RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)

A chemically modified double-stranded short interfering nucleic acid molecule that mediates RNA interference (RNAi) and comprising a sense strand and an antisense strand that are not connected via a linker molecule, wherein:

• a) each strand of said nucleic acid molecule is independently 18 to 24 nucleotides in length;
• b) a nucleotide sequence of the antisense strand of said nucleic acid molecule is complementary to a mammalian target RNA sequence;
• c) the short interfering nucleic acid molecule has between 17 and 23 base pairs;
• d) the sense strand comprises 10 or more 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, or universal base modified nucleotides, and a plurality of pyrimidine nucleotides present in the sense strand are 2′-deoxy-2′-fluoro pyrimidine nucleotides and a plurality of purine nucleotides present in the sense strand are 2′-deoxy purine nucleotides;
• and
• e) the antisense strand comprises 10 or more 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, or universal base modified nucleotides, and a plurality of pyrimidine nucleotides present in the antisense strand are 2′-deoxy-2′-fluoro pyrimidine nucleotides and a plurality of purine nucleotides present in the antisense strand are 2′-O-methyl purine nucleotides.