The present invention relates to a Drosophila in vitro system which was
used to demonstrate that dsRNA is processed to RNA segments 21-23
nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments
are purified and added back to Drosophila extracts, they mediate RNA
interference in the absence of long dsRNA. Thus, these 21-23 nt fragments
are the sequence-specific mediators of RNA degradation. A molecular
signal, which may be their specific length, must be present in these
21-23 nt fragments to recruit cellular factors involved in RNAi. This
present invention encompasses these 21-23 nt fragments and their use for
specifically inactivating gene function. The use of these fragments (or
chemically synthesized oligonucleotides of the same or similar nature)
enables the targeting of specific mRNAs for degradation in mammalian
cells, where the use of long dsRNAs to elicit RNAi is usually not
practical, presumably because of the deleterious effects of the
interferon response. This specific targeting of a particular gene
function is useful in functional genomic and therapeutic applications.