Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells

RNA interference (RNAi) is the process of sequence-specific, post-transcrip tional gene silencing in animals and plants, initiated by double-stranded R NA (dsRNA) that is homologous in sequence to the silenced gene(1-4). The me diators of sequence-specific messenger RNA degradation are 21- and 22-nucle otide small interfering RNAs (siRNAs) generated by ribonuclease III cleavag e from longer dsRNAs(5-9). Here we show that 21-nucleotide siRNA duplexes s pecifically suppress expression of endogenous and heterologous genes in dif ferent mammalian cell lines, including human embryonic kidney (293) and HeL a cells. Therefore, 21-nucleotide siRNA duplexes provide a new tool for stu dying gene function in mammalian cells and may eventually be used as gene-s pecific therapeutics.