Rescue of AAV Production by shRNA Co-transfection

Recombinant adeno-associated virus (rAAV) vectors are proving to be a valid, safe and efficient gene transfer system for clinical applications. As most vectors utilize constitutive promoters, this results in transgene expression in the producer cell. Some of these transgene products can induce proapoptotic, cytostatic or other unknown effects that interfere with producer cell function. Therefore, this reduces the viral vector yield and is a major limitation when trying to characterize poorly described genes.

Human lgA Monoclonal Antibody that Targets a Conserved Site on the Plasmodium Falciparum Circumsporozoite Protein

Scientists at NIAID have isolated MAD2-6, an IgA antibody active against Plasmodium falciparum sporozoites, the infectious agent of malaria. In 2019, the majority of the 229 million cases resulted from P. falciparum infections. Because P. falciparum has a complex lifecycle during human infection, most advanced malaria vaccine candidates and current chemoprophylaxis drugs can confer only partial, short-term protection in malaria-endemic areas. Thus, the MAD2-6 antibody could be used alone or in combination with current technology.

SIRT2 Inhibitors as Novel Therapeutics for Myocardial Infarction and Ischemic Stroke and to Prevent Necrosis

Sirtuin 2 (SIRT2) inhibitors to reduce necrosis and, thereby, as novel therapeutics to treat ischemic stroke and myocardial infarction. Accumulating evidence indicates that programmed necrosis plays a critical role in cell death during ischemia-reperfusion. NIH investigators have shown that the NAD-dependent deacetylase SIRT2 binds constitutively to receptor-interacting protein 3 (RIP3) and that deletion or knockdown of SIRT2 prevents formation of the RIP1-RIP3 complex in mice.

Rapid and Sensitive Detection of Nucleic Acid Sequence Variations

The ability to easily detect small mutations in nucleic acids, such as single base substitutions, can provide a powerful tool for use in cancer detection, perinatal screens for inherited diseases, and analysis of genetic polymorphisms such as genetic mapping or for identification purposes. Current approaches make use of the mismatch that occurs between complimentary strands of DNA when there is a genetic mutation, the electrophoretic mobility differences caused by small sequence changes, and chemicals or enzymes that can cleave heteroduplex sites.

Autodock Vina Software Process for Efficient Large-Scale Cognate Ligand Screening

The invention pertains to software processes, additions, and docking approaches to Autodock Vina that speeds the rate and efficiency of analyzing ligand interactions with a receptor by cognate ligands and rewards conformations in the scoring algorithm for residue interactions that are based on the biological data. The score is multiplied by a weighting factor to control the degree of ligand-residue interactions that are considered. This multiplier is then added to the docking score for confirmation.

Generation of Smad3-null Mice and Smad4-conditional Mice

SMADs are a novel set of mammalian proteins that act downstream of TGF-beta family ligands. These proteins can be categorized into three distinct functional sets, receptor-activated SMADs (SMADs 1,2,3,5, and 8), the common mediator SMAD (SMAD 4), and inhibitory SMADs (SMADs 6 and 7). SMAD proteins are thought to play a role in vertebrate development and tumorigenesis.

A Broadly Protective Human Antibody for GI Genogroup Noroviruses

Norovirus is a leading cause of vomiting, diarrhea, and foodborne illness worldwide, with 700 million cases and 200,000 deaths occurring each year. Despite decades of work in the field, there are no preventive or therapeutic strategies specifically approved for even the most prevalent forms of human norovirus (i.e., GI, GII genogroups), which are highly contagious and carry an increased risk of severe complications in children, older adults, and those with immunocompromising conditions. 

A Novel Strategy to Produce 6-cys Proteins Based on Pfs230D1 Domain Fusions

The Plasmodium parasite has a complex lifecycle during human infection and in the mosquito vector. Most advanced malaria vaccine candidates can confer only partial, short-term protection in malaria-endemic areas. A means of breaking the transmission of malaria to subsequent individuals could prevent a significant amount of human disease.

The primary embodiments of this technology are novel compositions of matter that produce enhanced transmission-blocking responses over current transmission blocking vaccines:

Broadly neutralizing influenza hemagglutinin stem-directed antibodies

In 2023, the World Health Organization (WHO) reported roughly 3 to 5 million cases of severe influenza worldwide, resulting in approximately 290,000 to 650,000 deaths. Given the high disease burden, the needs for both prophylactic and therapeutic influenza strategies remain significant. However, current treatments for influenza are susceptible to resistance and are useful for only a limited post-infection period.    

PIM-Targeted PROTACs

Proviral Integration for the Moloney murine leukemia virus (PIM) kinases are overexpressed in many solid cancers – including prostate, breast, colon, endometrial, gastric and pancreatic. High of PIM1 expression is predictive of poor survival in multiple cancer types. While several selective pan-PIM inhibitors were developed and tested in clinical trials, all ultimately increased PIM1-3 protein levels and developed intrinsic resistance. 

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