Abstract: 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.

Abstract: Provided herein are methods for regenerating hair cells in an adult mammalian inner ear using novel combinations of agents selected from the group consisting of a histone deacetylase (HDAC) inhibitor, one or more inhibitory nucleic acids targeting Fir, Mxi1, Fbxw7, or a combination thereof, a Wnt pathway activator, and a cAMP activator. The methods and compositions can be used to treat a subject with hearing loss or vestibular dysfunction.

Abstract: A package structure including a semiconductor die, a redistribution circuit structure and an electronic device is provided. The semiconductor die is laterally encapsulated by an insulating encapsulation. The redistribution circuit structure is disposed on the semiconductor die and the insulating encapsulation. The redistribution circuit structure includes a colored dielectric layer, inter-dielectric layers and redistribution conductive layers embedded in the inter-dielectric layers. The electronic device is disposed over the colored dielectric layer and electrically connected to the redistribution circuit structure.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: Compositions for the prevention, treatment and/or reversal of hearing loss include vectors encoding an Islet-1 (Isl1) nucleic acid sequence. The over-expression of Isl1 molecules in ear cells, for example, hair cells, results in the treatment of hearing loss due to age, noise exposure or any idiopathic causes.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: Disclosed are compositions and methods that useful in the treatment and/or prevention of hearing loss caused by genetic mutation of the TMPRSS3 gene or the LOXHD1 gene. The compositions and methods disclosed herein use adeno-associated viral (AAV) vector gene delivery of TRMPSS3 or LOXHD1 into the inner ear to restore activity of the TMPRSS3 gene or the LOXHD1 gene, respectively, promote hair cell survival and restore hearing in patients suffering from hearing loss.

Abstract: 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.

Abstract: 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.

Abstract: Compositions for the prevention, treatment and/or reversal of hearing loss include vectors encoding an Islet-1 (Isl1) nucleic acid sequence. The over-expression of Isl1 molecules in ear cells, for example, hair cells, results in the treatment of hearing loss due to age, noise exposure or any idiopathic causes.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.