Double-stranded nucleic acid inhibitor molecules with shortened sense strands

A double-stranded nucleic acid inhibitor molecule, comprising:

• a sense strand comprising 15-43 nucleotides and having a first region (R1) and a second region (R2);
• an antisense strand comprising 18-35 nucleotides and a 5′- and 3′-end, wherein the antisense strand has a single stranded overhang of 6-10 nucleotides at the 3′-end and wherein the sense strand and antisense strand are separate strands;
• a first duplex (D1) formed by the first region of the sense strand and the antisense strand, wherein the first duplex has a length of 8-29 base pairs;
• wherein the second region of the sense strand comprises a first subregion (S1), a second subregion (S2) and a single stranded loop that joins the first and second subregions, wherein the first and second subregions form a second duplex (D2);
• and
• wherein the second duplex has a length of 6 base pairs and does not contain a Tm-increasing nucleotide or has a length of 1-5 base pairs and comprises at least one Tm-increasing nucleotide.