An In-Vitro Cell System Useful For Identification of RORgamma Antagonists

The retinoid-related orphan receptors alpha, beta and gamma (RORalpha, beta and gamma , also referred to as NR1F1, 2 and 3, respectively) comprise a distinct subfamily of nuclear receptors. Study of ROR-deficient mice has implicated RORs in the regulation of a number of biological processes and revealed potential roles for these proteins in several pathologies. NIH investigators have developed an in-vitro system using CHO cells stably expressing a TET-On expression vector regulating RORgamma and a RORE-Luciferase reporter.

Monoclonal Antibodies Against Poliovirus

Early work by Hammond at al. showed gamma globulin to be effective for the prevention of poliomyelitis. Therefore, passive immunotherapy could be another way to treat chronic excretors. Even though prior attempts to use intravenous immunoglobulin (IVIG) and breast milk were unsuccessful, there is reason to think that higher doses of antipoliovirus antibodies could result in complete clearance of poliovirus from chronically infected individuals.

Transgenic Mice Expressing Human Arginase II Gene in Endothelium: Useful for Studying Atherosclerosis and Other Vasculopathies

Cardiovascular disorders associated with endothelial dysfunction, like atherosclerosis, have decreased endothelial nitric oxide (NO) bioavailability. L-arginine, the primary substrate for endothelial nitric oxide synthase (eNOS), is important in the regulation of NO production. Arginase competes with eNOS for L-arginine and has been implicated in the endothelial dysfunction. NIH investigators have generated transgenic mice with human ArgII (hArgII) gene under control of endothelial-specific Tie2 promoter. In these mice, hArgII was expressed at very high levels in all tissues except liver.

Humanized Monoclonal Antibodies Efficient for Neutralization of Tick-Borne Encephalitis Virus (TBEV)

TBEV causes serious illnesses from meningitis to meningo-encephalitis, totaling 3,000 cases of hospitalization in Europe and between 5,000-10,000 cases in Russia reported every year. The Far Eastern hemorrhagic TBEV strains are associated with a mortality rate (between 1-2%), higher than other strains isolated in the Siberia or Western Europe. There is a high proportion (up to 46%) of TBEV patients with temporary or permanent neurological sequelae.

mGluR5 Tumor Mouse Model

Glutamate receptor mGluR5 has been reported to function in the brain. There were no prior reports of it being involved in melanoma. The NIH investigators have discovered that when over expressed in transgenic animals, mGluR5 induces melanoma. The establishment of an mGluR5 tumor mouse model will provide a unique opportunity to help elucidate the mechanisms underlying tumor formation, and allow the study of aggressive melanoma in animals and a screen of potential therapeutics. Such an mGluR5 tumor mouse model is established at the National Institutes of Health and is available for licensing.

Protease Deficient Bacillus anthracis with Improved Recombinant Protein Yield Capabilities

Species of Bacillus, such as Bacillus anthracis, Bacillus cereus, and Bacillus subtilis, are attractive microorganisms for recombinant protein production in view of their fast growth rate, high yield, and ability to secrete produced products directly into the medium. Bacillus anthracis is also attractive in view of its ability to produce anthrax toxin and ability to fold proteins correctly. This application claims a B. anthracis strain in which more than one secreted protease is inactivated by genetic modification.

Model Cell Lines With and Without AKT1 Mutations Derived from Proteus Syndrome Patients

The Proteus syndrome is a congenital disorder characterized by patchy overgrowth and hyperplasia (cell proliferation) of multiple tissues and organs, along with susceptibility to developing tumors. It is a rare disorder, with incidence of less than one case per million, caused by a somatic mutation. It is also a mosaic disorder, that is one in which cells of the same person have different genetic content from one another.

Transgenic Human Interleukin-21 Mouse Model

Available for licensing is a mouse model that constitutively expresses human interleukin-21 (IL-21). Traditionally, human IL-21 transgenic mouse models are difficult to produce as those with high IL-21 levels exhibit growth retardation and die before sexual maturity. The investigators generated transgenic mice that express human IL-21, which can stimulate murine cells in vitro thereby providing an accurate model to elucidate IL-21's role in immunity, immune disorders, and cancer.

Personalized Body Weight Management System Using Monitoring Devices and Mathematical Models of Metabolism

Attempts to manage body weight are often unsuccessful or only temporary. This is, in part, due to antiquated dieting methods that attempt to address calorie consumption while ignoring metabolic and physical changes. Personalized and more comprehensive methods to track and manage body weight may be more effective.

Small-Molecule Inhibitors of Human Galactokinase for the Treatment of Galactosemia and Cancers

Lactose, found in dairy products and other foods, is comprised of two simple sugars, glucose and galactose. In galactosemia, where galactose is not properly metabolized, build-up of toxic compounds, such as galactose-1-phosphate, can lead to liver disease, renal failure, cataracts, brain damage, and even death if this disorder is left untreated. Currently, the only treatment for galactosemia is elimination of lactose and galactose from the diet, but in some cases this is not sufficient to avoid long-term complications from the disorder.