COMPOSITIONS AND METHODS FOR MODULATING HBV EXPRESSION
Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine.
1 - 25 . (canceled)
26 . A compound comprising a modified oligonucleotide and a conjugate group, wherein the modified oligonucleotide consists of 16 linked nucleosides having a nucleobase sequence consisting of the nucleobase sequence of SEQ ID NO: 10, and wherein the conjugate group comprises:
27 . The compound of claim 26 , wherein the modified oligonucleotide comprises at least one modified sugar.
28 . The compound of claim 27 , wherein at least one modified sugar is a bicyclic sugar.
29 . The compound of claim 27 , wherein at least one modified sugar comprises a 2′-O-methoxyethyl, a constrained ethyl, or a 4′-(CH 2 ) n —O-2′ bridge, wherein n is 1 or 2.
30 . The compound of claim 27 , wherein at least one modified sugar is 2′-O-methoxyethyl.
31 . The compound of claim 26 , wherein at least one nucleoside comprises a modified nucleobase.
32 . The compound of claim 31 , wherein the modified nucleobase is a 5-methylcytosine.
33 . The compound of claim 26 , wherein the conjugate group is linked to the modified oligonucleotide at the 5′ end of the modified oligonucleotide.
34 . The compound of claim 26 , wherein the conjugate group is linked to the modified oligonucleotide at the 3′ end of the modified oligonucleotide.
35 . The compound of claim 26 , wherein each internucleoside linkage of the modified oligonucleotide is selected from a phosphodiester internucleoside linkage and a phosphorothioate internucleoside linkage.
36 . The compound of claim 35 , wherein the modified oligonucleotide comprises at least 5 phosphodiester internucleoside linkages.
37 . The compound of claim 35 , wherein the modified oligonucleotide comprises at least two phosphorothioate internucleoside linkages.
38 . The compound of claim 26 , wherein the modified oligonucleotide is single-stranded.
39 . The compound of claim 26 , wherein the modified oligonucleotide is double stranded.
40 . The compound of claim 26 , wherein the modified oligonucleotide comprises:
a gap segment consisting of linked deoxynucleosides;
a 5′ wing segment consisting of linked nucleosides;
a 3′ wing segment consisting of linked nucleosides;
wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar.
41 . The compound of claim 40 , wherein each internucleoside linkage of the modified oligonucleotide is selected from a phosphodiester internucleoside linkage and a phosphorothioate internucleoside linkage.
42 . The compound of claim 41 , wherein each internucleoside linkage in the gap segment of the modified oligonucleotide is a phosphorothioate linkage.
43 . The compound of claim 42 , wherein the modified oligonucleotide further comprises at least one phosphorothioate internucleoside linkage in each wing segment.
44 . The compound of claim 43 , wherein the modified sugar is a bicyclic sugar.
45 . The compound of claim 43 , wherein the modified sugar comprises a 2′-O-methoxyethyl, a constrained ethyl, or a 4′-(CH 2 ) n —O-2′ bridge, wherein n is 1 or 2.
46 . The compound of claim 43 , wherein the modified sugar is 2′-O-methoxyethyl.
47 . The compound of claim 43 , wherein the modified sugar of each wing segment comprises at least one 2′-O-methoxyethyl and at least one constrained ethyl.
48 . The compound of claim 47 , wherein at least one nucleoside comprises a modified nucleobase.
49 . The compound of claim 48 , wherein the modified nucleobase is a 5-methylcytosine.
50 . The compound of claim 49 , wherein the conjugate group is linked to the modified oligonucleotide at the 5′ end of the modified oligonucleotide.
51 . The compound of claim 26 , wherein the modified oligonucleotide comprises:
a gap segment consisting of 10 linked deoxynucleosides;
a 5′ wing segment consisting of 2 linked nucleosides; and
a 3′ wing segment consisting of 4 linked nucleosides;
wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment; wherein the 2 linked nucleosides of the 5′ wing segment comprise a 2′-O-methoxyethyl sugar and a constrained ethyl sugar in the 5′ to 3′ direction; wherein the 4 linked nucleosides of the 3′ wing segment comprise a constrained ethyl sugar, a 2′-O-methoxyethyl sugar, a constrained ethyl sugar, and a 2′-O-methoxyethyl sugar in the 5′ to 3′ direction; and wherein each cytosine residue is a 5-methylcytosine.