Provided herein are methods and compositions related to the in vivo testing of therapeutic agents comprising a human Fc in genetically modified rodents (e.g., the testing of the pharmacokinetic and/or pharmacodynamic properties of such a therapeutic agent in genetically modified rodents). In some embodiments the genetically modified rodents express antibodies comprising a human Fc (e.g., a human IgG1 Fc, a human IgG4 Fc). In some embodiments, the rodents express fully human antibodies (i.e., antibodies having human heavy chains and human light (γ or κ) chains). In certain embodiments the genetically modified rodents comprise one or more Fc receptors with a human extracellular domain (e.g., a Neonatal Fc Receptor (FcRn), a β-2-microglobulin polypeptide (β2M), a Fc ε receptor 1α (FcεR1α), a Fc γ receptor 1 alpha (FcγR1a), a Fc gamma receptor 2a (FcγR2a), a Fc gamma receptor 2b (FcγR2b), a Fc gamma receptor 3a (FcγR3a), a Fc gamma receptor 3b (FcγR3b), a Fc gamma receptor 2c (FcγR2c)). The transmembrane and cytoplasmic domain of such receptors can be human or non-human (e.g., rodent).

The disclosure in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the disclosure relates to gene transfer methods using the recombinant adeno-associated viruses. In some aspects, the disclosure relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.

Provided in the present invention is a chicken whole-genome SNP chip and application thereof. There are a total of 50,000 SNP loci on the chip: including 19,600 SNP loci for white-feather broilers, yellow-feather and partridge chickens having a MAF value greater than 0.05 and uniformly distributed across the genome which were derived from the data of the whole-genome resequencing of main indigenous chicken breeds in China and introduced chicken breeds; 14,000 SNP loci associated with economic traits, and 16,400 SNP loci for making up for the genomic regions that are not covered by the first two types of probes. The 50,000 SNP loci on the chicken whole-genome SNP chip of the present invention have DNA sequences represented by SEQ ID NOs. 1 to 50,000. The SNP loci on the chip are uniformly distributed across the whole genome, and associated with traits such as feed efficiency, meat production rate, lipid metabolism, meat quality, general resistance to diseases, reproduction and the like, and the chip has moderate through-put and low cost, and could be used universally for chicken breeds at indigenous and abroad.

Genetically modified non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome are provided. Also provided are methods for making non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome, and methods for using non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human T cell and/or natural killer (NK) cell development and function, in modeling human pathogen infection of human T cells and/or NK cells, and in various in vivo screens.

The current disclosure has identified novel developmental, cellular, molecular, and biochemical pathways and developed a unique mouse model which recapitulates age, bicuspid aortic valve-associated, and gender-specific pathological aspects of development and progression of human CAVD, which will be useful in developing novel diagnostic, preventative, and therapeutic strategies for CAVD patients.

The disclosure provides a method for producing hepatocytes or hepatic progenitor cells; a method for suppressing hepatocyte aging using a drug causing histone hyperacetylation; a hepatocyte anti-aging agent; a method for increasing hepatocyte plasticity; and a drug for increasing hepatocyte plasticity.

Models and methods related to targeting binding immunoglobulin protein (BiP) are described, where the models and methods allow identification and analysis of protein folding and misfolding.

Therapeutic methods and medicines may be developed by identifying a gene responsible for progressive supranuclear palsy, as may effective therapeutic methods and medicines. A medicine for progressive supranuclear palsy may contain a compound for inhibiting the expression of a filamin-A gene is provided. Also provided is an assessment system that uses cells expressing filamin-A, which is used in the search for medicaments for progressive supranuclear palsy or their candidates.

The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a SIN CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing SIN CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Single nucleotide polymorphic sites of the bovine MAP1B, PPP1R11, and DDX4 genes are associated with improved bull fertility as measured by e.g. sire conception rates. Nucleic acid molecules, arrays, kits, methods of genotyping and marker-assisted bovine breeding methods based on these SNPs are disclosed.