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.

A therapeutic regimen useful for treatment of GM1 gangliosidosis comprising administration of a recombinant adeno-associated virus (rAAV) vector having an AAV capsid and a vector genome comprising a sequence encoding human β-galactosidase is provided. Also provided are compositions containing a rAAV vector and methods of treating GM1 gangliosidosis in patient comprising administration of a rAAV vector.

Disclosed are methods and compositions related to methods of treating, ameliorating, mitigating, slowing, arresting, preventing or reversing various diseases and conditions, including age-related obesity, age-related increases in blood lipid levels, age-related decreases in insulin sensitivity, age-related decreases in memory function, and age-related changes in eye function such as macular degeneration. The methods comprise administering nicotinamide mononucleotide (NMN) to a subject. In some embodiments, the administration can be oral administration. Also disclosed are pharmaceutical compositions comprising NMN.

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.

Among the various aspects of the present disclosure is the provision of engineered cells, animal models, and uses thereof for modeling low grade glioma (LGG). An aspect of the present disclosure provides for a population of cells engineered to silence, downregulate, knock out, or reduce or knock down Cxcl10 expression. Another aspect of the present disclosure provides for an animal engineered to be deficient in Cxcl10, downregulate or reduce expression of Cxcl10, knock out Cxcl10, or knock down Cxcl10 (e.g., Cxcl10.sup.−/− mice). Yet another aspect of the present disclosure provides for a method of growing tumor cell lines or patient-derived xenografts for LGG tumors in an animal (e.g., mouse, rat) including providing a mouse or rat harboring somatic homozygous deletion in the Rag1 or Cxcl10 gene, and implanting an amount of the cells in mice sufficient to grow a tumor.

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 provides a composite comprising a novel antibody and at least one selected from the group consisting of a solid phase support and a labeled substance. The antibody consists of the amino acid sequence represented by SEQ ID NO: 08, and is capable of binding to an intranuclear protein of an influenza virus type A. The influenza virus type A is at least one selected from the group consisting of H1N1, H2N2, H3N2, and H7N9. The antibody is bound to the at least one selected from the group consisting of a solid phase support. The present invention also provides a detection device and a detection method using the composite.

Methods of generating functional human organs and tissue in animal bodies suitable for transplantation into human subjects are provided. In particular, the contribution of human donor cells to tissues and organs can be increased in interspecies host embryos by knocking out a growth factor receptor gene such as the insulin-like growth factor 1 receptor or insulin receptor gene. Almost entirely donor-derived functional organs and tissue can be generated by using this method. The methods described herein are useful for generating human organs and tissue in animals and may be helpful for overcoming the current problems with organ shortage for transplantation therapy. Additionally, such organs and tissue can be used in drug discovery, drug screening, and toxicology testing.

The present disclosure provides AAV8 vectors and variants thereof that express nucleic acids sharing identity to a codon optimized NAGLU (coNAGLU) that improves transduction and distribution in brain cells and will improve disease outcomes in the Mucopolysaccharidoses IIIB (MPS IIIB) mouse model. The present disclosure also provides methods of treatment of a subject, and methods of transducing one or more brain cells, by administering these vectors, as well as uses of these vectors in the manufacture of medicaments for treatment. The present disclosure also provides compositions and host cells comprising rAAV vectors and rAAV particles that express a coNAGLU heterologous nucleic acid and confer enhanced transduction efficiency in human cells, such as brain cells (e.g., neurons). These compositions may be administered to a subject in need thereof.

Described herein is a method for producing a chimeric non-human animal expressing a human ETV2 gene comprising: a) generating an ETV2 null non-human animal cell, wherein both copies of the non-human ETV2 gene carry a mutation that prevents production of functional ETV2 protein in said non-human animal; b) creating an ETV2 null non-human blastocyst by somatic cell nuclear transfer comprising fusing a nucleus from said ETV2 null non-human animal cell of a) into an enucleated non-human oocyte and activating said oocyte to divide so as to form an ETV2 null non-human blastocyst; c) introducing human stem cells into the ETV2 null non-human blastocyst of b); and d) implanting said blastocyst from c) into a pseudopregnant surrogate non-human animal to generate a chimeric non-human animal expressing human ETV2.