The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) IL4R and/or IL4, and methods of use thereof.

Described herein are compositions, systems, and methods for treating, inhibiting, or ameliorating X-linked hyper IgM syndrome (X-HIGM) in subjects that have been identified or selected as being ones that would benefit from a therapy to treat, inhibit, or ameliorate X-HIGM. The systems include nuclease and vector donor constructs configured for co-delivery to modify endogenous CD40LG locus.

Disclosed are AAV viral-based vector compositions useful in delivering a variety of nucleic acid segments, including those encoding therapeutic polypeptides to selected mammalian host cells for use in therapeutic autoimmune modalities, including, for example, the in vivo induction of immunological tolerance via a liver-directed AAV-based gene therapeutic regimen for treating and/or ameliorating autoimmune disorders such as multiple sclerosis. Further disclosed are nucleic acid segments encoding therapeutic polypeptides that have been codon-optimized for expression in human cells.

The object of the present invention is to provide a test method using a novel administration method of an extract from inflamed tissues inoculated with vaccinia virus or a preparation containing the extract. It has been demonstrated that by sustainedly administering an extract from inflamed tissues inoculated with vaccinia virus or a preparation containing the extract by using a continuous administration device according to the present invention, a comparable effect is exerted at a very low dose compared with conventional administration methods such as oral administration. Therefore, the present invention can provide a test method using animals requiring less burden on a researcher, a treatment of patient at a low dose, and the like.

Disclosed herein are conditioning regimens and methods for inducing MHC- or HLA-mismatched mixed chimerism by conditioning a recipient with radiation-free, low-doses of cyclophosphamide (CY), pentostatin (PT), and anti-thymocyte globulin (ATG) prior to transplantation of donor bone marrow cells. In certain embodiments, the donor bone marrow cells may be CD4+ T-depleted bone marrow cells. The conditioning regimens and methods may also include administering one or more populations of conditioning donor cells selected from donor CD4.sup.+ T-depleted spleen cells, donor CD8.sup.+ T cells, and donor G-CSF-mobilized peripheral blood mononuclear cells. The conditioning regimen is clinically acceptable and can be used for treating hereditary hematological diseases and autoimmune diseases, as well as for promoting organ transplantation immune tolerance.

In one aspect, the invention provides methods of inhibiting the effects of MASP-2-dependent complement activation in a human subject suffering from graft-versus-host disease and/or diffuse alveolar hemorrhage and/or veno-occlusive disease associated with a hematopoietic stem cell transplant. The methods comprise the step of administering, to a subject in need thereof, an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD3e (T-cell surface glycoprotein CD3 epsilon chain), and methods of use thereof.

The present invention provides ungulate animals, tissue and organs as well as cells and cell lines derived from such animals, tissue and organs, which lack expression of functional endogenous immunoglobulin loci. The present invention also provides ungulate animals, tissue and organs as well as cells and cell lines derived from such animals, tissue and organs, which express xenogenous, such as human, immunoglobulin loci. The present invention further provides ungulate, such as porcine genomic DNA sequence of porcine heavy and light chain immunogobulins. Such animals, tissues, organs and cells can be used in research and medical therapy. In addition, methods are provided to prepare such animals, organs, tissues, and cells.

Genetically modified non-human animals and methods and compositions for making and using the same are provided, wherein the genetic modification comprises a humanization of an endogenous signal-regulatory protein gene, in particular a humanization of a SIRPα gene. Genetically modified mice are described, including mice that express a human or humanized SIRPα protein from an endogenous SIRPα locus.

The present disclosure relates to a method for preparing a Graves' ophthalmopathy phenotype animal model, the method including a step of administering zymosan A to a subject other than humans, a Graves' ophthalmopathy phenotype animal model prepared thereby, and a method for screening a therapeutic material for alleviation or treatment of Graves' ophthalmopathy. By using the method for preparing a Graves' ophthalmopathy phenotype animal model, which includes a step of administering zymosan A to a subject other than humans according to the present disclosure, an experimental animal model for Graves' ophthalmopathy, which simultaneously exhibits blepharitis, orbital tissue inflammation, and exophthalmos, may be obtained. In addition, the animal model prepared by the preparation method of the present disclosure may be advantageously used for researching the development of a therapeutic agent for Graves' ophthalmopathy the etiology of which has not been yet accurately revealed.