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Topoisomerase 3B (TOP3B) is the only topoisomerase that can act on RNA as well as DNA, and thus has been a target of interest for the development of cancer therapies and RNA viral infection therapies. In the context of cancer, TOP3B is not an essential gene, but a subset of cancer cells with pre-existing genome instability are particularly vulnerable to the inactivation of TOP3B. While inhibitors for other topoisomerases are among the most potent and widely used anticancer agents, there are no known inhibitors of TOP3B.

There are five known Ebolavirus species: Ebola virus (Zaire ebolavirus); Sudan virus (Sudan ebolavirus or SUDV); Taï Forest virus (Taï Forest ebolavirus, formerly Cote d'Ivoire ebolavirus); Bundibugyo virus (Bundibugyo ebolavirus); and Reston virus (Reston ebolavirus). Last year an ebolavirus outbreak resulted in 164 cases and 55 deaths. While there is an FDA-approved Ebola virus vaccine authorized for use against Ebola virus infections, ERVEBO, this vaccine is not effective against SUDV due to the significant variation between Ebola virus and SUDV.

Human influenza A is one of two influenza virus types that cause seasonal epidemics of disease (known as flu season) almost every winter in the United States. Influenza A viruses are the only influenza viruses known to cause flu pandemics (i.e., global epidemics of flu disease). (Source.)

Influenza A and B viruses can cause seasonal flu epidemics ― commonly known as the “flu season” ― and infect the nose, throat, eyes, and lungs in humans. Typically, flu seasons that are dominated by influenza A (H3N2) virus activity have higher associated hospitalizations and deaths in at-risk groups, such as people ages 65 and older and young children. Influenza A (H3N2) virus can also cause respiratory disease in animals, such as canines and swine.

This technology includes an alpha-galactosidase-A knockout mouse model that can be used to study Fabry disease, an X-linked lysosomal storage disorder. Alpha-galactosidase-A is a crucial enzyme responsible for the breakdown of glycolipids, particularly globotriaosylceramide (Gb3), within lysosomes. In Fabry disease, a rare and inherited lysosomal storage disorder, mutations in the GLA gene lead to deficient or non-functional alpha-galactosidase-A enzyme activity.

Disorders of adult beta-globin synthesis, which include sickle cell disease (SCD) and beta-thalassemia, are the most common monogenic disorders in the world. While the curative potential of bone marrow transplantation has been demonstrated, this approach is limited to a small fraction of affected patients due to the requirement for an HLA-matched donor, the highly specialized approach that requires critical infrastructure, and the high cost.

Summary: 
Investigators at the National Institute on Drug Abuse seek co-development partners and/or licensees for collection of mu opioid receptor (MOR) agonists as alternatives for existing compounds.

Description of Technology: 
Although existing opioids are excellent analgesics and useful as positron emission tomography (PET) radiotracers, they come with debilitating side effects. These include addiction, respiratory distress, hyperalgesia, and constipation. Therefore, there is a need for alternatives with lower adverse effects.

N-acetylmannosamine (ManNAc) is a small uncharged physiological molecule that crosses membranes readily and is the natural precursor of intracellular sialic acid synthesis. NHGRI investigators discovered that ManNAc can be used for therapeutic purposes, including treating certain kidney diseases (e.g., those involving proteinuria and hematuria), resulting primarily or secondarily from hyposialylation (lack of sialic acid). Notably, ManNAc can also be used to treat diabetic nephropathy or diabetes.

The COVID-19 pandemic is a worldwide public health crisis with over 100 million confirmed cases and 2.4 million deaths as of February 2021. COVID-19 is caused by a novel coronavirus called SARS-CoV-2. SARS-COV-2 infects hosts via its spike (S) protein. The S protein contains the receptor binding domain (RBD) that binds to the angiotensin converting enzyme 2 (ACE2) receptor on human cells to facilitate viral entry and infection. There are few therapeutics available for COVID-19 patients that directly target SARS-CoV-2.

Recombinant immunotoxins (RITs) constitute a promising solution to hematologic cancers (e.g., Multiple Myeloma [MM]). RITs are chimeric proteins composed of a targeting domain fused to a bacterial toxin. Upon binding to a cancer cell displaying the target antigen, RITs are internalized, metabolized and the released toxin kills the cell. While highly active and effective, current RITs have short half-lives, requiring them to be used in high concentrations for treatment. At such high concentrations, RITs may show nonspecific activity and kill healthy cells.