The present disclosure provides constructs comprising a coding sequence operably linked to a promoter, wherein the coding sequence encodes a pendrin protein. Exemplary constructs include AAV constructs. Also provided are methods of using disclosed constructs for the treatment of hearing loss and/or deafness.

This invention relates to polynucleotides encoding mini-dystrophin proteins, viral vectors comprising the same, and methods of using the same for delivery of mini-dystrophin to a cell or a subject.

Methods for treatment and diagnosis of neurological disorders such as autism and autism spectrum disorder are disclosed. Also disclosed are modulators of alternative splicing regulators SRRM4 and/or SRRM3 for treating neurological disorders. Further disclosed are agents that modulate the expression of at least one splice variant for treating neurological disorders. Mouse models of neurological disorders having increased or decreased expression of SRRM4 and/or SRRM3 are also disclosed.

Provided are materials, methods and uses for treating an ophthalmological condition such as Leber Congenital Amaurosis by administering an effective amount of an adeno-associated virus AAV2, serotype 5 (AAV 2/5) or AAV-5 comprising an expressible coding region for human RDH12.

The present invention relates to expression constructs and vectors for the treatment and/or prevention of diseases that are associated with a loss of NPC1 function, such as the lysosomal storage disorder Niemann-Pick type C (NPC) disease.

Disclosed are recombinant meganucleases engineered to bind and cleave a recognition sequence present in a mutant RHO P23H allele. The invention further relates to the use of such recombinant meganucleases in a method for treating retinitis pigmentosa, wherein the mutant RHO P23H allele is preferentially targeted, cleaved, and inactivated.

A method of treating an inherited retinal disease (IRD) associated with a pathogenic point mutation in a mutant allele of an IRD-related gene in the retina or the retinal pigment epithelium (RPE) of a subject in need thereof includes base editing the pathogenic point mutation in the retinal cell or retinal pigment epithelium cell to correct the pathogenic mutation, generate a non-pathogenic point mutation, or modulate expression of an IRD-related gene and restore visual function of subject.

The present invention relates to the use of gasdermin, in particular of gasdermin A, gasdermin B, gasdermin C, gasdermin D, DFNA5 or DFNB59 (or pejvakin), and more particularly pejvakin for modulating cellular redox homeostasis. A particularly preferred use of gasdermin, in particular of gasdermin A, gasdermin B, gasdermin C, gasdermin D, DFNA5 or DFNB59 (or pejvakin), and more particularly pejvakin in the context of the present invention is as an antioxidant. The present invention also concerns a virally-mediated gene therapy for restoring genetically-impaired auditory and vestibular functions in subjects suffering from an Usher syndrome. More precisely, this gene therapy takes advantage of an AAV2/8 vector expressing at least one USH1 gene product, preferably SANS.

The present invention relates to a HSP27 mutation (S135F) mediated Charcot-Marie-Tooth disease (CMT) animal model. Particularly, the vector expressing mutant HSP27 protein wherein the 135.sup.th serine is substituted with phenylalanine has been injected in the mouse zygote and then the mouse harboring the expression vector was selected. The selected mouse was confirmed to display Charcot-Marie-Tooth disease phenotype, so that the animal model was expected to be efficiently used for the evaluation of the effect of Charcot-Marie-Tooth disease treating material candidates.

A genetically modified rodent is provided that comprises a modified Acvr1 gene that comprises a conditional altered exon 7 encoding R258G in antisense orientation, flanked by site-specific recombinase recognition sites, wherein the altered exon is inverted to sense orientation upon action of a recombinase, resulting in ectopic bone formation.