MODULATION OF TRANSTHYRETIN EXPRESSION
Provided herein are methods, compounds, and compositions for reducing expression of transthyretin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate transthyretin amyloidosis, or a symptom thereof.
1 - 40 . (canceled)
41 . A compound consisting of a conjugate group and a sodium salt of a single-stranded modified oligonucleotide consisting of 20 linked nucleosides having a nucleobase sequence consisting of SEQ ID NO: 80, wherein the modified oligonucleotide comprises:
a gap segment consisting of ten linked deoxynucleosides;
a 5′ wing segment consisting of five linked nucleosides; and
a 3′ wing segment consisting of five linked nucleosides;
wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment, wherein each nucleoside of each wing segment comprises a 2′-O-methoxyethyl sugar, wherein each internucleoside linkage is a phosphorothioate linkage, and wherein each cytosine of the modified oligonucleotide is a 5-methylcytosine.
42 . A composition comprising the compound of claim 41 .
43 . A method of treating transthyretin amyloidosis in an individual comprising administering to the individual the compound of claim 41 .
44 . The method of claim 43 , wherein the transthyretin amyloidosis is familial amyloid polyneuropathy (FAP).
45 . The method of claim 43 , wherein the transthyretin amyloidosis is familial amyloid cardiopathy (FAC).
46 . A method of treating transthyretin amyloidosis in an individual comprising administering to the individual the composition of claim 42 .
47 . The method of claim 46 , wherein the transthyretin amyloidosis is familial amyloid polyneuropathy (FAP).
48 . The method of claim 46 , wherein the transthyretin amyloidosis is familial amyloid cardiopathy (FAC).