Silencing of tgf-beta receptor type ii expression by sirna

C - Chemistry – Metallurgy – 07 – H

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C07H 21/02 (2006.01) A61K 31/7105 (2006.01) A61K 31/713 (2006.01) A61P 9/10 (2006.01) A61P 17/02 (2006.01) A61P 27/06 (2006.01) C12N 15/12 (2006.01) C12N 15/18 (2006.01)

Patent

CA 2535516

The present application is directed to siRNA-based silencing of the type II receptor of TGF.beta.. siRNAs that target this receptor abrogate the receptor protein and transcript, TGF.beta.-mediated processes such as fibronectin assembly and cell migration also are inhibited and the molecules of the invention are efficacious in reducing the inflammatory response and matrix deposition. These findings show that siRNAs can be successfully delivered both in vitro and in vivo to regulate the TGF.beta. type II receptor level and modulate wound response. Methods and compositions exploiting the findings of the present invention have a wide-ranging application, extending from treatment of disorders of the eye to other organs and tissues throughout the body.

La présente invention concerne l'extinction du récepteur TGF.beta. de type II par des ARNsi. Des ARNsi ciblant ce récepteur suppriment la protéine et le transcrit du récepteur ; des processus médiés par TGF.beta., tels que l'assemblage de fibronectines et la migration cellulaire, sont également inhibés et les molécules de cette invention sont efficaces pour réduire la réponse inflammatoire et le dépôt de matrice. Ces découvertes montrent que des ARNsi peuvent être administrés avec succès à la fois in vitro et in vivo pour réguler le niveau du récepteur TGF.beta. de type II et moduler la réaction à une blessure. Des méthodes et compositions tirant profit de ces découvertes trouvent une large application dans le traitement de troubles, allant de l'oeil à d'autres organes et tissus à travers le corps.

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