Disclosed herein are rodents (such as, but not limited to, mice and rats) genetically modified to comprise a humanized Tslp gene, a humanized Tslpr gene, a humanized 117ra gene, or a combination thereof. Compositions and methods for making such genetically modified rodents, as well as methods of using such genetically modified rodents as an animal model for diseases such as allergic diseases and cancer are provided.

Disclosed are methods of administering AAV viral-based vector compositions useful in delivering a variety of nucleic acid segments and compositions comprising an agent, such as an immunosuppressive agent. Methods and compositions comprising a combination therapy are provided. The disclosed AAV vector compositions include 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. The compositions comprising an agent may comprise a sphingosine analog, a glucococorticoid, an mTOR inhibitor, and/or a targeted biologic.

[Problem] The objectives of the present invention are to provide a method for making an animal that has been stressed, in particular, chronically stressed, affect or develop a specific disease or symptom, and, through elucidating the process from loading stress to affection or onset of the disease or symptom, to provide a useful tool for research and development of preventing or treating methods of the disease or symptom. [Solution] The present invention relates to a method for producing a disease modeling non-human animal having cerebrovascular inflammation, the disease modeling non-human animal, a method for screening a drug using the disease modeling non-human animal, a method for determining the risk of a disease using the presence of cerebrovascular inflammation as an indicator, and a pharmaceutical for preventing and/or treating progressive multiple sclerosis or the like. The present invention enables developing pharmaceuticals for the above described diseases or the like and performing researches for elucidating their pathogenic mechanisms. The present invention also enables determining the risk of affection or onset of progressive multiple sclerosis or the like and preventing and/or treating progressive multiple sclerosis or the like.

The present invention provides compositions and methods for treating joint disorders that are characterized by an inflammatory component. In some aspects, the compositions and methods are to prevent the progression of osteoarthritis and other arthritides and to treat osteoarthritis and other arthritides in a mammalian joint.

Non-human animals comprising a human or humanized C3 and/or C5 nucleic acid sequence are provided as well as methods for using the same to identify compounds capable of modulating the complement system. Non-human animals that comprise a replacement of the endogenous C5 gene and/or C3 gene with a human or humanized C5 gene and/or C3 gene, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized C5 gene under control of non-human C5 regulatory elements is also provided, including non-human animals that have a replacement of non-human C5-encoding sequence with human C5-encoding sequence at an endogenous non-human C5 locus. Non-human animals comprising a human or humanized C3 gene under control of non-human C3 regulatory elements is also provided, including non-human animals that have a replacement of non-human C3 protein-encoding sequence with human or humanized C3 protein-encoding sequence at an endogenous non-human C3 locus. Non-human animals comprising human or humanized C3 and/or C5 sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.

The present invention relates to a non-human mammalian animal which has been modified to have in the blood, plasma and/or serum (a) an increased number of leukocytes and/or neutrophils, and (b) a reduced activity of the DNase 1 and/or DNase 1-like 3 enzymes. The non-human mammalian animal is particularly suitable for studying inflammation and/or a disease associated with inflammation. In a further aspect, the invention relates to the use of the non-human mammalian animal as a model for identifying therapeutic or diagnostic targets of inflammation and/or a disease associated with inflammation. In a still further aspect, the invention relates the use of the non-human mammalian animal as a model for drug candidate testing. In addition, a method for testing an anti-inflammatory drug candidate against extracellular DNA is provided. Finally, a method for testing an anti-inflammatory drug candidate for modifying the formation or degradation of neutrophil extracellular traps is provided. In still another aspect, the present invention relates to a non-human mammalian animal, which has been modified to have an increased number of neutrophils in blood.

The present invention relates to a composition for preventing or treating skin diseases, comprising a skin-penetrating nucleic acid complex as an effective component, and more specifically, to a pharmaceutical composition or a cosmetic composition for preventing, alleviating, or treating atopic dermatitis, comprising a skin-penetrating nucleic acid complex in which a carrier peptide nucleic acid and a bioactive nucleic acid targeting TLR2 or IL-4Rα are connected by complementary binding. The skin-penetrating nucleic acid complex according to the present invention, in which the carrier peptide nucleic acid and the bioactive nucleic acid targeting TLR2 or IL-4Rα are connected by complementary binding, has high skin permeation and skin retention, and thus is useful in the prevention, alleviation or treatment of skin diseases such as atopic dermatitis.

The present disclosure relates to methods and compositions for modulating immune responses, methods of treating or preventing diseases such as autoimmune and inflammatory disorders and cancer, as well as methods of enhancing immune responses to antigens and for the treatment of infectious diseases.

Disclosed herein are nucleic acids encoding for and proteins expressing chimeric C1q polypeptides, non-human animals comprising said nucleic acids, and methods of making or using said non-human animals.

Non-human animals comprising a human or humanized C3 and/or C5 nucleic acid sequence are provided as well as methods for using the same to identify compounds capable of modulating the complement system. Non-human animals that comprise a replacement of the endogenous C5 gene and/or C3 gene with a human or humanized C5 gene and/or C3 gene, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized C5 gene under control of non-human C5 regulatory elements is also provided, including non-human animals that have a replacement of non-human C5-encoding sequence with human C5-encoding sequence at an endogenous non-human C5 locus. Non-human animals comprising a human or humanized C3 gene under control of non-human C3 regulatory elements is also provided, including non-human animals that have a replacement of non-human C3 protein-encoding sequence with human or humanized C3 protein-encoding sequence at an endogenous non-human C3 locus. Non-human animals comprising human or humanized C3 and/or C5 sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.