Antisense modulation of expression of tumor necrosis factor receptor-associated factors (TRAFs)

Abstract

Compositions and methods are provided for modulating the expression of tumor necrosis factor receptor-assocaited factor (TRAF). Antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding TRAF are preferred. Methods of using these compounds for modulation of TRAF expression and for treatment of diseases associated with expression of TRAF are provided.

What is claimed is:  
     
         1 . An antisense compound 8 to 30 nucleotides in length targeted to a nucleic acid molecule encoding a human tumor necrosis factor receptor-associated factor, wherein said antisense compound inhibits the expression of human tumor necrosis factor receptor-associated factor.  
     
     
         2 . The antisense compound of  claim 1  which is an antisense oligonucleotide.  
     
     
         3 . The antisense oligonucleotide of  claim 2  which comprises at least one modified internucleoside linkage.  
     
     
         4 . The antisense oligonucleotide of  claim 3  wherein the modified internucleoside linkage is a phosphorothioate linkage.  
     
     
         5 . The antisense oligonucleotide of  claim 2  which comprises at least one modified sugar moiety.  
     
     
         6 . The antisense oligonucleotide of  claim 5  wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.  
     
     
         7 . The antisense oligonucleotide of  claim 2  which comprises at least one modified nucleobase.  
     
     
         8 . The antisense oligonucleotide of  claim 7  wherein the modified nucleobase is a 5-methylcytosine.  
     
     
         9 . The antisense compound of  claim 1  which is a chimeric oligonucleotide.  
     
     
         10 . The antisense compound of  claim 1  wherein the human TRAF is TRAF-2 or TRAF-6.  
     
     
         11 . A pharmaceutical composition comprising the antisense compound of  claim 1  and a pharmaceutically acceptable carrier or diluent.  
     
     
         12 . The pharmaceutical composition of  claim 11  comprising a colloidal dispersion system.  
     
     
         13 . The pharmaceutical composition of  claim 11  wherein the antisense compound is an antisense oligonucleotide.  
     
     
         14 . A method of inhibiting the expression of tumor necrosis factor receptor-associated factor in human cells or tissues comprising contacting said cells or tissues with the antisense compound of  claim 1  so that expression of tumor necrosis factor receptor-associated factor is inhibited.  
     
     
         15 . A method of reducing jun kinase activation in cells or tissues by tumor necrosis factor-α comprising contacting said cells or tissues with an antisense compound targeted to TRAF-2.  
     
     
         16 . A method of reducing jun kinase activation in cells or tissues comprising contacting said cells or tissues with an antisense compound targeted to TRAF-6.  
     
     
         17 . A method of reducing E-selectin expression in cells or tissues comprising contacting said cells or tissues with an antisense compound targeted to TRAF-2 or TRAF-6.