Regulus Therapeutics Inc.

Isis Pharmaceuticals, Inc.

Rosetta Genomics Ltd.

Eli Lilly and Company

Jaan Biotherapeutics LLC

Ionis Pharmaceuticals, Inc.

Universitat De Valéncia

The Florey Institute of Neuroscience and Mental Health

Arthex Biotech S.l.

Eric G Marcusson

C Frank Bennett

Balkrishen Bhat

Christine Esau

Susan M Freier

Kenneth W Dobie

Ayelet Chajut

Eric E Swayze

Richard Holmes Griffey

Thazha P Prakash

Noga Yerushalmi

Nicholas M Dean

Jeremy Graff

Brenda F Baker

Timothy A Vickers

Ravi Jain

Donna T Ward

Youngsoo Kim

Erich Koller

Sanjay Bhanot

Akin Akinc

Jacqueline R Wyatt

Charles Allerson

Bridget Lollo

Bhawanjit Kaur Brar

Scott W Henry

Eigen Peralta

Robert A MacLeod

Elizabeth J Ackermann

Garth A Kinberger

Sanjay K Pandey

Ranjan Perera

Steven Petrou

Ssucheng Jeff Hsu

Estefanía Cerro Herreros

Nerea Moreno Cervera

Irene González Martínez

Rubén Artero Allepuz

María Beatriz Llamusí Troisi

Peter Linsley

Seongjoon Koo

Robert A Macleod

The invention provides oligonucleotide and/or oligonucleotide analogue molecules that are antagonists of a microRNA, preferably antagonists of human microRNAs hsa-miR-23b-3p and hsa-miR-218-5p, that comprise a mixture of phosphorothioate and phosphodiester linkages, and that are conjugated to at least one oleic acid molecule. Inhibiting these microRNAs allows to increase the endogenous levels of the corresponding proteins MBNL1 and/or MBNL2. The present invention further provides compositions comprising said oligonucleotides and/or oligonucleotide analogue molecules and their uses for the treatment and prevention of DM in a subject in need thereof.

Oligonucleotides conjugated to oleic acid and uses thereof

Described herein are compositions and methods that are used to increase the expression of SCN2A, which may be used to treat neurological or psychiatric disorders. Antisense oligonucleotides that target upstream open reading frames (uORFs) may be administered to prevent translation initiation from a uORF to increase expression from a primary ORF (pORF), thus increasing the levels of SCN2A protein.

Compositions and methods for increasing expression of SCN2A

Disclosed herein include microRNA antagonists, therapeutic compositions that include one or more of such microRNA antagonists, and methods of treating and/or ameliorating cardiac diseases and/or muscular dystrophy disorders with the microRNA antagonists. Also included are combination therapies, wherein a therapeutic composition disclosed herein and an additional therapy agent are provided to a subject having or suspected of having cardiac disease and/or muscular dystrophy disorder. In particular, some embodiments disclosed herein relate to compositions and methods for transiently administering a mixture of microRNA antagonists for promoting cardiomyocyte proliferation and cardiac regeneration.

Compositions and methods for treatment of cardiac diseases

Provided herein are methods for the treatment of liver cancer. These methods encompass the administration of a compound comprising a modified oligonucleotide, wherein the modified oligonucleotide is targeted to a miRNA. Also provided herein are compositions for the treatment of liver cancer. Such compositions include compounds comprising a modified oligonucleotide, wherein the modified oligonucleotide is targeted to a miRNA. Certain miRNAs have been identified as overexpressed in liver cancer, such as, for example, hepatocellular carcinoma, and are thus selected for targeting by modified oligonucleotides. Further, certain miRNAs have been identified as overexpressed in hepatocellular carcinoma cells exposed to dioxin, and are thus selected for targeting by modified oligonucleotides. Antisense inhibition of certain of these miRNAs has been found to inhibit cell proliferation and induce apoptosis.

Targeting microRNAs for the treatment of liver cancer

Described herein are compositions and methods for the inhibition of miR-21 activity. The compositions have certain nucleoside modification patterns that yield potent inhibitors of miR-21 activity. The compositions may be used to inhibit miR-21, and also to treat diseases associated with abnormal expression of miR-21, such as fibrosis and cancer.

MicroRNA compounds and methods for modulating miR-21 activity

Targeting microRNAS for the treatment of liver cancer

The present embodiments provide compounds and methods for reducing expression of Metastasis-Associated-in-Lung-Adenocarcinoma-Transcript-1 (MALAT-1) RNA and/or protein in an animal. Such methods are useful for treating cancer, such as colon cancer, intestinal cancer, lung cancer (e.g. non-small cell lung cancer), liver cancer, and/or prostate cancer. In various aspects, the cancer is a primary cancer.

Methods for modulating metastasis-associated-in-lung-adenocarcinoma-transcript-1 (MALAT-1) expression

Provided herein are compositions comprising oligomeric compounds. In certain embodiments, the oligomeric compounds are useful as miRNA mimics. The oligomeric compounds may mimic the activity of miR-34. Also provided herein are methods for the treatment of cancer.

MicroRNA compositions and methods

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

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San Diego, CA, United States of America

Eric G Marcusson