Double-stranded RNA (dsRNA) directs gene-specific, post-transcriptional sil
encing in many organisms, including vertebrates, and has provided a new too
l for studying gene function. The biochemical mechanisms underlying this ds
RNA interference (RNAi) are unknown. Here we report the development of a ce
ll-free system from syncytial blastoderm Drosophila embryos that recapitula
tes many of the features of RNAi. The interference observed in this reactio
n is sequence specific, is promoted by dsRNA but not single-stranded RNA, f
unctions by specific mRNA degradation, and requires a minimum length of dsR
NA. Furthermore, preincubation of dsRNA potentiates its activity. These res
ults demonstrate that RNAi can be mediated by sequence-specific processes i
n soluble reactions.