Chirally-enriched double-stranded RNA agents

A chirally-modified double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene, said chirally-modified dsRNA agent comprising a sense strand and an antisense strand, each strand having 14 to 40 nucleotides,

• wherein:
• the sense strand comprises one or more terminal, chirally-modified internucleotide linkages at the 5′ end;
• the antisense strand comprises one or more terminal, chirally-modified internucleotide linkages at the 5′ end and one or more terminal, chirally-modified internucleotide linkages at the 3′ end;
• each terminal, chirally-modified internucleotide linkage is a phosphorothioate linkage;
• a terminal, chiral modification occurs at the first internucleotide linkage at the 3′ end of the antisense strand, and the linkage phosphorus atom is in Sp configuration;
• and
• a terminal, chiral modification occurs at the first internucleotide linkage at the 5′ end of the antisense strand, and the linkage phosphorus atom is in Rp configuration.