Chemically modified oligonucleotides for use in modulation micro RNA and uses thereof

A method of reducing plasma cholesterol levels in a mammal, the method comprising administering an antagomir to the mammal, wherein the antagomir is 15 to 25 nucleotides in length and has no more than two mismatches to the sequence ofmiR-122 (SEQ ID NO:

• 1), further wherein said antagomir comprises a non-nucleotide moiety at the 3′ -end, a 2′ -modification at each nucleotide, a phosphorothioate at the first and second internucleotide linkages at the 5′ end of the nucleotide sequence, a phosphorothioate at each of the first three internucleotide linkages at the 3′ end of the nucleotide sequence, and a phosphorothioate linkage between the 3′ terminal nucleotide and the non-nucleotide moiety, and wherein the remaining internucleotide linkages are phosphodiester.