Patent ID: 8501706

Claim:
A method for inhibiting expression of a target gene in a cell, the method comprising delivering to said cell a duplex oligonucleotide complex comprising: a. a sense strand that is nineteen nucleotides in length, wherein nucleotides 1 and 2 and all C and all U nucleotides on said sense strand are 2′O-methyl modified and the sense strand has a 3′ end; b. an antisense strand that is twenty-one nucleotides in length, wherein i. all C nucleotides and all U nucleotides on said antisense strand are 2′F modified; ii. the antisense strand has a 5′ end and a 3′ end and one mismatched nucleotide with the sense strand at position 14 within the antisense strand and the opposite nucleotide 6 on the sense strand, wherein all other nucleotides within the sense strand are complementary to nucleotides on the antisense strand; and iii. the sense strand and the antisense strand form a duplex having a two nucleotide overhang at the 3′end of the antisense strand; c. a cholesterol molecule attached to the 3′ end of the sense strand via a C5 linker molecule, wherein the cholesterol-linker-sense strand has the structure: and d. a phosphate group at the 5′ end of the antisense strand, wherein following said delivering the expression of a target protein is decreased.