An in vivo method of modifying a genome of a target cell in a mammalian subject is described. The method includes administering an effective amount of a transducer cell to the subject, where the transducer cell includes a regulated viral vector delivery system (RVVDS) for producing and releasing viral transduction particles (VTPs) when the transducer cell is exposed to inducing conditions, and each VTP comprises a nucleic acid encoding a genome modification system (GMS) comprising a genome modification protein and one or more elements that regulate expression or activity of the genome modification protein in a mammalian cell.

Provided herein, in some embodiments, are methods for modulating expression and/or activity of transient receptor potential cation channel subfamily C, member 3 (TRPC3), as well as methods of treating Alzheimer's disease.

A method is provided to enhance repair or regeneration of a mammalian cardiovascular system to include heart and/or vasculature comprising: administering to a mammal in need thereof a composition comprising an effective amount of an agent that elevates levels of Smo, Ptc1, Shh, Ihh, Dhh, Gli1, Gli2, or Mycn.

The present invention provides an adeno-associated virus (AAV) vector gene therapy for use in treating a monogenic form of nephrotic syndrome, wherein the AAV vector comprises a NS-associated transgene and minimal nephrin promoter NPHS1 or podocin promoter NPHS2.

The present disclosure provides a chimeric non-human animal comprising human hepatocytes, methods for preparing the chimeric non-human animal comprising human hepatocytes and methods of utilizing the chimeric non-human animal comprising human hepatocytes to screening and identifying metabolites for any type of drugs, typically small molecule drugs, which might affect human liver functions and any other bodily function.

Bag3 is a multifunctional protein expressed predominantly in the heart, the skeletal muscle, the central nervous system and in many cancers. Although BAG3 was cloned only a decade ago, studies have shown that genetic variants, particularly those that result in haplo-insufficiency, can lead to severe left ventricular dysfunction; however, the full mechanisms responsible have remained obscure. To obviate the influence of heart failure itself on the biology of Bag3, ransgenic mice harboring a single allele knock-out were studied between 8 and 10 weeks of age before any obvious signs of heart failure were evident. The results were surprising and informative. First, it was found that despite a normal phenotype, young Bag3.sup.+/− had marked changes in the proteome that were characterized by changes in proteins associated with metabolism and apoptosis. Consistent with this finding, a decrease in the levels of critical proteins charged with maintaining the mitochondrial membrane potential was observed. It was also found that young mice shifted from a balance between the extrinsic and intrinsic pathways of apoptosis. However, in the presence of stress and the absence of Bag3 there was a shift from a balanced to an extrinsic dominant system (cleaved caspase 8). The diverse array of critical pathways regulated by Bag3 suggests a more important role especially during stress and that this role might include serving as an intracellular glue that holds proteins where they can be most effective rather than having them meet accidentally.

Disclosed are novel treatments for diseases and conditions caused by, directly or indirectly, high blood glucose levels increased gluconeogenesis. Such disease and conditions include, but are not limited to, type II diabetes, obesity, and cardiovascular conditions. Sam68, an RNA-binding adaptor protein and Src kinase substrate, is a novel regulator of hepatic gluconeogenesis and global and hepatic deletions of Sam68 significantly reduce blood glucose levels and the glucagon-induced expression of gluconeogenic genes. The treatments described herein may include inhibition of the activity of Sam68.

A pharmaceutical composition suitable for preventing or treating cardiac arrhythmia is disclosed. The pharmaceutical composition contains, as an active ingredient, a CCN5 protein or a nucleotide encoding the CCN5 protein. The pharmaceutical composition inhibits the pathological activity of CaMKII, which induces cardiac electrical abnormalities that is the main cause of atrial arrhythmia and ventricular arrhythmia, so as to restore the electrical functions, and inhibits the activity of myofibroblasts causing structural abnormalities. Therefore, the pharmaceutical composition can be effectively used in the prevention or treatment of cardiac arrhythmia.

The invention relates to a combination of a FGFR inhibitor and an EZH2 inhibitor for use in a method of treating a patient suffering from a BRCA1-associated protein 1 (BAP1) negative cancer. The invention further relates to a pharmaceutical preparation, comprising a FGFR inhibitor and an EZH2 inhibitor, to the use of said pharmaceutical preparation in a method of treating BAP1-negative cancer, to methods of identifying a patient with cancer, who is eligible for treatment with a combination of a FGFR inhibitor and an EZH2 inhibitor, and to a mouse model for mesothelioma.

The present invention relates to a method of screening for a cancer therapeutic agent using Cyclin B1, Cyclin-dependent kinase 1 (CDK1), and retinoic acid receptor responder 1 (RARRES1), and a composition for diagnosing cancer or predicting a prognosis using the same. As a result of having conducted intensive studies to discover molecular mechanisms for diagnosing cancer and predicting a prognosis, the inventors of the present invention confirmed that in cancer-derived samples, according to the degree of mutual binding between RARRES1 and CDK1 or Cyclin B1, the mitosis of cancer cells was arrested, the formation of CDK1-Cyclin B1 complexes was suppressed, and the degradation of these proteins was promoted, and thus RARRES1 was a crucial factor in the diagnosis of cancer, prognosis prediction, and the treatment of cancer. In addition, through these findings, it is anticipated that RARRES1 may be widely used in screening for a cancer therapeutic agent exhibiting a decrease in the degree of binding between CDK1 and Cyclin B1, an increase in the degree of binding between the RARRES1 gene and CDK1 or Cyclin B1, and a decrease in an amount or activity of the CDK1 protein or the Cyclin B1 protein, and in the development of drugs. In addition, the present invention relates to a targeting vector including a portion of the Rarres1 gene and sequences used in producing a conditional knockout animal model, an animal cell for producing a tumorigenic animal model, which is produced using the targeting vector, a tumorigenic Rarres1.sup.−/− animal model produced using the animal cell, a method of producing the animal model, and a method of screening for a cancer therapeutic agent by using the method. Thus, as a result of having conducted intensive studies to discover molecular mechanisms for diagnosing cancer and predicting a prognosis, the inventors of the present invention confirmed that a Rarres1.sup.−/− animal model was prone to spontaneous tumors and exhibited increased phosphorylation of CDK1 and Cyclin B1 and a high activity of a CDK1-Cyclin B1 complex, and thus it was confirmed that the tumor cell cycle progression was unusually rapid due to a decrease in protein degradation ability. In particular, it was confirmed that stem cell proliferation was increased, and chromosomes were unstable upon induction of mitotic defects and mitosis, from which it was confirmed that RARRES1 is a crucial factor in diagnosing cancer, predicting a prognosis, and treating cancer. Moreover, it is anticipated that the Rarres1.sup.−/− animal model can be variously used for screening for a cancer therapeutic agent and developing a drug, through the relationship between RARRES1