Compositions and methods for inhibiting LPA expression

A method for treating a subject having a disease, disorder or condition associated with increased LPA expression, the method comprising administering to the subject a therapeutically effective amount of an RNAi oligonucleotide, the oligonucleotide comprising a sense strand and an antisense strand, wherein the sense strand and the antisense strand form a duplex region, wherein the antisense strand is:

• (SEQ ID NO:
• 793)
• 5′-[MePhosphonate-40-mUs][fAs][fGs][fA][fU][mG]
• [fA][mC][mC][fA][mA][mG][mC][fU][mU][mG][mG][mC]
• [mA][mAs][mGs][mG]-3′, and
• the sense strand is:
• (SEQ ID NO:
• 393)
• 5′-[mUs][mU][mG][mC][mC][mA][mA][fG][fC][fU][fU]
• [mG][mG][mU][mC][mA][mU][mC][mU][mA][mG][mC][mA]
• [mG][mC][mC][mG][ademA-GalNAc][ademA-GalNAc]
• [ademA-GalNAc][mG][mG][mC][mU][mG][mC]-3′,
• wherein:
• mA represents 2′-OMe adenosine;
• mC represents 2′-OMe cytosine;
• mG represents 2′-OMe guanosine;
• mU represents 2′-OMe uridine;
• fA represents 2′-F adenosine;
• fC represents 2′-F cytosine;
• fG represents 2′-F guanosine;
• fU represents 2′-F uridine;
• fAs represents 2′-F adenosine with a 3′-phosphorothioate linkage;
• fGs represents 2′-F guanosine with a 3′-phosphorothioate linkage;
• mAs represents 2′-OMe adenosine with a 3′-phosphorothioate linkage;
• mGs represents 2′-OMe guanosine with a 3′-phosphorothioate linkage;
• mUs represents 2′-OMe uridine with a 3′-phosphorothioate linkage;
• ademA-GalNAc represents 2′-aminodiethoxymethanol-adenine-GalNAc:
• and
• MePhosphonate-40-mUs represents
• thereby treating the subject.