Isis Pharmaceuticals, Inc.

Regulus Therapeutics Inc.

Ionis Pharmaceuticals, Inc.

Merck + Co., Inc.

Eli Lilly and Company

Translate Bio, Inc.

Other

Merck Sharp + Dohme Corp.

Sanofi

Balkrishen Bhat

Eric E Swayze

Thazha P Prakash

Charles Allerson

Richard Holmes Griffey

Muthiah Manoharan

Anne Bettina Eldrup

Brenda F Baker

Phillip Dan Cook

Punit P Seth

Eric G Marcusson

Christine Esau

Garth A Kinberger

Susan M Freier

C Frank Bennett

David Brian Olsen

Andrew M Siwkowski

Ravi Jain

Deidre A MacKenna

Jeremy Duffield

Stanley T Crooke

Kenneth W Dobie

Michael T Migawa

David P Bartel

Walter F Lima

Jeremy Graff

Bridget Lollo

Malcolm MacCoss

Malcolm Maccoss

Timothy A Vickers

Marija Prhavc

Quanlai Song

Vasulinga T Ravikumar

Akin Akinc

Andrei P Guzaev

Gabor Butora

Haoyun An

Charles John Guinosso

Daniel J Hogan

Prasad Dande

Steven S Carroll

Neil W Gibson

Brandee Wagner

Diedre MacKenna

Erich Koller

Saswata Karmakar

Jia Tay

Nelson Chau

Eigen Peralta

Clarence Frank Bennett

Normand Hebert

Bharvin Kumar Patel

Hongjiang Wu

Jie Xia

Robert L LaFemina

Tadeusz Krzysztof Wyrzykiewicz

Amy L Simcoe

Joanne E Tomassini

Fatih Ozsolak

Guillermo Vasquez

Dawn L Hall

Neelima Bhat

Bryan A Kraynack

Andrei P Guzzaev

Bridget Gordon

Peter Linsley

Debatosh Majumdar

Joshua Nichols

Mario A Valenciano

Carrie A Rutkowski

Ann B Eldrup

Philip Dan Cook

Amy L Himmelberger

Anne B Eldrup

Robert L Lafemina

Lawrence C Kuo

Deidre Mackenna

Daniel Hogan

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

Aspects of the disclosure relate to particle formulations, e.g., nanoparticle formulations, methods of making particle formulations, and methods for delivery of oligonucleotides and/or synthetic RNA, e.g., for increasing gene expression in a targeted manner. In some embodiments, compositions and methods are provided that are useful for posttranscriptionally altering protein and/or RNA levels in a targeted manner. Aspects of the disclosure described herein provide compositions and methods that are useful for protecting RNAs from degradation (e.g., exonuclease mediated degradation).

Nanoparticle formulations for delivery of nucleic acid complexes

Provided herein are compositions and methods for facilitating or enhancing delivery of nucleic acids, such as synthetic mRNAs, into cells or tissues. Such compositions and methods may include use of a targeting moiety-conjugated, such as an N-acetylgalactosamine (GalNAc)-conjugated, oligonucleotide to facilitate or enhance delivery.

Compositions and methods for facilitating delivery of synthetic nucleic acids to cells

Provided herein are conjugates comprising targeting moieties such as sugars, folates and cell-penetrating peptides, which can be used for the improved delivery of agents (e.g., nucleic acids, such as oligonucleotides or mRNAs, or other agents) to cells. The invention provides conjugates and compounds comprising targeting moieties, methods for preparing the same, and intermediates useful in their preparation. In another aspect, the present invention provides formulations (e.g., pharmaceutical compositions) comprising the targeting moiety-containing conjugates and compounds. The present invention also provides methods for delivering agents (e.g., nucleic acids such as oligonucleotides or mRNAs) to a cell, methods for treating and/or preventing a disease or condition in a subject, and methods for modulating gene expression in a cell or a subject. Further, provided herein are kits comprising the conjugates, or formulations thereof; and kits for the preparation of conjugates described herein.

Nucleic acid conjugates and uses thereof

The present invention provides compositions comprising at least one oligomeric compound comprising an alternating motif and further include a region that is complementary to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.

Compositions comprising alternating 2'-modified nucleosides for use in gene modulation

Described herein are conjugated modified oligonucleotides that are complementary to a target RNA. The conjugate facilitates cellular uptake of the modified oligonucleotide, resulting improved potency.

Compounds and methods for enhanced cellular uptake

Described herein are compositions and methods for the inhibition of miR-122 activity. The compositions have certain nucleoside modifications that yield potent inhibitors of miR-122 activity. The compounds may comprise conjugates to facilitate delivery to the liver. The compositions may be administered to subjects infected with hepatitis C virus, as a treatment for hepatitis C virus and related conditions.

MicroRNA compounds and methods for modulating miR-122

Described herein are compounds comprising modified oligonucleotides that are complementary to miR-103 and/or miR-107 and methods of treating diseases and disorders using the compounds.

Targeting microRNAs for metabolic disorders

Described herein are compositions and methods for the inhibition of miR-21 activity. The compositions have certain nucleoside modifications that yield potent inhibitors of miR-21 activity. The compounds may comprise conjugates to facilitate delivery to the liver. The compositions may be administered to subjects with liver conditions, such as liver cancer.

MicroRNA compounds and methods for modulating miR-21 activity

Provided herein are methods for the treatment of Alport Syndrome, using modified oligonucleotides targeted to miR-21. In certain embodiments, a modified oligonucleotide targeted to miR-21 improves kidney function and/or reduces fibrosis in subjects having Alport Syndrome. In certain embodiments, administration of a modified oligonucleotide targeted to miR-21 delays the onset of end-stage renal disease in a subject having Alport Syndrome. In certain embodiments, a modified oligonucleotide targeted to miR-21 delays the need for dialysis or kidney transplant in a subject having Alport Syndrome.

Methods for treatment of alport syndrome

Microrna compounds and methods for modulating MIR-21 activity

Growing community of inventors

Carlsbad, CA, United States of America

Balkrishen Bhat