Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.

The present invention relates to synthetic retinal ON-bipolar cell-specific promoter sequences and their use in therapeutic transgene delivery to the eye for the improvement and/or restoration of vision. The invention features metabotropic glutamate receptor 6 (mGluR6) promoters for an increased and more specific expression in ON-bipolar cells, in particular in cone ON-bipolar cells of the human macula.

The present disclosure relates to compositions and methods useful for treating glycogen storage disorders, such as type II glycogen storage disorder, also referred to herein as Pompe disease. Using the compositions and methods of the disclosure, a patient (e.g., a mammalian patient, such as a human patient) having Pompe disease may be administered a viral vector, such as an adeno-associated viral (AAV) vector, that contains a transgene encoding acid alpha-glucosidase.

Provided herein are nucleic acid sequence encoding hIDUA and expression cassettes containing these coding sequences. Also provided are vectors, such as recombinant adeno-associated virus (rAAV) vectors having a vector genome including a hIDUA coding sequence operably linked regulatory sequences that direct expression of the hIDUA. Also provided are compositions containing these expression cassettes and rAAV vectors and methods of treating MPS1 or an associated syndrome such as Hurler, Hurler-Scheie and/or Scheie syndrome. The compositions and methods provided are further designed to selectively repress expression of hIDUA in dorsal root ganglia.

The present invention relates to a technique for effective intranasal delivery to the brain. More specifically, the present invention is used for diagnosing, preventing or treating central nervous system encephalopathy, neurodegenerative diseases or brain tumor by effectively delivering to the brain a pH-responsive and bioreducible PPA polymer, which can be used as a drug carrier, by means of nasal administration.

The present disclosure relates to AAV gene therapy vectors, AAV replicons, and pharmaceutical compositions for delivering a human HDAC8 gene to a subject for treating Cornelia de Lange Syndrome. In addition, methods of treatment and gene transfer are provided.

The present invention relates to polynucleotides comprising a Factor IX nucleotide sequence, wherein the Factor IX nucleotide sequence comprises a coding sequence that encodes a Factor IX protein or fragment thereof and wherein a portion of the coding sequence is not wild type. The present invention further relates to viral particles comprising a recombinant genome comprising the polynucleotide of the invention, compositions comprising the polynucleotides or viral particles, and methods and uses of the polynucleotides, viral particles or compositions.

Methods for introducing a gene into a cell of the inner ear, e.g., a cochlear or vestibular cell, e.g., a hair cell, e.g., for therapy, that include the use of exosomes associated with one or more adeno-associated viral (AAV) particles.

The present invention relates to the field of recombinant viral vectors suitable for the delivery of therapeutic genes in vivo. Described is an adeno-associated virus (AAV) vector comprising (i) a human growth hormone intron 3 (hGHi3) sequence (ii) a synapsin promoter sequence and/or (iii) a progranulin 3′ untranslated region (UTR) sequence, operably coupled to a polynucleotide sequence encoding a polypeptide of interest. Specific use of such a vector lies in the enhanced expression of a polypeptide of interest, such as progranulin (PGRN), to treat subjects who have a genetic mutation or intrinsic polypeptide level that is below a physiologically normal level.

The present disclosure relates to methods of targeting specific cell types within the cochlea using optimized gene therapy vectors. In particular, the disclosure provides gene therapy vectors to specifically target cochlear cells and methods of treating hearing impairment and hearing-loss related disorders.