The present invention is directed to modified siRNA which are significantly impaired in their ability to support cleavage of mRNA when incorporated into a RISC complex. Such modified siRNA may be useful as therapeutic agents, e.g., in the treatment of various cancer forms. More particularly, the modified siRNA comprises a sense strand and an antisense strand, wherein the sense strand contains a modified RNA nucleotide in at least one of positions 8-14, calculated from the 5'-end.