Abstract: Rat cells and rats comprising an inactivated Cfh locus and methods of making and using such rat cells and rats are provided. The rats comprising an inactivated Cfh locus model C3 glomerulopathy (C3G). Methods are provided for using such rats comprising an inactivated Cfh locus to assess in vivo efficacy of putative C3G therapeutic agents.

Abstract: Methods of reducing the risk of venous thromboembolism (VTE) in a subject undergoing anticoagulant treatment by selectively depleting Factor V Leiden (FVL) in a subject that is heterozygous for FVL, or replacing FVL in the genome of a subject that is homozygous for FVL with a functional Factor V gene, and methods of identifying a subject undergoing anticoagulant treatment who is at risk of developing VTE are disclosed herein.

Abstract: 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.

Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized coagulation factor XII (F12) 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 F12 locus express a human coagulation factor XII protein or a chimeric coagulation factor XII protein, fragments of which are from human coagulation factor XII. Methods are provided for using such non-human animals comprising a humanized F12 locus to assess in vivo efficacy of human-coagulation-factor-XII-targeting reagents such as nuclease agents designed to target human F12. A short isoform of F12 that is produced locally in the brain, and methods of using the short isoform, are also provide.

Abstract: Guide RNAs and CRISPR/Cas systems targeting a C5 locus or gene, lipid nanoparticles or viral vectors comprising such guide RNAs or CRISPR/Cas systems, and cells or animals comprising such guide RNAs or systems are provided. Methods of modifying or knocking down or knocking out a C5 locus or gene using the CRISPR/Cas systems are also provided, as well as use of the CRISPR/Cas systems in prophylactic and therapeutic applications for treatment and/or prevention of a disease, disorder, or condition associated with C5 and/or for ameliorating at least one symptom associated with such disease, disorder, or condition.

Abstract: The present disclosure provides methods of treating a subject having a kidney disease or preventing a subject from developing a kidney disease by administering an Angiopoietin Like 3 (ANGPTL3) inhibitor and a Solute Carrier Family 5 Member 2 (SLC5A2) inhibitor, and methods of identifying subjects having an increased risk of developing a kidney disease.

Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized coagulation factor XII (F12) 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 F12 locus express a human coagulation factor XII protein or a chimeric coagulation factor XII protein, fragments of which are from human coagulation factor XII. Methods are provided for using such non-human animals comprising a humanized F12 locus to assess in vivo efficacy of human-coagulation-factor-XII-targeting reagents such as nuclease agents designed to target human F12. A short isoform of F12 that is produced locally in the brain, and methods of using the short isoform, are also provide.

Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized coagulation factor XII (F12) 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 F12 locus express a human coagulation factor XII protein or a chimeric coagulation factor XII protein, fragments of which are from human coagulation factor XII. Methods are provided for using such non-human animals comprising a humanized F12 locus to assess in vivo efficacy of human-coagulation-factor-XII-targeting reagents such as nuclease agents designed to target human F12. A short isoform of F12 that is produced locally in the brain, and methods of using the short isoform, are also provide.

Abstract: The present disclosure provides monoclonal antibodies that bind to the natriuretic peptide receptor 1 (NPR1) protein, and methods of use thereof. In various embodiments of the disclosure, the antibodies are fully human antagonist antibodies that bind to NPR1. In some embodiments, the antibodies of the disclosure are useful for blocking NPR1 signaling and/or activity, thus providing a means of treating or preventing a disease, disorder, or condition associated with NPR1, including hypotension, in humans.

Abstract: 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.

Abstract: The present disclosure provides methods of treating a subject having a kidney disease or at risk of developing a kidney disease by administering an Angiopoietin Like 3 (ANGPTL3) inhibitor, and methods of identifying subjects having an increased risk of developing a kidney disease.

Abstract: 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.

Abstract: The present invention provides monoclonal antibodies that bind to the natriuretic peptide receptor 1 (NPR1) protein, and methods of use thereof. In various embodiments of the invention, the antibodies are fully human antibodies that bind to NPR1. In some embodiments, the antibodies of the invention are useful for activating NPR1 activity, thus providing a means of treating or preventing a disease, disorder or condition associated with NPR1 in humans.

Abstract: The present disclosure provides novel immunoglobulin proteins that bind to a human natriuretic peptide receptor 1 (NPR1) agonist, preferably an anti-NPR1 antibody. In certain embodiments, the proteins of the disclosure comprise at least one immunoglobulin variable domain that binds to an anti-NPR1 antibody. In certain embodiments, the proteins of the disclosure are useful in blocking and/or reversing the effect of an administered anti-NPR1 antibody. In certain embodiments, the antigen-binding proteins are useful for effective management of blood pressure and hemodynamics in humans.

Abstract: The present invention provides monoclonal antibodies that bind to the natriuretic peptide receptor 1 (NPR1) protein, and methods of use thereof. In various embodiments of the invention, the antibodies are fully human antibodies that bind to NPR1. In some embodiments, the antibodies of the invention are useful for activating NPR1 activity, thus providing a means of treating or preventing a disease, disorder or condition associated with NPR1 in humans.

Abstract: Rat cells and rats comprising an inactivated Cfh locus and methods of making and using such rat cells and rats are provided. The rats comprising an inactivated Cfh locus model C3 glomerulopathy (C3G). Methods are provided for using such rats comprising an inactivated Cfh locus to assess in vivo efficacy of putative C3G therapeutic agents.

Abstract: The present invention provides methods for preventing and treating cardiac dysfunction, including cardiomyopathy and heart failure. The methods of the invention feature the administration of an antagonist of Activin A, e.g., a therapeutically effective amount of an antibody that binds to and reduces or neutralizes the activity of human Activin A. The methods of the invention are useful in preventing and treating cardiac disease from multiple causes, including viral disease, e.g., COVID-19.

Abstract: 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.

Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized coagulation factor XII (F12) 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 F12 locus express a human coagulation factor XII protein or a chimeric coagulation factor XII protein, fragments of which are from human coagulation factor XII. Methods are provided for using such non-human animals comprising a humanized F12 locus to assess in vivo efficacy of human-coagulation-factor-XII-targeting reagents such as nuclease agents designed to target human F12. A short isoform of F12 that is produced locally in the brain, and methods of using the short isoform, are also provide.

Abstract: Provided herein, inter alia, are non-human animals comprising nucleic acid sequences encoding a C3 protein that comprises a human sequence as well as transgenic non-human animals comprising a C3 gene that is human in whole or in part as well as methods for using the same to screen for candidate therapeutic molecules to treat complement-related nephropathies. Also provided herein are methods for improving kidney function in an individual diagnosed with or thought to have a complement-related nephropathy.