RNA interference mediated inhibition of winged helix nude (WHN) gene expression using short interfering nucleic acid (siNA)

A double stranded nucleic acid molecule having structure SII comprising a sense strand and an antisense strand:

• wherein the upper strand is the sense strand and the lower strand is the antisense strand of the double stranded nucleic acid molecule;
• said antisense strand comprises sequence complementary to a Winged Helix Nude (WHN) RNA;
• each N is independently a nucleotide;
• each B is a terminal cap moiety that can be present or absent;
• (N) represents non-base paired or overhanging nucleotides which can be unmodified or chemically modified;
• [N] represents nucleotide positions wherein any purine nucleotides when present are ribonucleotides;
• X1 and X2 are independently integers from about 0 to about 4;
• X3 is an integer from about 9 to about 30;
• X4 is an integer from about 11 to about 30, provided that the sum of X4 and X5 is about 16-36;
• X5 is an integer from about 1 to about 6;
• and
• (a) any pyrimidine nucleotides present in the antisense strand are 2′-deoxy-2′-fluoro nucleotides;
• any purine nucleotides present in the antisense strand other than the purines nucleotides in the [N] nucleotide positions, are 2′-O-methyl nucleotides;
• (b) any pyrimidine nucleotides present in the sense strand are ribonucleotides;
• any purine nucleotides present in the sense strand are ribonucleotides;
• and
• (c) any (N) nucleotides are optionally deoxyribonucleotides.

A double stranded nucleic acid molecule having structure Sill comprising a sense strand and an antisense strand:

• wherein the upper strand is the sense strand and the lower strand is the antisense strand of the double stranded nucleic acid molecule;
• said antisense strand comprises sequence complementary to a Winged Helix Nude (WHN) RNA;
• each N is independently a nucleotide;
• each B is a terminal cap moiety that can be present or absent;
• (N) represents non-base paired or overhanging nucleotides which can be unmodified or chemically modified;
• [N] represents nucleotide positions wherein any purine nucleotides when present are ribonucleotides;
• X1 and X2 are independently integers from about 0 to about 4;
• X3 is an integer from about 9 to about 30;
• X4 is an integer from about 11 to about 30, provided that the sum of X4 and X5 is about 16-36;
• X5 is an integer from about 1 to about 6;
• and
• (a) any pyrimidine nucleotides present in the antisense strand are 2′-deoxy-2′-fluoro nucleotides;
• any purine nucleotides present in the antisense strand other than the purines nucleotides in the [N] nucleotide positions, are 2′-O-methyl nucleotides;
• (b) any pyrimidine nucleotides present in the sense strand are 2′-deoxy-2′-fluoro nucleotides;
• any purine nucleotides present in the sense strand are ribonucleotides;
• and
• (c) any (N) nucleotides are optionally deoxyribonucleotides.

A double stranded nucleic acid molecule having structure SIV comprising a sense strand and an antisense strand:

• wherein the upper strand is the sense strand and the lower strand is the antisense strand of the double stranded nucleic acid molecule;
• said antisense strand comprises sequence complementary to a Winged Helix Nude (WHN) RNA;
• each N is independently a nucleotide;
• each B is a terminal cap moiety that can be present or absent;
• (N) represents non-base paired or overhanging nucleotides which can be unmodified or chemically modified;
• [N] represents nucleotide positions wherein any purine nucleotides when present are ribonucleotides;
• X1 and X2 are independently integers from about 0 to about 4;
• X3 is an integer from about 9 to about 30;
• X4 is an integer from about 11 to about 30, provided that the sum of X4 and X5 is 16-36;
• X5 is an integer from about 1 to about 6;
• and
• (a) any pyrimidine nucleotides present in the antisense strand are 2′-deoxy-2′-fluoro nucleotides;
• any purine nucleotides present in the antisense strand other than the purines nucleotides in the [N] nucleotide positions, are 2′-O-methyl nucleotides;
• (b) any pyrimidine nucleotides present in the sense strand are 2′-deoxy-2′-fluoro nucleotides;
• any purine nucleotides present in the sense strand are deoxyribonucleotides;
• and
• (c) any (N) nucleotides are optionally deoxyribonucleotides.

A double stranded nucleic acid molecule having structure SV comprising a sense strand and an antisense strand:

• wherein the upper strand is the sense strand and the lower strand is the antisense strand of the double stranded nucleic acid molecule;
• said antisense strand comprises sequence complementary to a Winged Helix Nude (WHN) RNA;
• each N is independently a nucleotide;
• each B is a terminal cap moiety that can be present or absent;
• (N) represents non-base paired or overhanging nucleotides which can be unmodified or chemically modified;
• [N] represents nucleotide positions wherein any purine nucleotides when present are ribonucleotides;
• X1 and X2 are independently integers from about 0 to about 4;
• X3 is an integer from about 9 to about 30;
• X4 is an integer from about 11 to about 30, provided that the sum of X4 and X5 is about 16-36;
• X5 is an integer from about 1 to about 6;
• and
• (a) any pyrimidine nucleotides present in the antisense strand are nucleotides having a ribo-like, Northern or A-form helix configuration;
• any purine nucleotides present in the antisense strand other than the purines nucleotides in the [N] nucleotide positions, are 2′-O-methyl nucleotides;
• (b) any pyrimidine nucleotides present in the sense strand are nucleotides having a ribo-like, Northern or A-form helix configuration;
• any purine nucleotides present in the sense strand are 2′-O-methyl nucleotides;
• and
• (c) any (N) nucleotides are optionally deoxyribonucleotides.