Cold Spring Harbor Laboratory

Ionis Pharmaceuticals, Inc.

Isis Pharmaceuticals, Inc.

Stoke Therapeutics, Inc.

Biogen Ma Inc.

Adrian R Krainer

C Frank Bennett

Frank Rigo

Isabel Aznarez

Yimin Hua

Seng H Cheng

Brenda F Baker

Huw M Nash

Gene Hung

Lamya S Shihabuddin

Marco A Passini

Katherine W Klinger

Tomoki Nomakuchi

Rahul Sinha

Zhenxun Wang

Luca Cartegni

The present disclosure relates to compositions and methods for inhibiting nonsense-mediated mRNA decay in a gene-specific manner, for example in the treatment of diseases or disorders caused by nonsense mutations.

Reducing nonsense-mediated MRNA decay

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

Provided herein are methods and compositions for increasing the expression of a protein, and for treating a subject in need thereof, e.g., a subject with deficient protein expression or a subject having a disease described herein.

Antisense oligomers and uses thereof

Provided herein are methods and compositions for treating a subject in need thereof, such as a subject with deficient SYNGAP1 protein or SCN1A protein expression or a subject having AD mental retardation 5 or Dravet syndrome.

Antisense oligomers for treatment of autosomal dominant mental retardation-5 and Dravet Syndrome

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 and compositions for increasing production of a target protein or functional RNA by a cell.

Targeted augmentation of nuclear gene output

Reducing nonsense-mediated mRNA decay

Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy.

Compositions and methods for modulation of SMN2 splicing in a subject

Provided herein are antisense compounds and methods for recruiting one or more non-cleaving protein to a target nucleic acid in a cell. In certain instances such recruitment of a non-cleaving protein alters the function or activity of the target nucleic acid. In certain such instances, the target nucleic acid a pre-mRNA and the recruitment of the non-cleaving protein results in a change in splicing of the pre-mRNA.

Compounds and methods for modulating interaction between proteins and target nucleic acids

Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA 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, including spinal muscular atrophy.

Growing community of inventors

Huntington Square, NY, United States of America

Adrian R Krainer