Modified double stranded oligonucleotide

A dsRNA agent comprising:

• a sense strand having a length of 17-35 nucleotides;
• an antisense strand having a length of 17-35 nucleotides;
• at least two phosphorothioate internucleotide linkages between the first five nucleotides of the antisense strand, counting from the 5′ end of the antisense strand;
• and
• only three, four, five or six 2′-deoxy modifications on the antisense strand;
• wherein:
• at least two 2′-deoxy modifications are in a central region of the sense strand, wherein the central region of the sense strand is positions 7, 8, 9, 10, 11, 12, and 13 counting from the 5′-end of the sense strand;
• three of the 2′-deoxy modifications of the antisense strand are at positions 2, 12, and 14, counting from the 5′-end of the antisense strand;
• the sense strand and the antisense strand form a duplex region containing between 17 to 25 base pairs;
• the dsRNA agent comprises a ligand;
• the sense strand does not comprise a glycol nucleic acid (GNA);
• and
• the 2′-deoxy modifications are not 2′-deoxy-2′-fluoro (2′-F) nucleoside.