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Electrochemical Flash Fluorination and Radiofluorination

Researchers led by Saman Sadeghi from the Department of Molecular & Medical Pharmacology at UCLA have developed a new and simple process to make fluorinated organic compounds.

Chemical reagents for natural and modified nucleoside triphosphates synthesis

Traditional synthesis of nucleoside triphosphates (NTPs), the building blocks of our genetic material, requires expensive purification yet produces small scale quantities. UCI researchers have developed novel reagents as well as a synthetic route that enables cost-effective and larger scale production of NTPs critical for biomedical research, as well as in certain diagnostic and therapeutic modalities.

Methods for Enhancing Cell Populations for Articular Cartilage Repair

Cartilage lesion treatments require expanding cells from healthy donor cartilage which have limited availability and restricted potential to produce cartilage. This invention overcomes these challenges, presenting chemical and physical methods for enhancing cell populations capable of producing neocartilage. According to a 2015 global market report, tissue engineering technologies are expected to reach over 94B USD by 2022.

Methods for Producing Neocartilage with Functional Potential

Cell expansion for cartilage tissue production usually leads to loss of the potential to produce cartilage, which impedes uses for cartilage repair. This invention features methods and systems for producing highly expanded primary cells to construct functional neocartilage and other neotissue. According to a 2015 global market report, tissue engineering technologies are expected to reach over 94B USD by 2022.

Small RNA Extraction Kit with High Yield

Prof. Wenwan Zhong and her lab at UCR have developed a method to recover small RNAs using TiO2 fibers which results in a 200-fold improvement in yield when compared to commercially available SiO2 columns. Fig. 1 Schematic of the steps involved in recovering small RNAs using TiO2 fibers and a unique protocol to wash and elute the small RNA.   Fig. 2 Extracting miRNA from MDA-MB-231 cells with TiO2 fibers and SiO2 PureLink miRNA isolation columns. Higher recoveries of endogenous hsa-miR-21 were found with TiO2 fibers when compared with PureLink columns.

The Brightest, Red-Shifted Luciferase-Luciferin Bioluminescent Pairs

Researchers at the University of California, Riverside, have developed several new luciferase-luciferin pairs that have superior brightness and excellent performance in vitro and in vivo. Through directed evolution of the existing NanoLuc Luciferase and the use of diphenylterazine (DTZ) as a substrate, the emission extensity is more than doubled compared to NanoLuc-furimazine. Moreover, red-shifted emission of teLuc-DTZ makes it an excellent tool for in vivo imaging. teLuc-DTZ streamlines a variety of applications to afford high sensitivity and reproducibility. Furthermore, fusing teLuc to a fluorescent protein creates the Antares2-DTZ pair, with emissions further red-shifted to the > 600 nm range and 65 times more photons emitted above 600 nm than FLuc-D-Luciferin. Fig. 1 shows the relative emission intensity and the range of emitted wavelengths of light  

Hydrogel Scaffold for 3D Tissue Culture

Prof. Jin Nam and his colleagues at the University of California, Riverside have developed a hybrid scaffold which combines a thermosensitive hydrogel, poly(ethylene glycol)-poly(N-isopropylacrylamide) (PEG-PNIPAAm), with a biodegradable polymer, poly(ε-caprolactone) (PCL), into a composite, electrospun microfibrous structure. The electrospun structure enables a structurally self-supporting hybrid scaffold which requires a simple inoculation of cell-containing media to encapsulate cells in a 3D hydrogel within a network of PEG-PNIPAAm/PCL microfibers. This novel hybrid scaffold enhanced chondrogenic differentiation of human mesenchymal stem cells (hMSCs), resulting in superior mechanical properties of the cell/scaffold constructs as compared to those of the pure forms of its constitutive components. The hybrid scaffold enables a  single-step uniform cell seeding process to inoculate cells within a 3D hydrogel with the potential for various tissue engineering applications. Figure 1. Schematic of electrospun hybrid scaffolds for moldless 3D cell encapsulation in hydrogel. Thermosensitive PEG-PNIPAAm composited with PCL was electrospun to produce thick (~ 2.5 mm) hybrid scaffolds composed of micro-sized fibers. Large pores allow uniform cell infiltration upon seeding throughout the thickness of the scaffolds at room temperature. Subsequent increase in temperature to 37 °C induces the PEG-PNIPAAm to gelate to encapsulate the uniformly seeded cells in 3D.  

17S-FD-895: An Improved Synthetic Splice Modulator mirroring FD-895

The spliceosome, the cellular splicing machinery, regulates RNA splicing of messenger RNA precursors (pre-mRNAs) into maturation of protein coding RNAs. Recurrent mutations and copy number changes in genes encoding spliceosomal proteins and splicing regulatory factors have tumor promoting or suppressive functions in hematological malignancies, as well as some other cancers. Over the past 10 years, a list of natural products, including FD-895, pladienolide B, herboxidiene, and spliceostatin A, have been identified as spliceosome modulators. They have been shown to have anti-cancer effect in vitro and in vivo models. However, these compounds demonstrate poor metabolic stability and short half-lives in vivo, excluding them from entering clinical evaluation. This invention, 17S-FD-895, is an analog of FD-895 and was synthesized through the combination of total synthesis and synthetic methods, demonstrating improved stability and on-target effect. This new spliceosome targeting compound was evaluated in different secondary acute myeloid leukemia models and showed potent efficacy in inhibition of acute myeloid leukemia (AML) LSC and disruption of AML maintenance in vitro and in mouse xenograft models (Crews et al. 2016). The study by Crews et al. indicates the pivotal role of spliceosome in secondary acute myeloid leukemia and the therapeutic potential of targeting leukemia stem cells in this subtype of AML often unresponsive to current therapy.

Xanthene-Based Dyes For Voltage Imaging

Rapid changes in the membrane potential of excitable cells (e.g., neurons and cardiomyocytes) play a central role in defining the cellular signaling and physiological profiles of these specialized cells. Typically, the membrane potential is monitored and measured via patch clamp electrophysiology, which involves the use of a micro-electrode attached to or near the cell of interests.  Unfortunately, the use of an electrode is highly invasive, limits records to the soma of a single cell and is extremely low throughput. Researchers at the University of California, Berkeley have designed and synthesized a voltage sensitive indicator that can provide excitation and emission profiles greater than 700 nm, and as such, represents an important method for visualizing membrane potential in living cells.

Modulation Of p53 as a Cancer Therapeutic Target

Researchers at the University of California, Davis have designed peptides and oligonucleotide sequences to enhance p53 expression.

Biologically Applicable Water-Soluble Heterogeneous Catalysts For Parahydrogen-Induced Polarization

UCLA researchers in the Department of Chemistry and Biochemistry have developed a novel method of parahydrogen-induced polarization in water using heterogeneous catalysts.

Determination Of Absolute Configuration Of Secondary Alcohols Using A Competing Enantioselective Conversion Kit

The absolute configuration of an organic compound dictates its interactions with other chemicals. The Competing Enantioselective Conversion (CEC) method is an attractive method for determining the absolute configuration of secondary alcohols, but the preparation of stock reagent solutions takes longer than the analysis time itself – a mere 1-2 hours. The inventors at UCI have developed a CEC kit which contains stock solutions of the components required for CEC that remain stable and usable for several months.

Sieve Container For Contactless Media Exchange For Cell Growth

Media that contains nutrients and growth factors is necessary to grow all types of cells, a process that is widely used in many fields of research. Such media should be routinely changed either to different media or a fresh batch of the same media. This change currently involves either using a pipette to transfer cells from their current dish of media to a new dish, or aspirating the media out of the dish and replacing it with new media. Both methods have inherent risks to stressing and damaging the cells. Researchers at UCI have developed a unique dish for growing cells that allows for safer aspiration of the old media, which reduces stress and damage to the cells.

Gene Delivery Into Mature Plants Using Carbon Nanotubes

96 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} Current methods of biomolecule delivery to mature plants are limited due to the presence of plant cell wall, and are additionally hampered by low transfection efficiency, high toxicity of the transfection material, and host range limitation. For this reason, transfection is often limited to protoplast cultures where the cell wall is removed, and not to the mature whole plant.  Unfortunately, protoplasts are not able to regenerate into fertile plants, causing these methods to have low practical applicability. Researchers at the University of California have developed a method for delivery of genetic materials into mature plant cells within a fully-developed mature plant leaf, that is species-independent. This method utilizes a nano-sized delivery vehicle for targeted and passive transport of biomolecules into mature plants of any plant species. The delivery method is inexpensive, easy, and robust, and can transfer biomolecules into all phenotypes of any plant species with high efficiency and low toxicity.

Xenobiotic-Free Culture System To Expand Human Limbal Stem Cells

UCLA researchers in the Departments of Opthalmology have developed a xenobiotic-free manufacturing process to produce transplantable human limbal stem cells for use in treating limbal stem cell deficiency.

Au(III) Complexes For [18F] Trifluoromethylation

96 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} The biological properties of trifluoromethyl compounds (e.g, CF3) have led to their ubiquity in pharmaceuticals, yet their chemical properties have made their preparation a substantial challenge, necessitating innovative chemical solutions.  For example, strong, non-interacting C-F bonds lend metabolic stability while simultaneously limiting the ability of chemical transformations to forge the relevant linkages and install the CF3 unit.  When these same synthetic considerations are extended toward the synthesis of trifluoromethylated positron emission tomography (PET) tracers, the situation becomes more complex.   UC Berkeley researchers discovered an unusual alternative mechanism, in which borane abstracts fluoride from the CF3 group in a gold complex. The activated CF2 fragment can then bond to a wide variety of other carbon substituents added to the same gold center. Return of the fluoride liberates a trifluoromethylated compound from the metal. This mechanism would be useful for the introduction of radioactive fluoride substituents for potential tracers to be used for positron emission tomography applications.

Next-generation broad-spectrum anti-cancer Rad51 inhibitors

This invention describes the design, synthesis and successful evaluation of a panel of novel Rad51 inhibitors to treat a broad spectrum of cancer types.

Small Molecule Generation of Multinucleated and Striated Myofibers from Human Pluripotent Stem Cells Equivalent to Adult Skeletal Muscle

Researchers in the UCLA Department of Microbiology, Immunology and Molecular Genetics have developed a novel means of generating adult skeletal muscle-equivalent myofibers from human pluripotent stem cells.

Siderophore-Based Immunization Against Gram-Negative Bacteria

Bacterial pathogens such as E. coli and Salmonella hijack the host’s iron to cause infection. This invention describes an immunization strategy for triggering an immune response against the iron-sequestering agent secreted by the pathogen, thus turning the bacterial virulence mechanism against itself, and thereby resulting in host immunity.

Improved Cell-Free Protein Synthesis For Protein Microarray

Researchers at UC Irvine have developed a cell-free (CF) protein synthesis system to solubilize and synthesize highly hydrophobic membrane proteins that would typically aggregate using current CF synthesis systems. With such high amounts of synthesized proteins, researchers intend to build protein microarrays for diagnostic purposes.

Antibodies targeting mammalian Sterol Regulatory Element Binding Proteins (SREBP) 1 and 2

Sterol Regulatory Element Binding Proteins (SREBP) are important factors that control lipid homeostasis in mammals. Researchers at UCI have prepared antibodies that have good affinity and specificity for human SREBP1/2 for use as research tools. These antibodies have application in genetic and immunotherapeutic research areas.

Rapid And Selective Cycloaddition Reaction For Applications In Molecular Imaging

UCLA researchers in the Department of Molecular and Medical Pharmacology, and Department of Chemistry and Biochemistry have designed a new reaction with 18F-chemistry platform, allowing a highly selective, efficient and rapid approach to label biomolecules with a chemical reporter (i.e. radionuclide, fluorescent dye) for molecular imaging.

Voltage-Sensitive Dyes In Living Cells

96 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:Calibri; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} Comprehensively mapping and recording the electrical inputs and outputs of multiple neurons simultaneously with cellular spatial resolution and millisecond time resolution remains an outstanding challenge in the field of neurobiology. Traditionally, electrophysiology is used to directly measure membrane potential changes. While this technique yields sensitive results, it is invasive and only permits single-cell recording.  VoltageFluor dyes rely on photoinduced electron transfer to effectively report membrane potential changes in cells. This approach allows for fast, sensitive and non-invasive recording of neuronal activity in cultured mammalian neurons and in ex-vivo tissue slices. However, one major limitation of small-molecule dye imaging is the inability to target the dye to specific cells of interest.   UC Berkeley researchers have developed latent voltage sensitive dyes that require a fluorogenic activation step. This new class of VoltageFluor dyes are only weakly fluorescent until being activated in defined cell types via biological processes. In particular, the VoltageFluor dyes described herein comprise a bioreversible group that quenches the fluorescence of the VoltageFluor dye, that upon selective removal by the action of biological processes (e.g., enzymes) thereby activates the fluorescence of the VoltageFluor dye. The researchers found that the new dye facilitated the observation of spontaneous activity in rat hippocampal neurons.  

Preventing Protein Aggregation using Thermal Protectants

Protein aggregation in the brain are the causes of the neurodegenerative diseases Alzheimer’s and Parkinson’s. To study diseases and cellular mechanisms, biologists need to be able to efficiently synthesize, isolate and purify proteins. The invention herein is a synthetic nanoparticle (NP) that protects proteins from aggregation at temperatures, which normally cause aggregation. Furthermore, multiple stimuli can release the protein in high yield from the NPs.

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