Whitehead Institute for Biomedical Research

Massachusetts Institute of Technology

University of Massachusetts

Max-planck-gesellschaft Zur F&#xf6;rderung Der Wissenschaften E. V.

Regulus Therapeutics Inc.

David P Bartel

Thomas Tuschl

Phillip D Zamore

Phillip A Sharp

Balkrishen Bhat

Neil W Gibson

Diedre MacKenna

Brandee Wagner

Donald Scott Baskerville

Harvey F Lodish

Chang-Zheng Chen

Hazel Sive

Grace Chen

Michael Axtell

Charles Everett Merryman

Philip D Zamore

Methods and compositions for increasing RNAi efficiency through single nucleotide mismatches.

Increasing RNAi efficiency through single nucleotide mismatches

The present invention relates to ain 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 toextracts, 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.

RNA sequence-specific mediators of RNA interference

Described herein are compounds comprising modified oligonucleotides that are complementary to miR-103 and/or miR-107 and methods of treating diseases and disorders using the compounds.

Targeting microRNAs for metabolic disorders

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.

The invention relates to microRNAs, methods of producing microRNAs and methods for using microRNAs.

Methods and products for expression of micro RNAs

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Brookline, MA, United States of America

David P Bartel