Gene therapy for transplantation and inflammatory or...

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/55 (2006.01) A01K 67/027 (2006.01) A61K 31/70 (2006.01) A61K 35/12 (2006.01) A61K 38/46 (2006.01) A61K 48/00 (2006.01) A61L 33/00 (2006.01) C07K 14/705 (2006.01) C12N 5/10 (2006.01) C12N 9/14 (2006.01) C12N 15/85 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2216445

A method to render in particular endothelial cells capable of inhibiting platelet and leukocyte-mediated injury and inflammation is described, comprising genetically modifying the cells by inserting therein DNA encoding ATP diphosphohydrolase or an oxidation-resistant analog thereof, and expressing a protein having functional ATP diphosphodydrolase activity, such as the human CD39 protein, from the cells under cellular activating conditions, and corresponding cells, tissue or organs, non-human transgenic or somatic recombinant mammals, pharmaceutical compositions and prosthetic intravascular devices. The invention, which can be carried out in vivo, ex vivo or in vitro, has use in allogeneic or xenogeneic transplantation as well as in treating systemic or local inflammatory conditions characterized by platelet aggregation leading to thrombus formation.

L'invention concerne un procédé permettant en particulier de rendre les cellules endothéliales capables d'inhiber les lésions et les inflammations provoquées par les plaquettes et les leucocytes, consistant à modifier génétiquement des cellules en introduisant dans ces cellules un ADN codant pour l'ATP-diphosphohydrolyse ou pour un analogue de celle-ci résistant à l'oxydation et exprimant une protéine ayant l'activité d'une ATP-diphosphohydrolyse fonctionnelle telle que la protéine humaine CD39, dans des cellules placées dans des conditions d'activation cellulaire. L'invention concerne également les cellules correspondantes, des tissus, organes et mammifères non humains transgéniques ou somatiques issus d'une recombinaison ainsi que des compositions pharmaceutiques et des prothèses intravasculaires, obtenus en faisant appel au procédé de l'invention. L'invention, qui peut être mise en oeuvre in vivo, ex vivo ou in vitro, est utile pour les transplantations allogènes ou xénogènes, ainsi que pour traiter des inflammations générales ou locales caractérisées par une agrégation plaquettaire conduisant à la formation de thrombus.

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