Anticoagulant fusion protein anchored to cell membrane

Details Anticoagulant fusion protein anchored to cell membrane Anticoagulant fusion protein anchored to cell membrane

C - Chemistry, Metallurgy

12

N

C12N 15/62 (2006.01) A01K 67/027 (2006.01) C07K 14/705 (2006.01) C07K 14/73 (2006.01) C07K 14/74 (2006.01) C07K 14/81 (2006.01) C07K 14/815 (2006.01) C12N 9/64 (2006.01) C12N 15/00 (2006.01) C12N 15/85 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2285702

The invention relates to the inhibition of blood coagulation, especially during organ rejection, and in particular the inhibition of delayed vascular rejection. The invention provides anticoagulant proteins which are anchored to cell membranes. The anticoagulant function is preferably provided by heparin, antithrombin, hirudin, TFPI, tick anticoagulant peptide, or a snake venom factor. These anticoagulant proteins are preferably prevented from being constitutively expressed at the cell surface. In particular, expression at the cell surface is regulated according to cell activation, for instance by targeting the protein to a suitable secretory granule. Expression of these proteins renders cells, tissues and organs less vulnerable to rejection after transplantation (e.g. after xenotransplantation).

L'invention concerne l'inhibition de la coagulation sanguine, notamment pendant un rejet d'organe, et en particulier l'inhibition d'un rejet vasculaire retardé. L'invention concerne des protéines anticoagulantes ancrées dans des membranes cellulaires. De préférence, la fonction anticoagulante est conférée par l'héparine, l'antithrombine, l'hirudine, l'inhibiteur de voie du facteur tissulaire (TFPI), le peptide anticoagulant de la tique, ou le facteur du venin de serpent. De préférence, ces protéines anticoagulantes sont inhibées pour empêcher leur expression constitutive à la surface cellulaire. En particulier, l'expression à la surface cellulaire est régulée en fonction de l'activité cellulaire, par exemple par le ciblage de la protéine sur une granule sécrétoire convenable. L'expression desdites protéines fragilise les cellules, tissus et organes, qui deviennent vulnérables au rejet après transplantation (c'est-à-dire après une xénotransplantation).

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