An objective of the present invention is to provide non-human animal models of cancer pathology, which mimic the hierarchical organization, cancer progression process, or biological property of human cancer tissues, and uses thereof. To achieve the objective described above, first, the present inventors transplanted cells of NOG-established cancer lines into NOG mice and morphologically observed the resulting tissue organization. As a result, the non-human animal models were demonstrated to exhibit pathologies (the hierarchical organization, cancer progression process, or biological properties of the cancer cells) similar to that of human cancer. Specifically, the present inventors succeeded in preparing non-human animal models exhibiting pathologies more similar to a human cancer, and cell culture systems using NOG-established cancer cell lines where the in vitro cell morphology is more similar to that of human cancer.

The invention provides compositions and methods useful for the treatment and prevention of conditions associated with short telomere length.

Methods are disclosed herein for producing human hepatocytes from human induced pluripotent stem cells. Also provided are transgenic rats for the expansion of human hepatocytes, such as those produced using the methods disclosed herein.

A method and system for the treatment of honey bees (Apis mellifera), bats, and butterflies protects them from various life threatening conditions, including Colony Collapse Disorder and in particular, provides honey bees with the ability to assimilate and degrade pesticides such as neonicotinoids and fipronil.

Described herein are transgenic mice for testing immunogenicity and protective efficacy of a wide variety of therapeutic agents and vaccines, determining allograft rejection, and developing monoclonal antibodies and generating hybridomas. Methods of generating a transgenic mouse is also described. Described herein are mouse models capable of expressing B cell, a T cell, a monocyte, a macrophage, a dendritic cell, a NK cell, a iNKT cell, an innate lymphoid cell, a microglia cell, a red blood cell, which can develop into a functional human immune system.

Complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide are provided. Compositions and methods for delivery of complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide to mammals for both research and therapeutic use are provided. Methods of treating or reducing one or more symptoms of type 2 diabetes, prediabetes and/or gestational diabetes are provided.

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.

Disclosed herein are antigenic peptide-MHC complexes, termed comPACT polypeptides and comPACT polynucleotides, and methods of producing such complexes. Also discloses herein are methods of producing libraries of comPACT polynucleotides and polypeptides, and their exemplary use in capturing cancer neoepitope-reactive T cells with high accuracy. Dual particle detection approaches for detection of neoantigen specific T cells with improved sensitivity and specificity are provided. Signal to noise ratio analysis of isolated T cells for detection of neoantigen-specific T cells with improved T cells is also provided.

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.

Polynucleotide constructs and multifunctional engineered natural killer (NK) cells expressing such constructs are provided for the treatment of cancer and, in particular, glioblastoma. The constructs are a fusion of a first binding domain that targets at least one cognate ligand on a target cell, a second binding domain specific for an adenosine producing cell surface protein of the target cell or an adenosine-intermediary producing cell surface protein of the target cell and a cleavable linker, and a third binding domain specific for a cancer-associated antigen. Pharmaceutical compositions of the engineered NK cells are also provided, as well as methods of treating glioblastoma using such pharmaceutical compositions alone and in addition to autophagy inhibitors.