The present invention refers to a double-stranded siRNA molecule comprising a sense Strand and an antisense Strand which is essentially complementary to the sense Strand, each of the sense and the antisense Strands comprising at least 17 nucleotides (nt), the siRNA further comprising at least one overhang at the 5' and/or 3' end, wherein the overhang residue or overhang residues are chemically modified and selected independently from each other from the group consisting of: (a) 2'-deoxy modified nucleotides; (b) 2'-methoxy modified nucleotides; (c) two nucleosides linked by a 3' to 5' or 2' to 5' formacetal linkage; (d) nucleotides modified at the 2'-position by a -0-CH2-O-(CH2)2-OH group; and (e) nucleotides comprising in the 3'-position a -CH2-O-(CH2)7-CH3 group.