The present invention includes compositions and methods for treating diseases or disorders associated with pathological calcification or pathological ossification. In certain embodiments, the diseases or disorders are selected from the group consisting of Generalized Arterial Calcification of Infancy (GACI), Idiopathic Infantile Arterial Calcification (IIAC), Ossification of the Posterior Longitudinal Ligament (OPLL), hypophosphatemic rickets, osteoarthritis, calcification of atherosclerotic plaques, PXE, hereditary and non-hereditary forms of osteoarthritis, ankylosing spondylitis, hardening of the arteries occurring with aging, calciphylaxis resulting from end stage renal disease and progeria.

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.

Provided herein are engineered transcription factors for selective upregulation of SCN1a and uses thereof for treating diseases and disorders, such as, Dravet syndrome. Also provided are microRNA binding sites and uses thereof for selective expression in parvalbumin neurons.

This disclosure pertains to methods and compositions for tolerizing a mammal's brain to exogenously administered acid sphingomyelinase polypeptide by first delivering an effective amount of a transgene encoding the polypeptide to the mammal's hepatic tissue and then administering an effective amount of the transgene to the mammal's central nervous system (CNS).

The invention in some aspects relates to recombinant adeno-associated viruses useful for targeting transgenes to CNS tissue, and compositions comprising the same, and methods of use thereof. In some aspects, the invention provides methods and compositions for treating CNS-related disorders.

Described herein are methods of treating muscular dystrophy comprising administering a self complementary recombinant AAV (rAAV) scAAVrh74.tMCK.hSGCA vector, methods of expressing alpha-sarcoglycan gene in a patient, pharmaceutical compositions comprising the rAAV, and methods of generating the rAAV.

The invention provides pluripotent cells that are used therapeutically for regenerating tissues but avoid rejection by subjects that receive them. In particular, the invention provides hypo-immunogenic pluripotent cells that avoid host immune rejection. The cells lack major immune antigens that trigger immune responses and are engineered to avoid phagocytic endocytosis. The invention further provides universally acceptable “off-the-shelf” pluripotent cells and derivatives thereof for generating or regenerating specific tissues and organs.

The present disclosure provides methods and compositions that include a polynucleotide that includes nucleic acids that encode an anti-idiotype polypeptide, as well as polypeptides that are encoded by the same, and cells that include and express the polypeptide. Disclosed methods include methods that utilize the anti-idiotype polypeptides as safety switches when they are used in combination with antibodies, include approved biologic antibodies, that include the recognized idiotype. Certain embodiments include anti-idiotype polypeptides and nucleotides encoding the same, that include an internal domain. This internal domain in some embodiments has functional domains that can induce proliferation or cell death upon binding of the anti-idiotype polypeptide by its target antibody.

The invention in some aspects relates to isolated nucleic acids, compositions, and kits useful for identifying adeno-associated viruses in cells. In some aspects, the invention provides kits and methods for producing somatic transgenic animal models using recombinant AAV (rAAV) to an animal having at least one transgene that expresses a small interfering nucleic acid or at least one binding site for a miRNA.

The invention provides compositions and methods for manufacturing pluripotent cells. In particular, the invention provides improved culture platforms for manufacturing pluripotent cells with ground state pluripotency.