The present invention provides a method of lowering blood pressure in a subject, comprising genetically modifying a myosin phosphatase target subunit (Mypt1) gene in a vascular smooth muscle cell of the subject, whereby the genetic modification of Mypt1 results in a deletion or inactivation of exon 24. The invention further provides vectors, host cells, and compositions useful for carrying out the methods of the invention.

The present invention provides a kidney production method including a step of tissue-specifically removing a metanephric mesenchyme of a metanephros of a non-human animal; a step of transplanting a human kidney precursor cell into the metanephros; and a step of advancing development of the metanephros, which is a step in which the transplanted human kidney precursor cell is differentiated and matured to form a part of the kidney.

Embodiments of the present invention provide methods for the treatment or prevention of infection-related immune conditions using compositions comprising IgM.

Described herein are donor vectors and systems for use in in vivo dual recombinase-mediated cassette exchange. Also described are animal models for consistent, rigorous, and facile investigation of transgene expression. Further described are methods of screening for therapeutic drugs using these animal models, and methods of treatment.

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

Methods, uses, and animals for introgression of alleles between animals, including SNPs. One embodiment involves introducing a targeted targeting endonuclease system and a HDR template into a cell with a mismatch in the binding of the targeting endonuclease and the targeted site.

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 relates to genetically modified non-human animals (e.g., genetically-modified mice or rodents) that express a hACE2 and/or hTMPRRS2 under control of the mouse promoter and the genetically modified non-human animal does not express native ACE2 and/or hTMPRRS2. The present disclosure also relates to methods of generating the genetically-modified animals (e.g., genetically modified mice or rodents), and methods of using the genetically modified non-human animals (e.g., genetically modified mice or rodents) described herein.

A transgenic non-human animal is provided. In certain embodiments, the animal comprises a genome comprising an immunoglobulin heavy chain locus comprising: a) a transcribed gene encoding a fusion protein comprising, from N-terminus to C-terminus: i. a scaffold comprising a first binding domain; and ii. a heavy chain constant region operably linked to the scaffold; wherein the scaffold is capable of specifically binding to a target in the absence of additional polypeptides; and b) a plurality of pseudogenes that are operably linked to the transcribed gene and that donate, by gene conversion, nucleotide sequence to the part of the transcribed gene that encodes the binding domain.

The present invention relates to a preparation method for an animal model with Alzheimer's disease by injecting a human mutant tau (AAV-hTau) vector and adenovirus into an animal. The preparation method for an AD animal model provided by the present invention may contribute to the development of the field of treatment technology for treating AD since the preparation method causes AD pathology to appear as early as 8 months old and facilitates studies on AD target treatment strategies and tau pathology.