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Purification of Glycosphingosines and Glycosphingolipids

Researchers at the University of California, Davis (UC Davis) have developed a simplified procedure to synthesize complex glycosphingosine compounds for the chemical preparation of glycosphingolipids.

(SD2021-427) Upregulation of cellular proteins using coronavirus-derived protein/peptides fused to RNA-targeting effectors

Researchers from UC San Diego developed an invention that enables protein expression to be upregulated using specific proteins and/or peptide sequences derived from SARS-CoV-2 proteins that are engineered to recognize specific mRNA transcripts by fusion to RNA-targeting modules such as CRISPR/Cas systems. They anticipate that these proteins can be fused or tethered to any engineered RNA-targeting moiety/module such as PUF/Pum, and pentatricopeptide proteins.

Novel therapy for inflammatory disease using fatty acid-bound alpha fetoprotein

α-Fetoprotein (AFP) is a fetal glycoprotein produced by the majority of human hepatocellular carcinoma tumors and other tumor types. Delineating differences between fetal 'normal' AFP (nAFP) and tumor-derived AFP (tAFP), investigators at UCSF and the Parker Institute for Cancer Immunotherapy have uncovered a novel role for tAFP in altering metabolism via lipid-binding partners. They have developed a pharmaceutical composition comprising AFP bound by a fatty acid which, depending on the fatty acid used, can have an immunosuppressive effect allowing for the treatment of inflammatory diseases.  AFP bound to other fatty acids can eliminate the immune suppressive impact and have a neutral effect which allows for the development of dendritic cell (DC) vaccines presenting AFP epitopes which could be used to treat and prevent tumor AFP-expressing cancers.  

Cellular Protein CDH4 Inhibiting Peptide

Researchers at the University of California, Davis have developed a unique peptide that induces cell differentiation by inhibiting cellular protein CHD4, a promising approach to target dedifferentiated cancer cells and for cell therapy.

Use Of Viral Il-6 To Modulate Monocyte Differentiation To Boost Anti-Tumor Immunity

Researchers at the University of California, Davis have developed a virally derived homolog to increase the inflammatory response desirable in cancer immunotherapy.

Transcription Active Complex Targeting Cancer Drug From Viral Protein Sequence

Researchers at the University of California, Davis have developed a viral peptide therapeutic that targets MYC-based cancerous tumors.

Novel molecular target and approach(es) for the bidirectional modulation of T-cell function

Researchers at UC Irvine have identified and tested a molecular target that regulates T cell function during chronic viral infection and cancer. The molecular target is one of the high mobility group proteins (HMGB2). HMGB2 is a DNA binding protein that regulates transcriptional processes, meaning that its modulation will have profound effects on T cell differentiation and ultimate function by altering the expression of many genes.

Recombinant Enhanced Antiviral Restrictors

Researchers at the University of California, Davis (“UC Davis”) have developed fusion proteins effective in inhibiting the replication of diverse groups of viruses that can be useful in controlling vector-borne virus transmission as well as reducing vector populations.

15LOX1 Inhibitor Formulation Determination For IV Administration

Lipoxygenases catalyze the peroxidation of fatty acids which contain bisallylic hydrogens between two cis double bonds, such as in linoleic acid (LA) and arachidonic acid (AA). Lipoxygenases are named according to their product specificity with AA as the substrate because AA is the precursor of many active lipid metabolites that are involved in a number of significant disease states. The human genome contains six functional human lipoxygenases (LOX) genes (ALOX5, ALOX12, ALOX12B, ALOX15, ALOX15B, eLOX3) encoding for six different human LOX isoforms (h5-LOX, h12S-LOX, h12R-LOX, h15-LOX-1, h15-LOX-2, eLOX3, respectively). The biological role in health and disease for each LOX isozyme varies dramatically, ranging from asthma to diabetes or stroke. The nomenclature of the LOX isozymes is loosely based on the carbon position (e.g., 5, 12, or 15) at which they oxidize arachidonic acid to form the corresponding hydroperoxyeicosatetraenoic acid (HpETE), which is reduced to the hydroxyeicosatetraenoic acid (HETE) by intracellular glutathione peroxidases. Lipoxygenase inhibitors are difficult to formulate due to challenges with solubility and other factors, therefore new formulations are needed.

ML351 As Treatment For Stroke And Ischemic Brain Injury

Lipoxygenases form a large family of enzymes capable of oxidizing arachidonic acid and related polyunsaturated fatty acids. One such lipoxygenase, 12/15 LOX can oxidize both the C-12 and C-15 of arachidonic acid, forming 12- or 15-hydroperosyarachidonic acid (12- or 15-HPETE). Lipoxygenases and their metabolites have been implicated in many diseases. In particular 12/15-LOX (also known as 15-LOX-1, 15-LOX, or 15-LO-1 in humans and L-12-LoX, leukocyte-type 12-LO, or L-12-LO in mice) plays a role in atherogenesis, diabetes, Alzheimer's, newborn periventricular leukomalacia, breast cancer, and stroke. Whatever the name, the protein is encoded by the gene ALOX15 in both mice and humans. Lox inhibitors are difficult to develop due to the mouse and human homologs having different substrate and inhibitor specificities - 12/15 LOX produces predominantly 15-HETE in humans and 12-HETE in mice. So existing inhibitors are not selective for 12/15 LOX with regard to other LOX isoforms. In addition, many are strong antioxidants and therefore may result in off-target effects. 

Gene Targets For Manipulating T Cell Behavior

Brief description not available


Chimeric antigen receptor (CAR) T cells have so far shown limited efficacy on brain and solid tumors. UCSF investigators have developed a method of manufacturing recombinant immune cells by pre-treating them with a combination of small molecules to increase the number of CAR T cells in the tumor microenvironment and improve the survival of animal models bearing glioma in the brain relative to CAR T cells that have not received the pre-treatment. These results may be applicable to other solid tumors.

Improved laser wakefield acceleration-based system for cancer diagnostics and treatment

Researchers at UC Irvine have developed methods to facilitate the delivery of a high dose, low energy electron beam or X-ray in a compact manner.

Piericidin A1 And The Piericidin Derivative Mer-A 2026B As Inhibitors Of The Bacterial Type III Secretion System

 As currently available antibiotics become ineffective due to the rise in antibiotic resistance among pathogenic bacteria, development of completely new classes of antibiotics is critical. Classic antibiotics target pathogens and commensal bacteria indiscriminately; therefore, their use puts selective pressure on both populations. Because of the abundance of commensals within a mammalian host, antibiotic resistance is thought to arise more frequently in commensal bacteria and is horizontally transferred to pathogens. In contrast to classic antibiotics, virulence blockers are compounds that selectively inhibit the expression or function of a virulence factor in a pathogen or group of pathogens. Advantages of virulence blockers are twofold. For one, selective pressure on a limited number of microbes, i.e., only pathogens expressing the molecular target of the virulence blocker, should limit the evolution of resistance. Second, the decreased commensal killing by virulence blockers has the potential to preserve a healthy microbiota, which is critical for maintaining gut homeostasis and defending against opportunistic pathogens. Type III secretion systems (T3SS) are bacterial appendages required by dozens of pathogens to cause disease, including Salmonella, enteropathogenic Escherichia coli (EPEC), Shigella, Pseudomonas, and Yersinia, but they are largely absent in nonpathogenic bacteria. Bacteria use T3SS to inject bacterial effector proteins into target host cells to manipulate host processes for the benefit of the pathogen. Seven T3SS injectisome families have been identified and share a number of homologous membrane-associated components with the flagellar basal body. Agents that target T3SS would be key virulance blockers for a set of pathogens that are very important to human and animal health as are methods of screening for such agents. 

High-Throughput Discovery Of Bipartite Or Tripartite Crispr-Based Epigenetic Editors

Currently, conventional methods of epigenome editor discovery require time and labor-intensive construct development, which is typically performed in low-throughput arrayed formats. The platform bypasses current time/labor constraints (and without reliance on construct barcodes) to facilitate the identification of an optimal gene modulator in a single experiment.

Makaluvamine Analogues For Development As Anticancer Agents

Marine sponges and microorganisms are the source of many promising bioactive products for use in the treatment of cancer. Multicompound libraries can be readily generated from these sources for comprehensive bioactivity and biosynthetic investigations. Prior studies into these organisms/communities involved examination of Zyzzya sponge metabolites and corresponding bacterial communities from this genus. One particularly potent compound was a makaluvamine extracted from a Zyzzya fulginosa sponge from Papua New Guinea was highly active on PANC-1 cells.  Additional studies show that the key structure of malakuvamine and other related compounds is a pyrrolo[4,3,2-de]quinoline motif now seen in 100 similar natural products. 

Mitochondria Targeting Photosensitizer for Photodynamic Therapy

Researchers at the University of California, Davis have developed a self-assembling, fibrous photosensitizer that targets mitochondria in tumor cells for destruction via photodynamic therapy with enhanced localization and potency.

(SD2020-447) An anti-inflammatory peptide

UC San Diego researchers synthesized a cell‐penetrating NEMOActPep where the NEMO peptide was fused to a peptide known to penetrate cell membrane. They also synthesized the corresponding mutant version where all six critical amino acids within this NEMOActPep were mutated to glycines.Currently, UC San Diego is looking for a company interested in developing US Patent Rights.

Soluble Epoxide Hydrolase Inhibitors For The Treatment Of Arrhythmogenic Cardiomyopathy And Related Diseases

Researchers at the University of California, Davis have developed an effective drug therapy, utilizing Soluble Epoxide Hydrolase (sEH) inhibitors, to prevent sudden death and treat the progression of myocardial dysfunction in patients with Arrhythmogenic Cardiomyopathy (“ACM”).

Pharmacological fortification and/or restoration of protective nerve coverings via a novel therapeutic target

Researchers at UC Irvine have discovered a novel mechanism by which restoration of protective nerve coverings fails in degenerative disease like multiple sclerosis. While therapeutics to slow disease progression exist, there are currently none aimed at preventing or restoring damage to nerve coverings.

Compositions and Methods for Genome Editing

RNA-mediated adaptive immune systems in bacteria and archaea rely on Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) genomic loci and CRISPR associated (Cas) proteins that function together to provide protection from invading viruses and plasmids. Genome editing can be carried out using a CRISPR-Cas system comprising a CRISPR-Cas effector polypeptide and a guide nucleic acid, such as a guide RNA. However, unintended chromosomal abnormalities following on-target genome editing, such as chromosome loss, are potential concerns for genome editing. UC Berkeley researchers and others have developed a method to modulate the expression levels of the DNA damage response factor p53 in order to mitigate chromosomal abnormalities that occur after genome editing by nucleases like Cas9. The invention provides treatment methods by generating a modified cell and then administering the modified cell to an individual in need thereof and compositions having a CRISPR-Cas effector polypeptide, a guide nucleic acid, and an agent that increases the level of a p53 polypeptide in a mammalian cell.

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