Patent ID: 8252755

Claim:
A duplex oligonucleotide complex comprising: a. a sense strand that is 19 nucleotides in length, wherein nucleotides 1 and 2 and all C nucleotides and all U nucleotides on said sense strand are 2′O-methyl modified; b. an antisense strand that is 21 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 100% complementarity with a target mRNA and one mismatched nucleotide with the sense strand; and iii. the sense strand and the antisense strand form a duplex having a 2 nucleotide overhang at the 3′ end of the antisense strand, said 2 nucleotide overhang comprising phosphorothioate linkages; 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: d. a phosphate group at the 5′ end of the antisense strand; and e. a mismatch between nucleotide 14 on the antisense strand and the opposite nucleotide 6 on the sense strand, wherein all other nucleotides on the sense strand are complementary to nucleotides on the antisense strand; and wherein the duplex oligonucleotide complex is capable of entry into a cell by passive delivery.