RNA interference mediating small RNA molecules

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RNA interference mediating small RNA molecules
United States Patent 7,078,196
Tuschl , et al.
July 18, 2006
Inventors: Tuschl; Thomas (New York, NY); Elbashir; Sayda Mahgoub (Cambridge, MA); Lendeckel; Winfried (Hohengendern, DE)
Assignee: Max-Planck-Gesellschaft zur Foerderung der Wissenschaften, e.V. (Munich, DE)
Appl. No.: 832248
Filed: April 27, 2004
Abstract
Double-stranded RNA (dsRNA) induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). Using a Drosophila in vitro system, we demonstrate that 19 23 nt short RNA fragments are the sequence-specific mediators of RNAi. The short interfering RNAs (siRNAs) are generated by an RNase III-like processing reaction from long dsRNA. Chemically synthesized siRNA duplexes with overhanging 3' ends mediate efficient target RNA cleavage in the lysate, and the cleavage site is located near the center of the region spanned by the guiding siRNA. Furthermore, we provide evidence that the direction of dsRNA processing determines whether sense or antisense target RNA can be cleaved by the produced siRNP complex.