Tandem gene pairs are described in which the GC3 Content of one gene changes its level of expression, and changes the level of expression of the tandem gene. This gene control is called Mercury and can be used to control the expression level of a gene of interest. Mercury is used herein to reduce tonic signaling from chimeric antigen receptors by reducing the expression of a chimeric antigen receptor.

The application relates to the use of loaded red blood cells (e.g. “RBCs”, “red cells” or “erythrocytes”) or red blood cell precursors to produce red cell extracellular vesicles (RCEVs) containing cargos, including cargos comprising biologically active ingredients. Notable red cell precursors include hematopoietic stem cells (HSCs), induced pluripotent stem cells (iPSCs), and reticulocytes. The cargo may comprise nucleic acids, proteins, small molecules, or components of a gene editing system, including CRISPR/Cas9. The RCEVs may be used to treat of diseases and disorders including autoimmune disorders, cancers, cardiovascular diseases, gastrointestinal diseases, genetic disorders, or inflammatory diseases. The RCEVs may also be used to carry antigens and or immune modulator, for use in eliciting immune or immune tolerance responses. Also provided are methods for producing cargo loaded RCEVs (CLRCEVs) by first loading cargo into red cells and then by vesiculating the cargo loaded red cells to yield the CLRCEVs.

The present disclosure relates to genetically modified non-human animals that express a fusion protein including B2M and FcRn, and methods of use thereof. In some embodiments, the animals can have a B-NDG background. In some embodiments, the endogenous B2M gene is knocked out in the animals.

Methods of generating spinal cord glutamatergic interneurons (V2a interneurons) from human pluripotent stem cells (hPSCs) are provided. A method of the present disclosure may include culturing a first population of hPSCs in vitro in a neural induction medium that includes: a retinoic acid signaling pathway activator; a sonic hedgehog (Shh) signaling pathway activator; and a Notch signaling pathway inhibitor, wherein the culturing results in generation of a second population of cultured cells containing CHX10+ V2a interneurons. Also provided are non-human animal models that include the hPSC-derived spinal cord glutamatergic interneurons, and methods of producing the non-human animal models.

In order to develop tools and methods useful in a variety of applications, including the research and development of medical treatments which involve the modification of collagen protein and use of the same, the present invention provides a modified collagen protein expressed in a transformed cell and capable of forming collagen fibers outside of the cell, wherein the transformation is performed by introducing, into the cell, polynucleotides coding the modified collagen protein.

The present invention relates to a system for screening personalized anticancer agents, a method for screening personalized anticancer agents using the system, and an apparatus for screening personalized anticancer agents. When the inventive system for screening personalized anticancer agents is used, an anticancer agent showing an optimal anticancer activity against cancer cells collected from a patient can be selected from a variety of anticancer agents, and it is possible to previously examine a therapeutic response that can appear when the selected anticancer agent is administered into the patient. Thus, the risk of trial and error in cancer therapy can be reduced, and the cost and time required for cancer therapy can be reduced.

Residual, refractory or relapsed cancer is treated by immunostimulation in the presence of allogeneic immune effector cells, optimally in combination with radiation therapy. The methods of the disclosure induce a systemic allogeneic anti-tumor immune response that results in tumor regression in untreated sites of disease, i.e. non-injected, non-irradiated, etc.

Provided herein is a method for treating and/or preventing various diseases including a decrease in glucose tolerance and a decrease in cognitive ability associated with aging with adipocytes over-expressing FFAR4 and a transplant composition including the adipocytes.

The present application provides peripheral blood mononuclear cells comprising an antigen, methods of manufacturing such PBMCs, and methods of using such PBMCs, such as for modulating an immune response in an individual. In some embodiments, the PBMCs are conditioned by incubating the PBMC in the presence of an adjuvant.

The present disclosure relates to genetically modified non-human animals expressing human or chimeric (e.g., humanized) Thrombopoietin (THPO), and methods of use thereof.