Extrahepatic delivery

A double-stranded iRNA agent comprising:

• an antisense strand which is complementary to a target mRNA;
• a sense strand which is complementary to said antisense strand;
• and
• one lipophilic moiety directly bonded to a 2′-O of a sugar moiety at an internal position of the sense strand, wherein:
• the sense and antisense strands are each independently 19 to 25 nucleotides in length and form a double-stranded region 19-21 nucleotide pairs in length, having a blunt end at the 5′-end of the antisense strand;
• the lipophilic moiety is a linear C16 alkyl chain;
• the internal position is a position on the sense strand excluding the three terminal positions from each of the 5′-end and 3′-end of the sense strand and excluding positions 11 to 13, counting from the 3′-end of the sense strand;
• and
• the double-stranded iRNA agent does not comprise a N-acetylgalactosamine (GalNAc) conjugate.