RNA interference mediating small RNA molecules

US7078196B2 · kind B2 · utility

Assignee

• Max-Planck-Gesellschaft zur Föderung der Wissenschaften e.V. · US

Inventors

• Thomas Tuschl · Oettingen, DE
• Sayda M. Elbashir · Cambridge, US
• Winfried Lendeckel · Hohengandern, DE

Key dates

• Filing date: Apr 27, 2004
• Grant date: Jul 18, 2006
• Expiry date: Apr 27, 2024

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2330/30
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

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.