Compositions and their uses directed to aceytl-coa carboxylases

Abstract

Disclosed herein are compounds, compositions and methods for modulating the expression of ACC1 or ACC2 or both in a cell, tissue or animal. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders.

1 - 28 . (canceled) 
     
     
         29 . A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides having a nucleobase sequence at least 85% complementary to:
 a nucleic acid molecule encoding human ACC1;   a nucleic acid molecule encoding human ACC2; or   a nucleic acid molecule encoding human ACC1 and a nucleic acid molecule encoding ACC2;   
       as measured over the entirety of the nucleobase sequence of the modified oligonucleotide. 
     
     
         30 . The compound of  claim 29  wherein the modified oligonucleotide comprises at least one chemical modification selected from a modified internucleoside linkage, a modified nucleobase, and a modified sugar. 
     
     
         31 . The compound of  claim 29 , wherein said modified oligonucleotide is a chimeric oligonucleotide. 
     
     
         32 . The antisense oligonucleotide compound of  claim 30 , wherein the modified oligonucleotide comprises at least one modified internucleoside linkage. 
     
     
         33 . The compound of  claim 48 , wherein the modified nucleobase is a 5 methylcytosine. 
     
     
         34 - 42 . (canceled) 
     
     
         43 . The compound of  claim 32 , wherein the modified internucleoside linkage is a phosphorothioate linkage. 
     
     
         44 . The compound of  claim 30 , wherein the modified oligonucleotide comprises a modified sugar moiety. 
     
     
         45 . The compound of  claim 44 , wherein the modified sugar comprises a 2′-O-(2-methoxyethyl) moiety. 
     
     
         46 . The compound of  claim 44 , wherein the modified sugar comprises a bicyclic modified sugar moiety. 
     
     
         47 . The compound of  claim 46 , wherein the bicyclic modified sugar moiety comprises a 4′-(CH2) 2 -O-2′ bridge. 
     
     
         48 . The compound of  claim 30 , wherein the modified oligonucleotide comprises a modified nucleobase. 
     
     
         49 . The compound of  claim 31 , wherein the chimeric oligonucleotide comprises a first region comprising 2-deoxynucleotides and a second and third region flanking said first region, comprising at least one modified sugar moiety. 
     
     
         50 . The compound of  claim 29 , wherein the modified oligonucleotide is at least 90% complementary to a nucleic acid molecule encoding human ACC1 as measured over the entirety of the nucleobase sequence of the modified oligonucleotide. 
     
     
         51 . The compound of  claim 29 , wherein the modified oligonucleotide is at least 95% complementary to a nucleic acid molecule encoding human ACC1 as measured over the entirety of the nucleobase sequence of the modified oligonucleotide. 
     
     
         52 . The compound of  claim 29 , wherein the modified oligonucleotide is 100% complementary to a nucleic acid molecule encoding human ACC1 as measured over the entirety of the nucleobase sequence of the modified oligonucleotide. 
     
     
         53 . The compound of  claim 29 , wherein the modified oligonucleotide is at least 90% complementary to a nucleic acid molecule encoding human ACC2 as measured over the entirety of the nucleobase sequence of the modified oligonucleotide. 
     
     
         54 . The compound of  claim 29 , wherein the modified oligonucleotide is at least 95% complementary to a nucleic acid molecule encoding human ACC2 as measured over the entirety of the nucleobase sequence of the modified oligonucleotide. 
     
     
         55 . The compound of  claim 29 , wherein the modified oligonucleotide is 100% complementary to a nucleic acid molecule encoding human ACC2 as measured over the entirety of the nucleobase sequence of the modified oligonucleotide. 
     
     
         56 . The compound of  claim 29 , wherein the modified oligonucleotide is at least 90% complementary to a nucleic acid molecule encoding human ACC1 and at least 90% complementary to a nucleic acid molecule encoding human ACC2 measured over the entirety of the nucleobase sequence of the modified oligonucleotide. 
     
     
         57 . The compound of  claim 56 , wherein the modified oligonucleotide is at least 95% complementary to a nucleic acid molecule encoding human ACC1 and at least 95% complementary to a nucleic acid molecule encoding human ACC2 as measured over the entirety of the nucleobase sequence of the modified oligonucleotide. 
     
     
         58 . The compound of  claim 57 , wherein the modified oligonucleotide is 100% complementary to a nucleic acid molecule encoding human ACC1 and 100% complementary to a nucleic acid molecule encoding human ACC2 as measured over the entirety of the nucleobase sequence of the modified oligonucleotide. 
     
     
         59 . The compound of  claim 29 , wherein the modified oligonucleotide is 100% complementary to a nucleic acid molecule encoding human ACC1 and at least 85% complementary to a nucleic acid molecule encoding human ACC2 as measured over the entirety of the nucleobase sequence of the modified oligonucleotide. 
     
     
         60 . The compound of  claim 29 , wherein the modified oligonucleotide is at least 85% complementary to a nucleic acid molecule encoding human ACC1 and 100% complementary to a nucleic acid molecule encoding human ACC2 as measured over the entirety of the nucleobase sequence of the modified oligonucleotide. 
     
     
         61 . The compound of  claim 49 , wherein the modified sugar moiety is a 2′-O-(2-methoxyethyl) moiety.