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.

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.

Proteins, compositions, and methods for treating Farber disease are provided.

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 a method of treating a disease or disorder associated with an abnormality in CNS function. Also provided is a method for diagnosing and/or identifying a subject having an abnormality in CNS function. FAM19A1 antagonists that can be used with the present disclosures are also provided.

The disclosure provides for methods and compositions for treating a premature aging disorder or neurodegenerative disorder, particularly neurodegenerative disorders associated with amyloid deposition and neuronal death, such as Alzheimer's disease. Accordingly, aspects of the disclosure relate to a method for treating a premature aging disorder in a subject in need thereof, comprising administering a TERT activating therapy to the subject. Further aspects relate to a method for treating a neurodegenerative disorder in a subject comprising administering a TERT activating therapy to the subject.

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.

Non-human animals, tissues, cells, and genetic material are provided that comprise a modification of an endogenous non-human heavy chain immunoglobulin sequence and that comprise an ADAM6 activity functional in a mouse, wherein the non-human animals express a human immunoglobulin heavy chain variable domain and a cognate human immunoglobulin λ light chain variable domain.

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.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) IL1B and/or IL1A, and methods of use thereof.