Isis Pharmaceuticals, Inc.

Ionis Pharmaceuticals, Inc.

Robert McKay

Brett P Monia

Sanjay Bhanot

Kenneth W Dobie

Eric E Swayze

Punit P Seth

Jacqueline R Wyatt

Andrew M Siwkowski

Richard S Geary

Edward Wancewicz

Susan M Freier

Nicholas M Dean

Madeline M Butler

Lex M Cowsert

Brenda F Baker

William A Gaarde

Pamela S Nero

Sanjay K Pandey

C Frank Bennett

Ravi Jain

James G Karras

Loren J Miraglia

Muthiah Manoharan

Murielle M Veniant-Ellison

Xing-Xian Yu

Richard A Lindberg

Alexander H Borchers

Lynnetta Watts

John G Geisler

John R Shutter

Stanley T Cooke

Madelline M Butler

Trisha Lockhart

Namir Sioufi

The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing.

Compounds and methods for modulating gene expression

Short antisense compounds with gapmer configuration

Compounds and methods for modulating expression of DGAT2

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

The present invention relates to novel chimeric oligomeric compounds having a plurality of alternating regions having either RNA like having northern or 3'-endo conformational geometry (3&#x2032;-endo regions) or DNA like having southern or C2&#x2032;-endo/O4&#x2032;-endo conformational geometry. The oligomeric compounds of the present invention have shown reduction in mRNA levels in multiple in vitro and in vivo assay systems and are useful, for example, for investigative and therapeutic purposes.

Chimeric oligomeric compounds comprising alternating regions of northern and southern conformational geometry

Compounds and methods for modulating expression ApoB

Compounds, compositions and methods are provided for modulating the expression of glucagon receptor. The compositions comprise oligonucleotides, targeted to nucleic acid encoding glucagon receptor. Methods of using these compounds for modulation of glucagon receptor expression and for diagnosis and treatment of disease associated with expression of glucagon receptor are provided.

Modulation of glucagon receptor expression

Compounds and methods for modulating expression of PTP1B

Antisense compounds, compositions and methods are provided for modulating the expression of forkhead box O1A. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding forkhead box O1A. Methods of using these compounds for modulation of forkhead box O1A expression and for treatment of diseases associated with expression of forkhead box O1A are provided, in particular, for methods of treating diabetes.

Modulation of forkhead box O1A expression

Compounds and methods for modulating expression of GCCR

Compounds and methods for modulating expression of SGLT2

Disclosed herein are compounds, compositions and methods for modulating the expression of ACC1 or ACC2 or both in a cell, tissue or animal. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders.

Compositions and their uses directed to acetyl-CoA carboxylases

Disclosed herein are compounds, compositions and methods for modulating the expression of PTPRU in a cell, tissue or animal. Also provided are methods of active target segment validation. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. Also provided are methods for the prevention, amelioration and/or treatment of diabetes, obesity, insulin resistance, insulin deficiency, hypercholesterolemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hyperfattyacidemia, liver steatosis, steatohepatitis, non-alcoholic steatohepatitis, metabolic syndrome, cardiovascular disease and coronary heart disease by administration of antisense compounds targeted to PTPRU.

Compositions and their uses directed to PTPRU

Compounds and methods for modulating expression of GCGR

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Poway, CA, United States of America

Robert McKay