The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD40, and methods of use thereof.

In some aspects, the present invention provides chimeric transferrin receptor (TfR) polynucleotides and polypeptides. In other aspects, this invention provides chimeric TfR transgenic animal models and methods of using the animal models to identify therapeutics that can cross the blood-brain barrier.

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 disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) TNFR2, and methods of use thereof.

Provided are a donor vector having an exon-humanized gene in which only exon nucleotide sequences of a mouse gene are replaced with human exon nucleotide sequences, an ES cell in which a mouse endogenous gene is replaced with the donor vector, and a mouse crated by using the ES cell.

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized KLKB1 locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized KLKB1 locus express a human plasma kallikrein protein or a chimeric plasma kallikrein protein, fragments of which are from human plasma kallikrein. Methods are provided for using such non-human animals comprising a humanized KLKB1 locus to assess in vivo efficacy of human-KLKB 1-targeting reagents such as nuclease agents designed to target human KLKB1.

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.

Non-human animal cells and non-human animals comprising CRISPR/Cas synergistic activation mediator system components and methods of making and using such non-human animal cells and non-human animals are provided. Methods are provided for using such non-human animals to increase expression of target genes in vivo and to assess CRISPR/Cas synergistic activation mediator systems for the ability to increase expression of target genes in vivo.

The present invention relates to methods for increasing the diversity of monoclonal antibodies produced against an antigen. The methods of the invention utilize immunization of a murine host defective in one or more enzymes involved in a post-translational modification of a polypeptide or a modification of a lipid, wherein said modification is exposed on a cell surface. The invention also relates to monoclonal antibodies produced by these methods and which are not produced when a normal mouse is immunized with the same antigen. The invention further relates to compositions comprising these monoclonal antibodies, as well as to such monoclonal antibodies bound or conjugated to a toxin, a detectable marker or to a solid support.

A pharmaceutical composition contains Nkx3.2 and a fragment thereof as an active ingredient. The Nkx3.2 and/or the fragment thereof inhibit(s) retinal degeneration caused by oxidative stress and preserve(s) visual function. In addition, the Nkx3.2 and/or the fragment thereof inhibit(s) cell death due to the oxidative stress of retinal pigment epithelial cells and inhibit(s) choroidal neovascularization and retinal edema. Therefore, a composition containing the Nkx3.2 and/or the fragment thereof as active ingredient(s) can be effectively used for preventing or treating retinal dystrophies or macular degeneration.