Regulus Therapeutics Inc.

Rosetta Genomics Ltd.

Isis Pharmaceuticals, Inc.

Ionis Pharmaceuticals, Inc.

Christine Esau

C Frank Bennett

Eric G Marcusson

Noga Yerushalmi

Ayelet Chajut

Eric E Swayze

Balkrishen Bhat

Garth A Kinberger

Susan M Freier

Richard Holmes Griffey

Sanjay Bhanot

Brenda F Baker

Timothy A Vickers

Ravi Jain

Erich Koller

Bridget Lollo

Eigen Peralta

Frank C Bennett

Scott E Davis

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

Methods are provided for the treatment of cardiovascular or metabolic diseases characterized by elevated serum total cholesterol, elevated serum LDL-cholesterol, or elevated serum triglycerides, through the administration of an oligomeric compound which modulates the levels or activity of miR-122a. Further provided are methods for reducing hepatic steatosis or liver tissue triglyceride accumulation through the administration of an oligomeric compound which modulates the levels or activity of miR-122a. Such methods employ oligomeric compounds which hybridize with or sterically interfere with nucleic acid molecules comprising or encoding miR-122a. Such oligomeric compounds may include one or more modifications thereon, which may improve the activity, stability, or nuclease resistance of the oligomeric compound. These modified oligomeric compounds are used as single compounds or in compositions, including pharmaceutical compositions, to modulate or mimic the targeted nucleic acid comprising or encoding miR-122a.

Methods for use in modulating miR-122A

Targeting microRNAS for the treatment of liver cancer

Compounds, compositions and methods are provided for modulating the levels expression, processing and function of miRNAs. The compositions comprise oligomeric compounds targeted to small non-coding RNAs and miRNAs. The oligomeric compounds possess potent miRNA inhibitory activity, and further exhibit improved therapeutic index. Further provided are methods for selectively modulating miRNA activating in a cell.

Oligomeric compounds and compositions for the use in modulation of micrornas

Compounds, compositions and methods are provided for modulating the levels expression, processing and function of miRNAs. The compositions comprise oligomeric compounds targeted to small non-coding RNAs and miRNAs. The oligomeric compounds possess potent miRNA inhibitory activity, and further exhibit improved therapeutic index. Further provided are methods for selectively modulating miRNA activing in a cell.

Oligomeric compounds and compositions for the use in modulation of target nucleic acids

Methods for use in modulating miR-122a

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

Compounds, compositions and methods are provided for modulating the levels expression, processing and function of miRNAs. The compositions comprise oligomeric compounds targeted to small non-coding RNAs and miRNAs. The oligomeric compounds possess potent miRNA inhibitory activity, and further exhibit improved therapeutic index. Further provided are methods for selectively modulating miRNA activity in a cell.

Oligomeric compounds and compositions for the use in modulation of microRNAs

Provided herein are methods for detection of miRNA in a sample. In certain embodiments, the sample comprises RNA and is derived from a cell or tissue. The methods of detection employ a competitor molecule to allow for detection of an miRNA in the presence of an anti-miRNA oligonucleotide.

MicroRNA detection

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

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La Jolla, CA, United States of America

Christine Esau