Proteins, compositions, and methods for treating Farber disease are provided.

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.

Aspects of the disclosure relate to antibodies that bind to transferrin receptor (e.g., transferrin receptor 1) and complexes comprising the antibody covalently linked to a molecular payload. Methods of making and using the antibodies are also provided.

The present invention is directed to improved AAV gene therapy constructs and pharmaceutical compositions for the expression of Kir7.1. The gene therapy constructs are particularly AAV vector comprising a promoter operably connected to a polynucleotide encoding a Kir7.1 polypeptide which is capable of being expressed in retinal pigment epithelium cells. Methods of treating a subject having a condition associated with insufficient expression or function of a Kir7.1 polypeptide are also provided.

Described herein are compositions comprising viral vectors. The viral vectors may encode a t-tubule organizing protein or peptide such as cardiac isoform of bridging integrator 1 (cBIN1). Also disclosed herein are methods for treatment or prophylaxis of heart failure in a subject in need thereof. The method of treatment or prophylaxis may include administering a vector comprising cBIN1 to the subject for rehabilitating or increasing contractile (systolic) function or relaxation (diastolic) function in the heart of a subject having experienced heart failure or having chronic myocardial stress.

In some aspects the disclosure provides compositions and methods for promoting expression of functional Forkhead box G1 (FOXG1) protein in a subject. In some embodiments, the disclosure provides methods of treating a subject having FOXG1 deficiency.

This invention relates to viral vectors for delivery of α-N-acetylglucosaminidase (NAGLU) to a subject. In some aspects the NAGLU sequence is optimized for expression in human cells. The invention further relates to methods of using the vector to increase secretion of NAGLU from a cell and for treatment and prevention of mucopolysaccharidosis IIIB.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD38, and methods of use thereof.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

The invention relates to the use of vectors to improve vision by restoring RPE phagocytosis of photoreceptor outer segments in a patient suffering from retinal dysfunction and/or degeneration.