Synthesis and properties of modified siRNA having amide-linked oligoribonucleosides at their 3' overhang regions.

siRNAs against luciferase gene were modified with amide-linked oligoribonucleosides (amide-linked RNA) at their 3'-overhang regions. The modified siRNAs were more stable than the unmodified siRNA against degradation by nuclease S1, which indicates that the modified overhang regions increase the nuclease resistance of the siRNAs. Tm values of the modified siRNAs increased compared with that of the unmodified siRNA. This result suggests that the modified overhang regions stabilize the duplex structure of siRNAs. The modified siRNAs reduced the target gene expression in a similar manner as the unmodified siRNA in living cells. This result indicates that the overhang modifications are tolerated for the inhibition of target gene expression.