Enhancement of RNAi activity by improved siRNA duplexes.

RNA interference (RNAi) is a powerful tool for suppressing the expression of a gene of interest, in which 21-25 nucleotide short interfering RNA (siRNA) duplexes homologous to the silenced gene function as sequence-specific RNAi mediators. The present study shows that newly designed siRNA duplexes, 'fork-siRNA duplexes', whose sense-stranded siRNA elements carry one to four nucleotide mismatches at the 3'-ends against the antisense-stranded siRNA elements, can enhance RNAi activity over conventional siRNA duplexes in cultured mammalian cells.