Antisense modulation of interleukin 12 P35 subunit expression

Abstract

Compounds, compositions and methods are provided for modulating the expression of Interleukin 12 p35 subunit. The compositions comprise chemically modified antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Interleukin 12 p35 subunit. Methods of using these compounds for modulation of Interleukin 12 p35 subunit expression and for treatment of diseases associated with expression of Interleukin 12 p35 subunit are provided.

1 . A compound comprising a chemically modified antisense oligonucleotide compound 15 to 30 nucleobases in length targeted to an active site of a nucleic acid molecule encoding Interleukin 12 p35 subunit.  
     
     
         2 . The compound of  claim 1  comprising SEQ ID NO: 23, 24 or 44.  
     
     
         3 . The compound of  claim 1  further comprising at least one chemical modification selected from the group consisting of: a modified nucleobase, a substituted sugar moiety, a modified oligonucleotide backbone or a conjugate.  
     
     
         4 . The compound of  claim 3  further comprising a sense strand such that the antisense oligonucleotide is double stranded siRNA.  
     
     
         5 . The compound of  claim 3  comprising a chimeric oligonucleotide of 15 to 30 nucleobases in length targeted to a nucleic acid molecule encoding Interleukin 12 p35 subunit comprising: 
 a 5′ region of nucleobases, each containing a 2′-MOE modification;    a central region containing deoxynucleotides; and    a 3′ region of nucleobases, each containing a 2′-MOE modification.    
     
     
         6 . The chimeric oligonucleotide of  claim 4  comprising SEQ ID NO: 23, 24 or 44.  
     
     
         7 . A method of inhibiting the expression of Interleukin 12 p35 subunit in cells or tissues comprising contacting said cells or tissues with the compound of  claim 1  so that expression of Interleukin 12 p35 subunit is inhibited.  
     
     
         8 . A method of treating an animal having a disease or condition associated with Interleukin 12 p35 subunit comprising administering to said animal a therapeutically or prophylactically effective amount of the compound of  claim 1  so that expression of Interleukin 12 p35 subunit is inhibited.  
     
     
         9 . The method of  claim 8  wherein the disease or condition is selected from the group consisting of an autoimmune disorder, cancer, a metabolic disorder, or a viral or bacterial infection.  
     
     
         10 . The method of  claim 9  wherein the autoimmune disorder is multiple sclerosis, diabetes or Crohn's disease.  
     
     
         11 . The method of  claim 9  wherein the infection is endotoxemia.  
     
     
         12 . The method of  claim 9  wherein the metabolic disorder is selected from the group consisting of obesity, cardiovascular disease, metabolic syndrome, diabetes, or insulin resistance.  
     
     
         13 . A method for inhibiting the differentiation of an adipocyte cell comprising contacting a preadipocyte cell with an effective amount of a compound of  claim 1 , whereby adipocyte differentiation is inhibited.  
     
     
         14 . A method for inhibiting lipid accumulation in a cell comprising contacting a cell with a compound of  claim 1 , whereby lipid accumulation in the cell is inhibited.