
Address
70 Cowcaddens Road
Glasgow
COMMISSARIAT À L'ÉNERGIE ATOMIQUE ET AUX ÉNERGIES ALTERNATIVES
France
Address
25, Rue Leblanc, Bâtiment Le Ponant D
Paris
FRIEDRICH-LOEFFLER-INSTITUT, FEDERAL RESEARCH INSTITUTE FOR ANIMAL HEALTH
Germany
Address
Südufer, 10
Greifswald, Insel Riems
AVANTEA SRL
Italy
Address
Via Cabrini, 12
Cremona
UNIVERSITA CATTOLICA DEL SACRO CUORE
Italy
Address
Largo Gemelli 1
Milano
UNIVERSITA DEGLI STUDI DI MILANO-BICOCCA
Italy
Address
Piazza Dell'ateneo Nuovo, 1'
Milan
UNIVERSITE CATHOLIQUE DE LOUVAIN
Belgium
Address
Place De L'universite, 1'
Ottignies Louvain-la-neuve