Isis Pharmaceuticals, Inc.

Ionis Pharmaceuticals, Inc.

Lonis Pharmaceuticals, Inc.

Alaylam Pharmacueuticals, Inc.

Walter F Lima

Stanley T Crooke

Eric E Swayze

Thazha P Prakash

Hongjiang Wu

Thomas W Bruice

Garth A Kinberger

Balkrishen Bhat

Chikateru Nozaki

Timothy A Vickers

Kevin P Anderson

Ronnie C Hanecak

Fukusaburo Hamada

Hiroshi Nakatake

Tsukasa Nishihara

Tatsuo Eto

Kazuya Hoshiko

Shinichi Furukawa

Muthiah Manoharan

Susan M Freier

Kallanthottathil G Rajeev

Brett P Monia

David J Ecker

Michael T Migawa

Shoji Furusako

Ivan Zlatev

Tadeusz Krzysztof Wyrzykiewicz

Muthiah Monoharan

Joshua Nichols

Shoji Furasako

Heather Murray

Oligonucleotides, chemically-modified oligonucleotides, and oligonucleotide-conjugate complexes for use in research, diagnostics, and/or therapeutics are described herein. In some embodiments, oligonucleotides comprising a stabilized phosphate moiety covalently attached to the 5'-terminal nucleoside are provided.

Oligomer-conjugate complexes and their use

The present invention provides oligomeric compounds and uses thereof. In certain embodiments, such oligomeric compounds are useful as antisense compounds. Certain such antisense compounds are useful as RNase H antisense compounds or as RNAi compounds.

Oligomeric compounds and methods

The present invention provides compounds of formula (1). Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene. 

5'-end derivatives

The present invention provides compositions and methods for the optimization of cleavage of RNA species by RNase H. In some embodiments, the invention provides oligonucleotides that possess two or more regions of differing conformation, and at least one transitional nucleobase positioned between the regions that is capable of modulating transfer of the helical conformation characteristic of the region bound to the 3'hydroxy thereof, to the region bound to the 5&#x2032; hydroxyl thereof.

Compositions and methods for optimizing cleavage of RNA by RNase H

Provided herein are methods for determining potency of RNAi agents. Such methods include, but are not limited to, cell-based and cell-free assays that measure binding of an RNAi agent with Ago2 or that measure Ago2 activity in the presence of such RNAi agents. Also provided are assays that determine potency of RNAi agents by assessing their ability to compete with other RNAi agents, including control RNAi agents, for binding and/or activation of Ago2.

Methods of determining potency of chemically-synthesized oligonucleotides

A human RNase H polypeptide and methods of use are provided.

Human RNase H1 mutants

The present invention provides oligonucleotides that can serve as substrates for human Type 2 RNase H. The present invention is also directed to methods of using these oligonucleotides in enhancing antisense oligonucleotide therapies.

Human Rnase H1 and oligonucleotide compositions thereof

Antisense oligonucleotides are provided which are complementary to and hybridizable with at least a portion of HCV RNA and which are capable of inhibiting the function of the HCV RNA. These oligonucleotides can be administered to inhibit the activity of Hepatitis C virus in vivo or in vitro. These compounds can be used either prophylactically or therapeutically to reduce the severity of diseases associated with Hepatitis C virus, and for diagnosis and detection of HCV and HCV-associated diseases. Methods of using these compounds are also disclosed.

Compositions and methods for treatment of Hepatitis C virus-associated diseases

The present invention provides polynucleotides and polypeptides encoded thereby of human Type 2 RNase H. Methods of using these polynucleotides and polypeptides in enhancing antisense oligonucleotide therapies are also provided.

Human RNase H and compositions and uses thereof

Oligonucleotides which selectively bind to target biomolecules are determined by in vitro assay of a pool of random oligonucleotides for activity against the biomolecules, followed by recovery and characterization of selected oligonucleotides. Oligonucleotides so determined may be utilized for therapeutic, diagnostic and research reagent purposes.

Determination of oligonucleotides for therapeutics, diagnostics and

Human type 2 RNase H

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San Diego, CA, United States of America

Walter F Lima