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.

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

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

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.

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.

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.

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. 

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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.

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.

 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. 

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.

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. 

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.

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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.

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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”).

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.

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.

Immune responses are crucial in fighting against infections. An uncontrolled immune response, however, can be deadly. Sepsis is one such inflammatory disease that can lead to organ failure and death, so it is crucial to develop new sepsis therapies. Long noncoding RNAs (lncRNAs), although not translated into proteins themselves, can regulate gene expression in biological processes. Studies have shown that lncRNAs can regulate immune responses, which leads to substantial interest in implicating lncRNAs in inflammatory diseases.

Gut microbiomes play central roles in health and disease. For example, the early-life gut microbiome is a simple yet rapidly changing ecosystem crucial for infant development. Early-life events, such as feeding, influence the succession of the gut microbiome. Breast milk is considered the preferred food source for infants due to its protection against infections and allergy development, among other benefits.  It remains unknown how to best recover a healthy microbiome following disturbance.  UC Berkeley researchers have developed a method of generating an in vitro microbiome that allows the discovery of treatments that enable recovery of infant gut microbiomes from a dysbiotic state. The invention provides the advantage of finding personalized treatments, thus minimizing side effects. A novel component is the use of microbial genome editing to eliminate specific microbial strains or to modify the capacities of specific members of personalized microbiomes to improve their performance or to eliminate pathogenicity factors. This will increase the chances of successful microbiome manipulation compared to more disruptive treatments, such as antibiotics or addition of organisms not normally resident in the native microbiome (e.g., probiotics).

Researchers at the University of California, Davis have developed agents made from terpenoids and salicylates that can be used as anesthetics in human and non-human animals, as well as environmentally friendly euthanasia agents in food-producing animals.