Antisense modulation of stearoyl-coa desaturase expression

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of stearoyl-CoA desaturase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding stearoyl-CoA desaturase. Methods of using these compounds for modulation of stearoyl-CoA desaturase expression and for treatment of diseases associated with expression of stearoyl-CoA desaturase are provided.

1 . A compound 8 to 80 nucleobases in length targeted to a nucleic acid molecule encoding human stearoyl-CoA desaturase (SCD1), wherein the compound specifically hybridizes with a nucleic acid molecule encoding human stearoyl-CoA desaturase and inhibits the expression of human stearoyl-CoA desaturase by at least 50%. 
     
     
         2 . The compound of  claim 1 , wherein the compound comprises at least 8 consecutive nucleobases of a nucleobase sequence selected from any of SEQ ID NOs: 83, 84, 85, 87, 88, 89, 90, 91, 93, 94, 95, 97, 98, 100, 101, 102, 103, 105, 107, 108, 109, 110, 111, 113, 114, 115, 117, 118, 119, 120, 124, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 149, 150, 153, 154, 157, 158, 159, 160, 164, 165, 167, 168, 169, 188, 189, 197, 204, 207 or 210. 
     
     
         3 . The compound of  claim 1 , wherein the compound inhibits stearoyl-CoA desaturase by at least 60%, at least 70%, at least 80% or at least 90%. 
     
     
         4 . The compound of  claim 1 , wherein the compound is at least 90%, at least 95% or 100% complementary to the sequence of SEQ ID NO: 3. 
     
     
         5 . The compound of  claim 1 , wherein the compound comprises 8 to 50 nucleobases, 15 to 40 nucleobases, 15 to 35 nucleobases or 15 to 25 nucleobases in length. 
     
     
         6 . The compound of  claim 5 , wherein the compound is 20 nucleobases in length. 
     
     
         7 . The compound of  claim 1 , wherein the compound comprises an antisense oligonucleotide. 
     
     
         8 . The compound according to  claim 7 , wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage. 
     
     
         9 . The compound according to  claim 8 , wherein the modified internucleoside linkage is a phosphorothioate linkage. 
     
     
         10 . The compound according to  claim 7 , wherein the antisense oligonucleotide comprises at least one modified sugar moiety. 
     
     
         11 . The compound according to  claim 10 , wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety. 
     
     
         12 . The compound according to  claim 7 , wherein the antisense oligonucleotide comprises at least one modified nucleobase. 
     
     
         13 . The compound according to  claim 12 , wherein the modified nucleobase is a 5-methylcytosine. 
     
     
         14 . The compound of  claim 7 , wherein the antisense oligonucleotide is a chimeric oligonucleotide. 
     
     
         15 . The compound according to  claim 14 , wherein the chimeric oligonucleotide is 20 nucleotides in length, comprising ten 2′-deoxynucleotides, flanked on each side by five 2′-methoxyethyl nucleotides, wherein the internucleoside linkages are phosphorothioate, and all cytosine residues are 5-methylcytosines.