Modified polynucleotides for use in rna interference

A synthetic siRNA for interacting with a target mRNA of a target gene, the siRNA comprising:

• a sense strand comprising:
• a sense region;
• a first nucleotide of the sense strand closest to the 5′ end of the sense strand having a 2′-O-alkyl modification;
• and
• a second nucleotide of the sense strand next closest to the 5′ end of the sense strand having a 2′-O-alkyl modification;
• and
• an antisense strand comprising an antisense region which is at least substantially complementary with the mRNA of the target gene and the sense region;
• and

A synthetic siRNA for interacting with a target mRNA of a target gene, the siRNA comprising:

• a sense strand comprising:
• a sense region;
• a first nucleotide of the sense strand closest to the 5′ end of the sense strand having a 2′-O-alkyl modification and being devoid of a phosphate at its 5′ end;
• and
• a second nucleotide of the sense strand next closest to the 5′ end of the sense strand having a 2′-O-alkyl modification;
• and
• an antisense strand comprising:
• an antisense region which is at least substantially complementary with the mRNA of the target gene and the sense region;
• a first nucleotide of the antisense strand closest to the 5′ end of the antisense strand having a 2′-O-alkyl modification and a phosphate at its 5′ end;
• and
• a second nucleotide of the antisense strand next closest to the 5′ end of the antisense strand having a 2′-O-alkyl modification.

A synthetic siRNA for interacting with a target mRNA of a target gene, the siRNA comprising:

• a sense strand comprising:
• a sense region;
• a first nucleotide of the sense strand closest to the 5′ end of the sense strand having a 2′-O-alkyl modification and being devoid of a phosphate at its 5′ end;
• a second nucleotide of the sense strand next closest to the 5′ end of the sense strand having a 2′-O-alkyl modification;
• and
• at least one pyrimidine nucleotide of the sense strand having a 2′-O-alkyl modification, wherein the pyrimidine nucleotide is a nucleotide other than said first or second nucleotides of the sense strand;
• and
• an antisense strand comprising:
• an antisense region which is at least substantially complementary with the mRNA of the target gene and the sense region;
• a first nucleotide of the antisense strand closest to the 5′ end of the antisense strand having a 2′-O-alkyl modification and a phosphate at its 5′ end;
• a second nucleotide of the antisense strand next closest to the 5′ end of the antisense strand having a 2′-O-alkyl modification;
• and
• at least one pyrimidine nucleotide other than the first and second nucleotides of the antisense strand having a 2′-halogen modification.