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.

Provided herein are p-GlcNAc nanoparticle/nucleic acid compositions. In one aspect, the p-GlcNAc nanoparticle/nucleic acid compositions comprise deacetylated poly-N-acetylglucosamine lactate derivative nanoparticles less than 500 nm and a nucleic acid. Also, provided herein are methods for administering a nucleic acid to a subject, the method comprising administering to the subject a p-GlcNAc nanoparticle/nucleic acid composition. In certain embodiments, the p-GlcNAc nanoparti-cle/nucleic acid composition is administered subcutaneously to the subject.

This invention provides compositions and methods for preventing inflammatory diseases of the joints, including rheumatoid and osteoarthritis, tendonitis, bursitis, inflammation of the ligament, synovitis, gout, and systemic lupus erythematosus, wherein the methods include injecting into the inflamed joint a therapeutic anti-inflammatory composition comprising a bacterial or viral IL-10 expression construct, wherein the IL-10 expression construct comprises a bacterial or viral backbone and a nucleic acid sequence encoding interleukin-10.

The invention relates to improvements in drug delivery and more particularly to the use of Cell Penetrating Agents (CPA's) or Cell Penetrating Peptides (CPP's) which have been stabilized by, for example: i) stapling two amino acids to form Stapled CPP's (StaP's) or ii) stitching three or more amino acids to form stitched CPP's (StiP's). These stabilized CPP's are conjugated to a drug or Biologically Active Compound (BAC) directly or via a Bi-Functional Linker (BFL) so that the BAC can be carried though a cell membrane by the CPP. The resulting molecules are referred to as Drug Carrying Cell Penetrating Molecules (DCCPM's). The preferred BAC is an electrically low charge carrying oligonucleotide such as a phosphorodiamidate morpholino oligonucleotide (PMO). The invention also relates to a method of facilitating the uptake of a BAC into a cell, the use of a DCCPM in the treatment of a disease requiring alteration of an endogenous or exogenous gene, a method of improving the bioavailability of a drug or BAC, a method of introducing a drug or BAC to a site which is refractory to the drug or BAC in its native state, a method of treating a subject comprising administering the DCCPM's of the invention and to a pharmaceutical composition comprising the DCCPM and one or more pharmaceutically acceptable excipients.

Provided herein are methods, systems, and related vectors and compositions allowing for noninvasive control of neural circuits. In particular, the methods and systems herein described utilize acoustically targeted chemogenetics to achieve a noninvasive neuromodulation in specifically selected cell-types among spatially selected brain regions.

The present disclosure provides codon optimized nucleotide sequences encoding human REP1, vectors, and host cells comprising codon optimized REP1 sequences, and methods of treating retinal disorders such as choroideremia comprising administering to the subject a codon optimized sequence encoding human REP1.

The disclosure relates to pharmaceutical compositions comprising an adenoviral-based biological delivery and expression system encoding human or mammalian interleukin-1 receptor antagonist (IL-1Ra) and methods of using the pharmaceutical compositions for expressing IL-IRA in cells of one or more intervertebral discs of a subject suffering from degenerative disc disease (DDD) or a condition associated with DDD, and for treatment of DDD or conditions associated with DDD.

Disclosed are methods for treating or limiting development of diabetes, by transplanting into the eye of a subject with diabetes or at risk of diabetes an amount effective to treat or limit development of diabetes of insulin-producing cells engineered to reduce expression of a β3 subunit of Cav (Cavβ3).

Methods for treating bestrophinopathies are provided herein. The method includes, administering to an eye of the subject a dose of a recombinant adeno-associated virus (rAAV) vector comprising a nucleic acid sequence encoding a human BEST1 protein, wherein the subject has two mutant BEST1 alleles. Also provided are methods for evaluating treatments for retinal degeneration.

The present invention generally pertains to methods of treating X-linked juvenile retinoschisis and animal models thereof. In particular, the present invention pertains to the use of RS1 gene supplementation therapy by subretinal administration to treat X-linked juvenile retinoschisis and models thereof caused by one or more missense mutations of the RS1 gene.