Enzymatically-Active RNA-Dependent RNA Polymerase From a Human Norovirus (Calicivirus)

The noroviruses (formerly known as “Norwalk-like viruses”) are associated with gastroenteritis outbreaks, affecting large numbers of individuals each year. Emerging data are supporting their increasing recognition as important agents of diarrhea-related morbidity and mortality. The frequency with which noroviruses are associated with gastroenteritis as “food and water-borne pathogens” has led to the inclusion of caliciviruses as Category B Bioterrorism Agents/Diseases.

Construction of an Infectious Full-Length cDNA Clone of the Porcine Enteric Calicivirus RNA Genome

Porcine enteric calicivirus (PEC) is a member of the genus Sapovirus in the family Caliciviridae. This virus causes diarrheal illness in pigs, and is presently the only enteric calicivirus that can be grown in cell culture. In addition to its relevance to veterinary medicine as a diarrheal agent in pigs, PEC serves as an important model for the study of enteric caliciviruses that cause diarrhea and that cannot be grown in cell culture (including the noroviruses represented by Norwalk virus).

Multimeric Protein Toxins to Target Cells Having Multiple Identifying Characteristics

This technology relates to multimeric bacterial protein toxins which can be used to specifically target cells. Specifically, this is a modified recombinant anthrax toxin protective antigen (PrAg) that has been modified in several ways. First, the PrAg can be activated both by a metalloproteinase (MMP) and by urokinase plasminogen activator (uPA). Second, the native PrAg lethal factor (LF) binding site has been modified so that only a modified PrAg comprising two different monomers can bind anthrax LF.

Small Molecule Inhibitors of Clk and Dyrk Kinases for Potential Therapeutic Intervention of Down Syndrome, Alzheimer's Disease and Cancer

This technology includes small molecule inhibitors of the cdc2-like kinase (Clk) and Dyrk kinase which can restore splicing outcomes within many dysregulated splicing events potentially reversing phenotypes associated with diseases associated with abnormal splicing. The Clks regulate the alternative splicing of microtubule-associated protein tau and are implicated in frontotemporal dementia and Parkinson's disease through the phosphorylation of splicing factors (SF).

Identification and Use of 12/15-Lipoxygenase (LOX) Inhibitors for Post-Strike Treatment

This technology includes the identification and use of 12/15-lipoxygenase (LOX) inhibitors, including ML351 and related analogs, for post-stroke treatment. The 12/15-LOX directly oxidizes lipid membranes leading to their direct attack. After a stroke, the activity of 12/15-LOX is upregulated and is thought to contribute to increased neuronal loss and blood-brain barrier leakage. A high-throughput screen was undertaken to find inhibitors, which were then subjected to medical chemistry optimization.

Compounds and Methods for Treating Brain Injury

This technology includes MRS4322, which is an A3 agonist that is currently being evaluated for treatment of traumatic brain injury. Although its affinity in the receptor is in the micromolar range, it enters the brain in sufficient concentration to activate a protective CNS receptor, A3 adenosine receptor. Potential applications of such A3 agonists could also include neurodegenerative conditions.

Replicative-Defective Mutant Human Cytomegalovirus: Potential Applications in Vaccinology and Cancer Immunotherapy

The potential applications of a replicative-defective mutant form of human cytomegalovirus (HCMV) are significant in the fields of vaccinology and cancer immunotherapy. This innovative approach involves engineering a mutant HCMV that can selectively target specific cells. Firstly, it holds promise as a vaccine candidate for protecting against HCMV infection, given the success of a similar strategy against herpes simplex virus in animal models.

Bispecific Antibody Targeting Anthrax Toxins and Capsule for Enhanced Biodefense

The technology focuses on the development of a tetravalent bispecific antibody effective against Bacillus anthracis, the bacterium responsible for anthrax. This antibody combines the specificities of two monoclonal antibodies (mAbs): one targeting anthrax protective antigen (PA) and the other targeting the bacterial capsule. The anti-PA mAb shows potent toxin-neutralizing activity, while the anti-capsule mAb efficiently kills anthrax bacteria.

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