This technology includes the development of selective P2Y14R antagonists for the treatment of asthma, sterile inflammation of the kidney, diabetes, and neurodegeneration. The P2Y14 receptor (P2Y14R) is a target for the treatment of inflammatory diseases, including pulmonary and renal conditions. Selective P2Y14R antagonists have demonstrated efficacy in animal models of asthma, pain, diabetes, and acute kidney injury. However, the prototypical antagonist is not optimal for in vivo administration, as it displays a low oral bioavailability.

This technology includes the creation and use of A3 adenosine receptor (A3AR)-selective agonists for treating chemotherapy-induced peripheral neuropathy, chronic neuropathic pain, rheumatoid arthritis, psoriasis, and other conditions. A3 receptors for adenosine are found in most cells and endogenous activation of the A3 receptors can result in apoptosis, thereby relieving the inflammation or targeting a tumor. A3AR agonists have been a promising strategy for the treatment of various diseases.

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.

This technology includes apoE-apoCII chimeric peptides that possess the ability to lower the triglyceride level both in vitro and in vivo. These peptides can be used for treating hypertriglyceridemia and alleviating other diseases and conditions associated with increased triglycerides.

This technology includes a new chemical scaffold (with lead compound XL5) against hRpn13 that induces apoptosis, which may have clinical efficacy against cancer. The structure of XL5-conjugated hRpn13 guided the design of XL5-PROTAC degrader compounds that exhibit greater efficacy than previous hRpn13-targeting compounds, as evaluated by selectivity for hRpn13, induction of apoptosis, and loss of cell viability. In cells, XL5-PROTACs revealed the presence of a truncated hRpn13 product that binds to proteasomes and is selectively degraded by XL5-PROTACs.

This technology includes irradiated Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV-LCL) as feeder cells for the ex vivo expansion of natural killer (NK) cells. EBV-LCL feeder cells, altered by radiation to prevent uncontrolled growth, provide a supportive environment for NK cells to multiply effectively. This method addresses the challenge of obtaining sufficient quantities of functionally active NK cells, which are crucial components of the immune system known for their ability to target and destroy tumor cells and virally infected cells.

This technology includes genetic manipulation of natural killer (NK) cells to express thrombopoietin receptor (c-MPL) growth factor receptor as strategy to augment NK cell proliferation and anti-tumor immunity. Many investigational adoptive immunotherapy regimens utilizing NK cells require the administration of IL-2 or IL-15 cytokines to support the survival and function of the cells in patients, however administration of these cytokines causes a number of serious dose-dependent toxicities.

This technology includes an efficient lentiviral vector-based method for gene transfer into NK cells and demonstrates a stable and long-term robust expression of transgenes for the treatment of cancer. High gene transfer rates into primary cells being transduced and the ability to produce high titers of virus particles for large-scale transduction of patient cells are prerequisites for clinical trials. Lentiviral vectors can be produced in high titer and concentrated without compromising their transduction efficiency.

This technology includes a new method to prepare very long chain fatty acids (VLCFA), which does not use the previously reported toxic mercury amalgam, for use as nutritional supplements, and as therapeutics for various diseases. The key coupling step involves an organocopper mediated coupling of the Grignard regent derived from the bromo alkyl tetraene with a bromoalkyl containing a protected alcohol. After the coupling the alcohol Is deprotected and oxidized to prepare the very long fatty acid. The synthetic approach is flexible and can be used to prepare the other VLCFA compounds.

This technology includes a new class of synthetic peptides that activate Lipoprotein Lipase (LPL), a key plasma enzyme that lowers triglycerides, by displacing apoC-111, a potent inhibitor of LPL. ApoC-11 is a known activator of LPL, whereas ApoC-111 inhibits LPL and raises triglycerides either directly by blocking lipolysis and or by preventing hepatic uptake of lipoproteins. Both apoC-II and apoC-III have to bind to the surface of a lipoprotein particle to mediate their effects.