Provided is a bispecific recombinant protein, comprising a high affinity tumor-targeting arm and a low affinity fusion protein blocking the interaction of CD47 with SIRPα. The antibody corresponding to the high affinity tumor-targeting arm does not bind to CD47, and its binding affinity to the target antigen on the tumor cell is at least 6 times as great as the binding affinity of monomer fusion protein homodimer corresponding to the low affinity fusion protein blocking the interaction of CD47 with SIRPα, to a CD47 on the tumor cell, wherein the low affinity fusion protein blocking the interaction of CD47 with SIRPα comprises a SIRPα extracellular truncation. Also provided are nucleic acid molecules encoding recombinant proteins and the use of the recombinant proteins and nucleic acid molecules in the manufacture of a medicament for treating tumors.

Provided herein are methods and compositions for dynamically controlling and targeting multiple immunosuppressive mechanisms in cancer. Some aspects provide cells engineered to produce multiple effector molecules, each of which modulates a different immunosuppressive mechanisms of a tumor, as well as methods of using the cells to treat cancer, such as ovarian, breast, or colon cancer.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) IL10R and/or a human or chimeric (e.g., humanized) IL10, and methods of use thereof.

The present disclosure provides methods and compositions for high frequency mouse transgenesis using, for example, a Bxb1 landing pad.

Disclosed herein are classifier models, computer implemented systems, machine learning systems and methods thereof for classifying clinical variants of unknown or uncertain significance into a pathogenicity category using measured phenotype features extracted from phenotype assays of transgenic organism expressing the human clinical variant. Embodiments of the present invention relate generally to methods for generating classifier models using machine learning and use of those classifier models to predict the pathogenicity of a clinical variant for a specific human disease (e.g. genetic disease), assigning a patient clinical variant to a pathogenicity category (e.g. pathogenic or benign) for the specific human disease to determine whether that patient should be followed up with additional, more invasive diagnostic testing, or treatment.

Genetically modified non-human animals comprising a humanized interleukin-15 (IL-15) gene. Cells, embryos, and non-human animals comprising a human IL-15 gene. Rodents that express humanized or human IL-15 protein.

Genetically modified mice and methods and compositions for making and using the same are provided, wherein the genetic modification comprises humanization of an FcγRI protein.

The present disclosure relates to the genetically modified non-human animals that express a human or chimeric OX40, and methods of use thereof.

This disclosure relates to genetically modified rodent animals and rodent models of human diseases. More specifically, this disclosure relates to genetically modified rodents whose genome comprises a humanized Il1rl2 gene (coding for the IL1rl2 subunit of the IL-36R protein) and human IL-36α, β and γ ligand genes. The genetically modified rodents disclosed herein display enhanced skin and intestinal inflammation as a preclinical model of psoriasis and IBD, respectively, and serve as a rodent model of human DITRA disease.

This disclosure relates to genetically modified immunodeficient animals which express a human or chimeric (e.g., humanized) SIRPα and/or human or chimeric (e.g., humanized) CD47, and methods of use thereof.