Isis Pharmaceuticals, Inc.

Ionis Pharmaceuticals, Inc.

Regulus Therapeutics Inc.

Timothy A Vickers

David J Ecker

C Frank Bennett

Susan M Freier

Thomas W Bruice

Jacqueline R Wyatt

Kevin P Anderson

Ronnie C Hanecak

Richard Holmes Griffey

Stanley T Crooke

Brenda F Baker

Vickie L Brown-Driver

Eric E Swayze

Balkrishen Bhat

Nicholas M Dean

Eric G Marcusson

Ravi Jain

James G Karras

Walter F Lima

Christine Esau

Peter W Davis

Erich Koller

Bridget Lollo

Ming-Yi Chiang

Eigen Peralta

Phillip Dan Cook

Lex M Cowsert

Kenneth W Dobie

Yogesh S Sanghvi

John McNeil

Christopher K Mirabelli

Ranjan Perera

Alexander H Borchers

Henri M Sasmor

Jean Louis Imbach

Cara Ohashi

Debra L Robertson

Douglas G Brooks

Disclosed herein are compounds, compositions and methods for modulating the expression of LMNA in a cell, tissue or animal. Also provided are methods of target validation. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. Further provided are methods of identifying cis splicing regulatory elements of a selected mRNA using the disclosed compounds.

Compositions and methods for modulation of LMNA expression

Methods are provided for the identification of compounds that selectively modulate epigenetic changes in gene expression. Compounds, compositions, kits or assays devices, and methods are provided for modulating the expression, endogenous levels or the function of small non-coding RNAs cognate to or transcribed by heterochromatic regions subject to epigenetic regulation (i.e., promoters, enhancers, centromeres, telomeres, origins of DNA replication, imprinted loci, or loci marked by dosage-compensation), and for modulating the formation or function of heterochromatin in cells, tissues or animals.

Regulation of epigenetic control of gene expression

Compounds, compositions and methods are provided for modulating the expression and function of small non-coding RNAs. The compositions comprise oligomeric compounds, targeted to small non-coding RNAs. Methods of using these compounds for modulation of small non-coding RNAs as well as downstream targets of these RNAs and for diagnosis and treatment of disease associated with small non-coding RNAs are also provided.

Method of inhibiting miR-33 using a modified oligonucleotide

Antisense compounds, compositions and methods are provided for modulating the expression of MyD88. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding MyD88. Methods of using these compounds for modulation of MyD88 expression and for treatment of diseases associated with expression of MyD88 are provided.

Modification of MYD88 splicing using modified oligonucleotides

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

Modification of MyD88 splicing using modified oligonucleotides

Oligomeric compounds and compositions for use in modulation of small non-coding RNAs

Interative, preferably computer based iterative processes for generating synthetic compounds with desired physical, chemical and/or bioactive properties, i.e., active compounds, are provided. During iterations of the processes, a target nucleic acid sequence is provided or selected, and a library of candidate nucleobase sequences is generated in silico according to defined criteria. A 'virtual' oligonucleotide chemistry is chosen and a library of virtual oligonucleotide compounds having the selected nucleobase sequences is generated. These virtual compounds are reviewed and compounds predicted to have particular properties are selected. The selected compounds are robotically synthesized and are preferably robotically assayed for a desired physical, chemical or biological activity. Active compounds are thus generated and, at the same time, preferred sequences and regions of the target nucleic acid that are amenable to oligonucleotide or sequence-based modulation are identified.

System of components for preparing oligonucleotides

Compositions and methods for the treatment of asthma with oligonucleotides which specifically hybridize with nucleic acids encoding B7 proteins.

Oligonucleotide compositions and methods for the modulation of the expression of B7 protein

Compositions and methods for the diagnosis, prevention and treatment of immune states and disorders amenable to treatment through modulation of T cell activation are provided. In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with nucleic acids encoding B7 proteins.

Antisense modulation of B7 protein expression

Modified oligonucleotides having a GGG motif sequence and a sufficient number of flanking nucleotides to modulate the telomere length of a chromosome are provided. Methods of modulating telomere length of a mammalian chromosome in vitro and in vivo are also provided, as are methods for inhibiting the division of a malignant mammalian cell and for modulating the effects of cellular aging.

Modulation of telomere length by oligonucleotides having a G-core sequence

Methods for modulating expression of a gene are provided. The methods comprise the steps of selecting a portion of an RNA coded by the gene, wherein the RNA is capable of interacting with a protein, preparing an oligonucleotide or oligonucleotide analog to mimic the portion of the RNA, and contacting cells containing the gene with the oligonucleotide or oligonucleotide analog. Methods of treating a disease are also provided. The methods comprise selecting a portion of an RNA coded by a gene whose expression is believed to be responsible for the disease, preparing an oligonucleotide or oligonucleotide analog to mimic the portion, and contacting an organism suspected of having the disease with the oligonucleotide or oligonucleotide analog.

Reagents and methods for modulating gene expression through RNA mimicry

Oligonucleotide compositions and methods for the modulation of the

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Oceanside, CA, United States of America

Timothy A Vickers