Isis Pharmaceuticals, Inc.

Nitto Denko Avecia, Inc.

Tadeusz Krzysztof Wyrzykiewicz

Eric E Swayze

Michael T Migawa

Phillip Dan Cook

Thazha P Prakash

Balkrishen Bhat

Stanley T Crooke

Walter F Lima

Hongjiang Wu

Hagen Cramer

Huihe Zhu

Kevin James Finn

Joshua Nichols

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

The present invention relates to bicyclic nucleosides and oligomeric compounds comprising at least one such nucleoside. These oligomeric compounds typically have enhanced binding affinity and nuclease resistance properties compared to unmodified oligomeric compounds. The oligomeric compounds are useful, for example, for investigative and therapeutic purposes.

Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini

A process for manufacturing an oligonucleotide which comprises removing &#x3b2;-eliminating phosphorus-protecting groups, in particular &#x3b2;-cyanoethyl protective groups from a protected oligonucleotide, wherein said removing comprises contacting the protected oligonucleotide with an amine solution in a solvent which preferably does not consist of pyridine, wherein the conjugate acid of the amine has preferably a pKa of greater than 11.5, and wherein the concentration of the amine in the solution is less than 0.5 mole/liters.

Process for the manufacture of oligonucleotides

The present invention is directed to &#x3b1;-modified nucleoside triphosphates and methods for their preparation. The present invention also provides for methods of inhibiting RNA and viral replication in cells, as well as methods for treating viral infections.

&#x3b1;-modified nucleoside triphosphates

This invention presents novel methods for desulfurizing and sequencing phosphorothioate oligonucleotides. These methods allow easy access to the analysis of phosphorothioate oligonucleotides because these methods may be performed as a final step in oligonucleotide synthesis. The methods of the invention will permit rapid characterization of oligonucleotides and may be easily adapted to characterizing pharmaceutical formulations.

Methods for characterizing phosphorothioate oligonucleotides

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Wyoming, OH, United States of America

Tadeusz Krzysztof Wyrzykiewicz