RNA sequence-specific mediators of RNA interference

US8552171B2 · kind B2 · utility

Assignees

• University of Massachusetts · US
• Whitehead Institute For Biomedical Research · US
• Massachusetts Institute of Technology · US
• Max-Planck-Gesellschaft zur Föderung der Wissenschaften e.V. · US

Inventors

• Thomas Tuschl · Oettingen, DE
• Phillip D. Zamore · Marlborough, US
• Phillip A. Sharp · Newton, US
• David P. Bartel · Brookline, US

Key dates

• Filing date: Oct 4, 2010
• Grant date: Oct 8, 2013
• Expiry date: Oct 4, 2030

Classification

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

Abstract

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.