Isis Pharmaceuticals, Inc.

Other

University of Utah Research Foundation

Isis Phramaceuticals, Inc.

Jacqueline R Wyatt

Susan M Freier

Brett P Monia

Lex M Cowsert

C Frank Bennett

David J Ecker

Robert McKay

Madeline M Butler

Timothy A Vickers

Kevin P Anderson

Ronnie C Hanecak

Peter W Davis

Brenda F Baker

Vickie L Brown-Driver

John S Kiely

Oscar L Acevedo

Normand Hebert

Ian Popoff

Kenneth W Dobie

Sanjay Bhanot

Thomas W Bruice

Ming-Yi Chiang

Olga Matveeva

Alexander Tsodikov

Jean Louis Imbach

Michael C Giddings

Muthiah Manoharan

Phillip Dan Cook

Stanley T Crooke

Nicholas M Dean

Hong Zhang

Kenneth G Draper

Yogesh S Sanghvi

John McNeil

Eric G Marcusson

Christopher K Mirabelli

James G Karras

Donna T Ward

William A Gaarde

Michael J Weber

Susan F Murray

Harris Busch

Alexander H Borchers

Henri M Sasmor

Cara Ohashi

Madelline M Butler

Scott E Davis

Stanley T Cooke

Douglas G Brooks

Robert Mckay

Compounds, compositions and methods are provided for modulating the expression of PTP1B. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PTP1B. Methods of using these compounds for modulation of PTP1B expression and for treatment of diseases associated with expression of PTP1B are provided.

Antisense modulation of PTP1B expression

Methods for obtaining antisense oligonucleotides with activity against a desired target are provided. Methods of identifying oligonucleotide sequence motifs which are predictive of antisense oligonucleotide activity are provided, as are motifs identified according to this method. Methods of selecting effective antisense oligonucleotide sequences and effective antisense target sequences are provided, as are sequences selected according to these methods. In other methods of the invention, oligonucleotides are designed to hybridize to target sequences containing one or more activity-enhancing motifs. Antisense oligonucleotides designed according to these methods are also provided.

Methods of obtaining active antisense compounds

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

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

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

Antisense modulation of polo-like kinase expression

Antisense compounds, compositions and methods are provided for modulating the expression of Damage-specific DNA binding protein 1, p127. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Damage-specific DNA binding protein 1, p127. Methods of using these compounds for modulation of Damage-specific DNA binding protein 1, p127 expression and for treatment of diseases associated with expression of Damage-specific DNA binding protein 1, p127 are provided.

Antisense modulation of damage-specific DNA binding protein 1, p127 expression

Antisense compounds, compositions and methods are provided for modulating the expression of EDG1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding EDG1. Methods of using these compounds for modulation of EDG1 expression and for treatment of diseases associated with expression of EDG1 are provided.

Antisense modulation of EDG1 expression

Compounds, compositions and methods are provided for inhibiting Fas mediated signaling. The compositions comprise antisense compounds targeted to nucleic acids encoding Fas, FasL and Fap-1. Methods of using these antisense compounds for inhibition of Fas, FasL and Fap-1 expression and for treatment of diseases, particularly autoimmune and inflammatory diseases and cancers, associated with overexpression or constitutive activation of Fas, FasL or Fap-1 are provided.

Antisense modulation of Fas mediated signaling

Antisense compounds, compositions and methods are provided for modulating the expression of Protein Phosphatase 2 catalytic subunit beta. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Protein Phosphatase 2 catalytic subunit beta. Methods of using these compounds for modulation of Protein Phosphatase 2 catalytic subunit beta expression and for treatment of diseases associated with expression of Protein Phosphatase 2 catalytic subunit beta are provided.

Antisense modulation of protein phosphatase 2 catalytic subunit beta expression

Antisense compounds, compositions and methods are provided for modulating the expression of CD40 ligand. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding CD40 ligand. Methods of using these compounds for modulation of CD40 ligand expression and for treatment of diseases associated with expression of CD40 ligand are provided.

Antisense modulation of CD40 ligand expression

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Encinitas, CA, United States of America

Jacqueline R Wyatt