Regeneron Pharmaceuticals, Inc.

Decibel Therapeutics, Inc.

Regeneran Pharmaceuticals, Inc.

Meghan Drummond Samuelson

Andrew J Murphy

Brian Zambrowicz

David Frendewey

Aris I Baras

Christos Kyratsous

Manuel Allen Revez Ferreira

Goncalo Abecasis

Kavita Praveen

Giovanni Coppola

Lauren Gurski

Leah Sabin

Kathryn Ellis

Martin Schwander

Jonathon Whitton

Joseph Burns

Adam Palermo

Jeffery Haines

Ka-Man Venus Lai

Jose F Rojas

Susan D Croll

Nicole M Alessandri-Haber

Claudia Gonzaga-Jauregui

Charleen Hunt

Suzanne Hartford

Susannah Brydges

Robert Breese

Keith Crosby

The disclosure features compositions and methods for the treatment of sensorineural hearing loss and auditory neuropathy, particularly forms of the disease that are associated with mutations in otoferlin (OTOF), by way of OTOF gene therapy. The disclosure provides a variety of compositions that include a first nucleic acid vector that contains a polynucleotide encoding an N-terminal portion of an OTOF protein and a second nucleic acid vector that contains a polynucleotide encoding a C-terminal portion of an OTOF protein. These vectors can be used to increase the expression of OTOF in a subject, such as a human subject suffering from sensorineural hearing loss.

Compositions and methods for treating sensorineural hearing loss using otoferlin dual vector systems

The present disclosure provides methods of treating subjects having hearing loss, methods of identifying subjects having an increased risk of developing hearing loss, and methods of detecting Kelch Domain Containing 7B (KLHDC7B) variant nucleic acid molecules and variant polypeptides.

Kelch domain containing 7B (KLHDC7B) variants and uses thereof

The disclosure provides polynucleotides containing regions of the Myosin 15 (Myo15) promoter, as well as vectors containing the same, that can be used to promote expression of a transgene specifically in hair cells. The polynucleotides described herein may be operably linked to a transgene, such as a transgene encoding a therapeutic protein, so as to promote hair cell-specific expression of the transgene. The polynucleotides described herein may be operably linked to a therapeutic transgene and used for the treatment of subjects having or at risk of developing hearing loss or vestibular dysfunction.

Myosin 15 promoters and uses thereof

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized TTR locus and methods of using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized TTR locus express a human transthyretin protein or a chimeric transthyretin protein, fragments of which are from human transthyretin. Methods are provided for using such non-human animals comprising a humanized TTR locus to assess in vivo efficacy of human-TTR-targeting reagents such as nuclease agents designed to target human TTR. Methods are also provided for making such non-human animals comprising a humanized TTR locus.

Non-human animals comprising a humanized TTR locus and methods of use

Non-human animal cells and non-human animals comprising a humanized TTR locus comprising a beta-slip mutation and methods of using such non-human animal cells and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized TTR locus comprising a beta-slip mutation express a human transthyretin protein or a chimeric transthyretin protein, fragments of which are from human transthyretin. Methods are provided for using such non-human animals comprising a humanized TTR locus to assess in vivo efficacy of human-TTR-targeting reagents such as nuclease agents designed to target human TTR.

Mouse comprising a humanized TTR locus with a beta-slip mutation and methods of use

This disclosure relates to an animal model of human disease. More specifically, this disclosure relates to a rodent model of mood disorders such as unipolar depression and an anxiety disorder. Disclosed herein are genetically modified rodent animals that carry a humanized G protein-coupled receptor 156 (GPR156) gene that encodes a mutant human GPR156 protein comprising Asp at an amino acid position corresponding to position 533 in a full length wild type human GPR156 protein.

Rodent model of mood disorders

Growing community of inventors

Katonah, NY, United States of America

Meghan Drummond Samuelson