Nucleic acids for inhibiting expression of a target gene comprising phosphorodithioate linkages

A method of preventing or treating a disease, disorder or syndrome, the method comprising administering to a subject a composition comprising a nucleic acid, comprising at least one duplex region that comprises at least a portion of a first strand and at least a portion of a second strand that is at least partially complementary to the first strand, wherein said first strand is at least partially complementary to at least a portion of RNA transcribed from said target gene,

• wherein the nucleic acid comprises phosphorodithioate linkages between the two terminal nucleotides at the 3′ end of the first strand, and
• between the two terminal nucleotides at the 3′ end and the two terminal nucleotides at the 5′ end of the second strand;
• and
• wherein the first strand comprise a linkage other than a phosphorodithioate between the two, three or four terminal nucleotides at the 5′ end.