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.

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 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.

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

Disclosed herein are chimeric blastocysts, such as chimeric blastocysts derived from a host blastocyst from a first mammalian species and having donor pluripotent stem cells from a second mammalian species, wherein the donor pluripotent stem cells have reduced expression or reduced biological activity of one or more proteins in the TLR/NF-kB signaling pathway or the p53 pathway. Methods of preparing chimeric blastocysts and methods of obtaining mammalian organs and tissues are also provided.

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized albumin (ALB) 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 albumin locus express a human albumin protein or a chimeric albumin protein, fragments of which are from human albumin. Methods are provided for using such non-human animals comprising a humanized albumin locus to assess in vivo efficacy of human-albumin-targeting reagents such as nuclease agents designed to target human albumin.

Aspects of the disclosure relate to antibodies that bind to transferrin receptor (e.g., transferrin receptor 1) and complexes comprising the antibody covalently linked to a molecular payload. Methods of making and using the antibodies are also provided.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) IL2RA, and methods of use thereof.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD38, and methods of use thereof.