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

A method of producing a conditional knockout animal, and techniques related thereto, e.g., a method of efficiently producing a floxed animal, are provided. By introducing recombinase recognition sequences such as loxP into both ends of a target region on a chromosome at different timings, an animal having the pair of recombinase recognition sequences on the chromosome, such as a floxed animal, is produced.

A primatized rodent or swine, and methods of making and using the primatized rodent or swine, are provided.

The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems, wherein the guide sequence is modified by secondary structure to increase the specificity of the CRISPR-Cas system and whereby the secondary structure can protect against exonuclease activity and allow for 5′ additions to the guide sequence.

Disclosed herein are rodents (such as mice and rats) genetically modified at an endogenous Scn9a locus to comprise an exogenous Scn nucleotide sequence such as the coding sequence of a human SCN2A gene. Also disclosed are methods and compositions useful for making such rodents, and methods of using such rodents for generating anti-NaV1.7 antibodies.

A non-human mammalian model for human diseases or disorders comprising a non-human neutrophil depleted mammalian host engrafted with a human skin equivalent (huSE) and human immune cells.

Provided is use of thiamine pyrophosphokinase TPK as a target in the treatment of Alzheimer's disease; and AD symptoms due to the inhibited TPK can be prevented by promoting the kinase activity and/or expression level of TPK protein in brain with TPK as a target.

Provided are non-human animals, including humanized bone marrow/liver/thymus (BLT) non-human animals, that include a recipient immunodeficient animal with human thymus tissue and human liver tissue, both implanted under a kidney capsule of the recipient immunodeficient animal, and transplanted hematopoietic stem cells derived from a human liver tissue. Such non-human animals have human thymus tissue and human liver tissue that are autologous with the hematopoietic stem cells derived from the human liver tissue. Methods of making such BLT non-human animals are also provided. Also disclosed herein are human immune system non-human animals and methods of making the same.

Provided are non-human animals, including humanized bone marrow/liver/thymus (BLT) non-human animals, that include a recipient immunodeficient animal with human thymus tissue and human liver tissue, both implanted under a kidney capsule of the recipient immunodeficient animal, and transplanted hematopoietic stem cells derived from a human liver tissue. Such non-human animals have human thymus tissue and human liver tissue that are autologous with the hematopoietic stem cells derived from the human liver tissue. Methods of making such BLT non-human animals are also provided. Also disclosed herein are human immune system non-human animals and methods of making the same.

A preparation method of an anti-PD-1/PD-L1 monoclonal antibody (mAb)-induced autoimmune myocarditis model is provided, including: mediating a model with adeno-associated virus 9 (AAV9) to achieve the high expression of PDL1 in a myocardial tissue, and applying an anti-PD-1/PD-L1 mAb to the model with high PDL1 expression in the myocardial tissue for modeling. The present disclosure also provides use of an animal model prepared by the preparation method. The model prepared by the present disclosure truly simulates the pathogenesis and clinical course of autoimmune myocarditis in a patient administered with an anti-PD1/PD-L1 mAb, is close to a pathophysiological status of a clinical patient, has a high modeling rate, and can be dynamically monitored.