Silencing of tgf-beta receptor type II expression by sirna

Abstract

The present application is directed to siRNA-based silencing of the type II receptor of TGFβ. siRNAs that target this receptor abrogate the receptor protein and transcript, TGFβ-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 TGFβ 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.

1 - 11 . (canceled)  
     
     
         12 . An siRNA molecule that reduces expression of the TGFβ type II receptor, wherein the siRNA molecule is 19-25 base pairs in length and targets at least a portion of the coding sequence of a nucleic acid molecule comprising the nucleic acid sequence of SEQ ID NO:159.  
     
     
         13 . A composition comprising the siRNA molecule of  claim 12  and a pharmaceutically acceptable carrier.  
     
     
         14 . The composition of  claim 13 , further comprising a wound healing agent.  
     
     
         15 . A method for promoting wound healing in a mammal comprising administering a therapeutically effective amount of a composition comprising the siRNA molecule of  claim 12  to a mammal in need of treatment.  
     
     
         16 . A method for inhibiting fibrosis in a mammal comprising administering a therapeutically effective amount of a composition comprising the siRNA molecule of  claim 12  to a mammal in need of treatment.  
     
     
         17 . A method for inhibiting angiogenesis in a mammal comprising administering a therapeutically effective amount of a composition comprising the siRNA molecule of  claim 12  to a mammal in need of treatment.  
     
     
         18 . A method for preventing glaucoma in a mammal comprising administering to a mammal in need of treatment a therapeutically effective amount of a composition comprising the siRNA molecule of  claim 12 .  
     
     
         19 . A method of preventing restenosis in a mammal comprising administering to said mammal a therapeutically effective amount of a composition comprising the siRNA molecule of  claim 12 .  
     
     
         20 . A method of preventing or treating scarring in a mammal comprising administering to said mammal a therapeutically effective amount of a composition comprising the siRNA molecule of  claim 12.