Modulation of apolipoprotein ciii (apociii) expression

Abstract

Provided herein are methods, compounds, and compositions for reducing expression of ApoCIII mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for increasing HDL levels and/or improving the ratio of TG to HDL and reducing plasma lipids and plasma glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease or metabolic disorder, or a symptom thereof.

1 - 5 . (canceled) 
     
     
         6 . A method of preventing, delaying or ameliorating pancreatitis in an animal with, or at risk of pancreatitis, and wherein the animal has triglyceride levels of ≥1000 mg/dL, comprising
 administering a modified oligonucleotide consisting of the sequence of SEQ ID NO: 3 to the animal, 
 
       wherein the pancreatitis is prevented, delayed or ameliorated. 
     
     
         7 - 15 . (canceled) 
     
     
         16 . The method of  claim 6 , wherein the animal has a triglyceride level of ≥1100 mg/dL, ≥1200 mg/dL, ≥1300 mg/dL, ≥1400 mg/dL, ≥1500 mg/dL, ≥1600 mg/dL, ≥1700 mg/dL, ≥1800 mg/dL, ≥1900 mg/dL, ≥2000 mg/dL, ≥2100 mg/dL, ≥2200 mg/dL, ≥2300 mg/dL, ≥2400 mg/dL or ≥2500 mg/dL. 
     
     
         17 - 30 . (canceled) 
     
     
         31 . The method of  claim 6 , wherein at least one internucleoside linkage of the modified oligonucleotide is a modified internucleoside linkage. 
     
     
         32 . The method of  claim 31 , wherein each modified internucleoside linkage of the modified oligonucleotide is a phosphorothioate internucleoside linkage. 
     
     
         33 . The method of  claim 6 , wherein at least one nucleoside of the modified oligonucleotide comprises a modified sugar. 
     
     
         34 . The method of  claim 33 , wherein at least one modified sugar is a bicyclic sugar. 
     
     
         35 . The method of  claim 33 , wherein at least one modified sugar comprises a 2′-O-methoxyethyl. 
     
     
         36 . The method of  claim 6 , wherein at least one nucleoside of the modified oligonucleotide comprises a modified nucleobase. 
     
     
         37 . The method of  claim 36 , wherein the modified nucleobase is a 5-methylcytosine. 
     
     
         38 . (canceled) 
     
     
         39 . (canceled) 
     
     
         40 . The method of  claim 6 , wherein the modified oligonucleotide comprises:
 (a) a gap segment consisting of 10 linked deoxynucleosides;   (b) a 5′ wing segment consisting of 5 linked nucleosides;   (c) a 3′ wing segment consisting 5 linked nucleosides;   
       wherein the gap segment is positioned immediately adjacent to and between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a 2′-O-methoxyethyl sugar, wherein each cytosine is a 5-methylcytosine, and wherein each internucleoside linkage is a phosphorothioate linkage. 
     
     
         41 - 76 . (canceled) 
     
     
         77 . The method of  claim 6 , wherein postprandial triglycerides are reduced. 
     
     
         78 . The method of  claim 6 , wherein the modified oligonucleotide is parenterally administered. 
     
     
         79 . The method of  claim 78 , wherein the parenteral administration is subcutaneous administration. 
     
     
         80 - 85 . (canceled) 
     
     
         86 . The method of  claim 6 , wherein the animal has a genetic defect leading to hypertriglyceridemia. 
     
     
         87 . The method of  claim 6 , wherein the animal is human.