Isis Pharmaceuticals, Inc.

Ionis Pharmaceuticals, Inc.

Cold Spring Harbor Laboratory

Biogen Ma Inc.

Other

The Johns Hopkins University

University of California

University of Utah Research Foundation

Washington University

The Penn State Research Foundation

University of Texas System

Northwestern University

University of British Columbia

Baylor College of Medicine

Ludwig Institute for Cancer Research Limited

C Frank Bennett

Susan M Freier

Lex M Cowsert

Nicholas M Dean

Richard Holmes Griffey

Frank Rigo

Gene Hung

Eric E Swayze

Kenneth W Dobie

Brenda F Baker

Eric G Marcusson

Seng H Cheng

Jacqueline R Wyatt

Don W Cleveland

Elizabeth J Ackermann

Brett P Monia

Lamya S Shihabuddin

Timothy A Vickers

Christopher K Mirabelli

Christine Esau

Thomas P Condon

Holly Kordasiewicz

Lisa Stanek

Andrew T Watt

Adrian R Krainer

Noga Yerushalmi

Ayelet Chajut

Stanley T Crooke

Ravi Jain

Balkrishen Bhat

Erich Koller

Niall O'Donnell

J Gordon Foulkes

Bridget Lollo

Shin Cheng Flournoy

David J Ecker

Robert McKay

James G Karras

Kevin P Anderson

Allan Lipton

Yimin Hua

Sarah Greenlee

Lois Mary Witters

Brian J Nickoloff

Susan M Frier

Philip L Felgner

Ryszard M Kole

Stefan M Pulst

Casey Kopczynski

Robert A MacLeod

Marco A Passini

Ronnie C Hanecak

Madeline M Butler

Xue-hai Liang

Katherine W Klinger

Vickie L Brown-Driver

Janet M Leeds

Daniel R Scoles

David L Spector

Timothy M Miller

Ming-Yi Chiang

Rahul Sinha

Eigen Peralta

Constantin Van Outryve D'Ydewalle

Muthiah Manoharan

Phillip Dan Cook

Thazha P Prakash

Steven A Hofstadler

Rangarajan Sampath

Hong Zhang

Bert W O'Malley

Andrew M Siwkowski

Takashi Kei Kishimoto

Huynh-Hoa Bui

Michael R Hayden

William A Gaarde

Michelle L Hastings

Glenn D Hoke

Richard Alan Smith

Mark E Swanson

Joshua N Finger

Jeffrey D Rothstein

Sanjay K Pandey

Wen Shen

Thomas A Mustoe

Harris Busch

Jordan S Pober

Ssucheng Jeff Hsu

Loren J Miraglia

Bruce M Wentworth

Russell T Boggs

Kristin Sannes Lowery

Stanislaw M Stepkowski

Charles A Thornton

Jeffrey Carroll

Simon Warby

Zhenxun Wang

Edgardo Baracchini, Jr

Andrew Leger

Vivian Qingqing Zhang

Disclosed herein are antisense compounds and methods for selectively reducing expression of an allelic variant of a gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate diseases, including neurodegenerative diseases, such as Huntington's Disease (HD).

Selective reduction of allelic variants

Disclosed herein are antisense compounds and methods for decreasing Ataxin 2 mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate Ataxin 2 associated diseases, disorders, and conditions. Such Ataxin 2 associated diseases include spinocerebellar ataxia type 2 (SCA2), amyotropic sclerosis (ALS), and parkinsonism.

Compositions for modulating Ataxin 2 expression

Disclosed herein are methods for reducing expression of Tau mRNA and protein in an animal with Tau antisense compounds. Also disclosed are methods for modulating splicing of Tau mRNA in an animal with Tau antisense compounds. Such methods are useful to treat, prevent, or ameliorate neurodegenerative diseases in an individual in need thereof. Examples of neurodegenerative diseases that can be treated, prevented, and ameliorated with the administration Tau antisense oligonucleotides include Alzheimer's Disease, Fronto-temporal Dementia (FTD), FTDP-17, Progressive Supranuclear Palsy, Chronic Traumatic Encephalopathy, Epilepsy, and Dravet's Syndrome.

Methods for treating Alzheimer's disease

Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject.

Compositions and methods for modulation of SMN2 splicing in a subject

In certain embodiments, the present disclosure provides methods comprising contacting a cell with a compound comprising a modified oligonucleotide complementary to a nucleic acid transcript. In certain such embodiments, the modified oligonucleotide does not interact or interacts poorly with a mRNP complex or granule. In certain such embodiments the modifications and/or motifs of the modified oligonucleotide do not promote interaction with a mRNP complex or granule. In certain embodiments, the present disclosure provides methods comprising contacting a cell with a compound comprising a modified oligonucleotide thereby reducing the size or amount of protein aggregation in the cell. In certain such embodiments, the protein aggregate is a mRNP granule. In certain such embodiments, the modifications and/or motifs of the modified oligonucleotide promote interaction with a protein aggregate, such as a mRNP granule, that results in disruption of the protein aggregate.

Compositions and methods for modulation of protein aggregation

Provided herein are methods, compounds, and compositions for reducing expression of huntingtin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate Huntington's disease, or a symptom thereof.

Modulation of Huntington expression

The present disclosure provides compounds comprising modified oligonucleotides for use in CRISPR. In certain embodiments, such modified oligonucleotides provide improved properties of crRNA. In certain embodiments, such modified oligonucleotides provide improved properties of scrRNA.

Modified CRISPR RNA and modified single CRISPR RNA and uses thereof

The present invention provides compounds comprising oligonucleotides complementary to a pyruvate kinase M transcript. Certain such compounds are useful for hybridizing to a pyruvate kinase M transcript, including but not limited to a pyruvate kinase M transcript in a cell. In certain embodiments, such hybridization results in modulation of splicing of the pyruvate kinase M transcript. In certain embodiments, such compounds are used to treat one or more symptoms associated with cancer.

Antisense compounds and uses thereof

Certain embodiments are directed to methods and compounds for modulating expression of SMN. In certain embodiments at least two compounds are used: a first compound for inhibiting SMN-NAT and increasing expression of SMN, and a second compound for modulating the splicing of SMN. Such methods and compounds are useful for increasing expression exon 7 containing SMN mRNA in cells and animals.

Combinations for the modulation of SMN expression

Disclosed herein are compositions and methods for reducing expression of C9ORF72 antisense transcript in an animal with C9ORF72 antisense transcript specific inhibitors. Such methods are useful to treat, prevent, or ameliorate neurodegenerative diseases in an individual in need thereof. Such C9ORF72 antisense transcript specific inhibitors include antisense compounds.

Methods for modulating expression of C9ORF72 antisense transcript

The present disclosure provides compounds comprising oligonucleotides complementary to a portion of the IKBKAP gene. Certain such compounds are useful for hybridizing to a portion of the IKBKAP gene, including but not limited to a portion of the IKBKAP gene in a cell. In certain embodiments, such hybridization results in modulation of splicing of the IKBKAP gene. In certain embodiments, the IKBKAP gene includes a mutation that results in defective splicing and a truncated IKAP protein. In certain embodiments, hybridization of oligonucleotides complementary to a portion of the IKBKAP gene results in a decrease in the amount of defective splicing and truncated IKAP protein. In certain embodiments, hybridization of oligonucleotides complementary to a portion of the IKBKAP gene results in an increase in the amount of normal splicing and functional, full-length IKAP protein. In certain embodiments, oligonucleotides are used to treat Familial Dysautonomia.

Compositions and methods for modulation of IKBKAP splicing

Provided herein are methods, compounds, and compositions for reducing expression of a MaTAR in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate breast cancer in an individual in need.

Methods of treating breast cancer

Certain embodiments are directed to methods and compounds for inhibiting SMN-NAT, the natural antisense transcript of SMN. Such methods and compounds are useful for increasing expression of SMN in cells and animals.

Modulation of SMN expression

Modulation of huntingtin expression

Disclosed herein are compounds, compositions and methods for modulating the expression of huntingtin in a cell, tissue or animal. Further provided are methods of slowing or preventing Huntington's disease progression using an antisense compound targeted to huntingtin. Additionally provided are methods of delaying or preventing the onset of Huntingtin's disease in an individual susceptible to Huntingtin's Disease. 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 huntingtin

Growing community of inventors

Carlsbad, CA, United States of America

C Frank Bennett