Provided are antibodies, and fragments, derivatives, and nanoparticle conjugates thereof, particularly humanized derivatives thereof, which bind to tumor antigens. Also provided are nucleic acid molecules encoding chimeric antigen receptors (CARs) that bind to tumor antigens, polypeptides and CARs encoded by the nucleic acid molecules, vectors and host cells that include the nucleic acid molecules, methods of making the same, and methods for using the same to generate a persisting population of genetically engineered T cells in a subject, expanding a population of genetically engineered T cells in a subject, modulating the amount of cytokine secreted by a T cell, reducing the amount of activation-induced calcium influx into a T cell, providing an anti-tumor immunity to a subject, treating a mammal having a MUC1-associated disease or disorder, stimulating a T cell-mediated immune response to a target cell population or tissue in a subject, and imaging a MUC1-associated tumor.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) LAG3, and methods of use thereof.

The present invention relates a vector system and a vector system for use in a method of treating a disease, each comprising a first vector and a second vector. The present invention further relates to the first vector, the second vector and a combination of the first vector and the second vector. In addition, the present invention relates to a pharmaceutical composition comprising the vector system of the invention or the combination of the invention.

Genetically modified non-human animals are provided that exhibit a functional lack of one or more lncRNAs. Methods and compositions for disrupting, deleting, and/or replacing lncRNA-encoding sequences are provided. Genetically modified mice that age prematurely are provided. Also provided are cells, tissues and embryos that are genetically modified to comprise a loss-of-function of one or more lncRNAs.

Methods and compositions are provided for activating transcription in a mammalian cell.

The present invention relates to a method of treating a tauopathy in a subject, a method of improving cognitive ability in a subject suffering from cognitive impairment associated with a tauopathy, a method of reducing tau aggregates and neurofibrillary tangles. The method comprises administering an agent which promotes phosphorylation of tau at threonine in the sequence SSPGSPGTPGSRSR of the tau; and/or introduces a phosphomimetic of a phosphorylated tau, wherein the phosphorylated tau is tau that has been phosphorylated at threonine in the sequence SSPGSPGTPGSRSR of the tau.

The present disclosure provides transgenic nematode systems for assessing function of heterologous genes, their variants and drug discovery. The transgenic nematodes contain a heterologous gene that is inserted via homologous recombination at the native locus replacing and removing the nematode ortholog, wherein expression of the heterologous gene rescues function of the removed nematode ortholog and a transgenic control animal is provided. The heterologous gene may be further modified to provide a variant, such as a human clinical variant, whereby a transgenic test animal is provided. Those transgenic test animals are used in methods to assess function of the heterologous variant and drug screens to find therapeutic candidates reversing deviant activity back to wildtype.

As disclosed herein, β-arrestin1 and β-arrestin2 levels are highly elevated in brains of FTLD-tau patients suggesting that both β-arrestin1 and β-arrestin2 are elevated in the brains of patients with AD and FLTD. The current work also shows that when β-arrestin2 is overexpressed, tau levels become elevated. The data indicate that β-arrestin2 reduces tau clearance by impairing p62-mediated autophagy, a role carried out by the oligomerized form of β-arrestin2. Therefore, disclosed herein are β-arrestin oligomerization inhibitors that can be used to prevent β-arrestin oligomerization and therefore the accumulation of tau in cells, i.e. tauopathy. Also disclosed are methods of treating a tauopathy in a subject that involve administering to the subject a therapeutically effective amount of a β-arrestin oligomerization inhibitor disclosed herein.

The present disclosure provides transgenic non-human animal (e.g., nematode) systems for assessing heterologous polygenic or monogenic phenotypes, their variants and drug discovery. The transgenic non-human animals (e.g., nematodes) contain a first heterologous polypeptide coding sequence and a second heterologous polypeptide coding sequence (a plurality of heterologous polypeptide coding sequences), wherein the first and second heterologous polypeptide coding sequences are integrated into the host animal genome, and wherein expression of the first and second heterologous polypeptide coding sequence contribute to the heterologous phenotype. The plurality of heterologous polypeptide coding sequences are interrelated wherein their expression products, directly or indirectly, contribute or lead to an observable phenotype.

The present invention relates, inter alia, to processes for making modified fish zygotes or early-stage fish embryos (particularly salmon zygotes and salmon embryos). The invention also provides fish zygotes, fish embryos, juvenile fish, mature fish and sterile fish which are produced by the processes of the invention.