Massachusetts Eye and Ear Infirmary

Harvard College

Rescue Hearing Inc.

Zheng-Yi Chen

David R Liu

David B Thompson

John Zuris

Margie Li

Wenyan Li

Yi-Zhou Quan

Albena Kantardzhieva

Hinrich Staecker

Mingqian Huang

Caesar James Ayala

Xue Zhong Liu

David Thompson

David Liu

Compositions for regeneration of inner cells and for treating hearing loss comprise at least one modulator of mechanistic target of rapamycin (mTOR) sufficient to induce reprogramming proliferation and regeneration of inner ear cells. The composition include, in some instances, an effective amount of one or more phosphatase and tensin homolog (PTEN) inhibitors, MYC/NOTCH modulators, Atonal Homolog 1 (Atoh1) modulators or combinations thereof.

Treatment of hearing loss

Provided are methods and compositions for inducing cells of the inner ear (for example, cochlear and utricular hair cells) to reenter to cell cycle and to proliferate. More particularly, the invention relates to the use of agents that increase c-myc activity and/or Notch activity for inducing cell cycle reentry and proliferation of cochlear or utricular hair cells and/or cochlear or utricular supporting cells. The methods and compositions can be used to promote the proliferation of hair cells and/or supporting cells to treat a subject at risk of, or affected with, hearing loss or a subject at risk of, or affected with vestibular dysfunction.

Methods and compositions for regenerating hair cells and/or supporting cells

Compositions are described for direct protein delivery into multiple cell types in the mammalian inner ear. The compositions are used to deliver protein(s) (such as gene editing factors) editing of genetic mutations associated with deafness or associated disorders thereof. The delivery of genome editing proteins for gene editing and correction of genetic mutations protect or restore hearing from genetic deafness. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

Methods for efficient delivery of therapeutic molecules in vitro and in vivo

Compositions and provided to induce cells of the inner ear to renter the cell cycle and to proliferate. In particular, hair cells are induced to proliferate by administration of a composition which activates the Myc and Notch. Supporting cells are induced to transdifferentiate to hair cells by inhibition of Myc and Notch activity or the activation of Atoh1. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

Efficient delivery of therapeutic molecules to cells of the inner ear

Method for efficient delivery of therapeutic molecules in vitro and in vivo

Described are methods and compositions for increasing islet-1 (Isl1) activity (e.g., biological activity) and or expression (e.g., transcription and/or translation) in a biological cell and or in a subject.

Islet1 (ISl1) and hearing loss

A chimeric molecule of one or more proteins or peptides fused, complexed or linked to one or more anionic molecules. Efficient in vitro and in vivo delivery is attained by encapsulating these molecules in cationic lipids or cationic liposomes. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

Efficient delivery of therapeutic molecules in vitro and in vivo

Islet1 (Isl1) and hearing loss

Growing community of inventors

Somerville, MA, United States of America

Zheng-Yi Chen