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Novel Method to Identify Unknown Viruses

Prof. Shou-wei Ding and colleagues at UCR have developed a new method for virus discovery that is independent of either amplification or purification of viral particles. Virus-derived siRNAs and piRNAs are produced by the host immune system as an antiviral response to viral infection. These viral siRNAs and piRNAs are overlapping in sequence and can be assembled back into long continuous fragments of the infecting viral RNA genome. A researcher may sequence the total small RNAs of 18 to 29 nucleotides in length in a disease sample and search a public database of viral sequences using the contiguous sequences assembled from the small RNAs to identify a new or known virus with homology to all or part of a known viral genome in the database.

Novel Assay to Screen for Antiviral Therapeutics

Prof. Shou-wei Ding and colleagues at UCR have developed three different assays to screen for a new class of antiviral therapies. RNA interference (RNAi) directs antiviral innate immunity by producing virus-derived siRNAs (vsiRNAs). These assays screen for compounds that may be used to inhibit the activity of a distinct group of viral proteins known as viral suppressors of RNAi (VSRs) essential for virus infection. The various assays may use Drosophila, rodent or human somatic cells. These same assays may also be used to identify new VSRs.    

Potent And Highly Soluble Pegylated Compstatin Peptide

UCR researchers have developed novel compstatin peptides with polar amino acid extensions at the N-terminus and PEGylated extensions at the C-terminus. The new peptides have the following advantages compared to previously known compstatin peptides: (i) highly improved aqueous solubility while maintaining high inhibitory potency, and (ii) higher inhibitory efficacy against complement system activation in a human retinal pigmented epithelial cell-based assay that mimics the pathobiology of age-related macular degeneration. The combined solubility and inhibitory potency and efficacy properties render the new peptides excellent candidates to become therapeutics for the treatment of age-related macular degeneration.   A potent and highly soluble compstatin peptide shown in surface representation with an 8 PEG block C-terminal extension displayed in stick form. The surface of the compstatin analog is colored according to amino acid properties: gray for hydrophobic, green for polar neutral, blue for polar positively charged, red for polar negatively charged, yellow for cysteines of the disulfide bridge, and brown for glycine. The molecular image is generated using three-dimensional coordinates from a molecular dynamics simulation trajectory.    

Peptides for Enhanced Intranasal Vaccination

Brief description not available

Splice Modulating Oligonucleotides as a Breast Cancer Therapy

UCR researchers have designed novel splice modulating oligonucleotides (SMOs) that decrease expression of the long form of the prolactin receptor, thereby significantly inhibiting the metastatic spread of breast cancer to the lungs and liver. The SMO treatment also increased central death in the primary breast tumor. These SMOs may also target metastases produced by non-prolactin receptor-expressing primary tumors since all cancer stem cells examined so far are positive for the prolactin receptor. The researchers administered SMOs to two highly aggressive metastatic models of breast cancer, BT474 human xenografts, used for testing Herceptin, and a 4T1 syngeneic mouse model, which allows testing with an intact immune system.   Fig. A shows a reduction in the number of metastatic colonies upon treatment with the UCR SMOs.       Fig. B titled "Control" is a stain of the metastatic colonies without SMO treatment. Fig. B titled "PRLR SMO" is a stain of the colonies after 40 days treatment with the UCR SMOs.

C3d-binding Biomarkers for Detection of Complement-mediated Inflammation

Background: The complement immune system is implicated in many acute and chronic inflammatory conditions and autoimmune diseases, including neurological (Alzheimer’s and multiple sclerosis), renal (lupus nephritis and glomerulonephritis), ocular (age-related macular degeneration), and systemic (lupus and rheumatoid arthritis). The complement protein C3d resides covalently attached in inflamed tissues, and it is an excellent biomarker target for complement-mediated inflammation, even at early disease stages prior to clinical manifestations.  Brief Description: UCR researchers have discovered several small chemical compounds with intrinsic fluorescence properties that bind to complement C3d. These compounds can serve as molecular biomarkers for the detection of complement activation using fluorescence imaging. The compounds can be developed to become noninvasive in vivo diagnostics of complement-mediated inflammatory and autoimmune diseases, for spatiotemporal monitoring of disease progression, and for delivering therapeutics to sites of inflammation.

Hydrogel for Improved Burn Wound Healing

Background: The US spends $25B alone on wound treatment of burns. The wound treatment market is projected to grow to $18.3B in just 4 years. Current treatments have been unsuccessful in fostering proper wound healing safe from infections. Not only do they have low efficacy, but they are very expensive to produce. The most commonly used wound dressing is a hydrogel. Hydrogels reduce pain and healing time, promotes cell proliferation and collagen deposition, and is the most appropriate for burn wounds.  Brief Description: UCR researchers have developed a novel formulation that can be embedded into a hydrogel to significantly improve wound healing. Through successful conjugation of a peptide and polymer, stability and longevity have been enhanced. Their formulation induced a 3-fold increase in density of newly formed microvessels, greatly improving tissue quality.

A Method to Reduce the Toxicity of 3D-Printed Parts

Despite the rapid growth of 3DP industry and widespread acceptance of 3D-printed products among consumers, little has so far been done on assessing the toxicity of those products. In this technology, UCR scientists first revealed the dangerous effects of STL- (and to a lesser extent FDM-) printed parts on zebrafish embryos and then developed an easy-to-implement, industry-friendly protocol for the detoxification of 3D-printed products using UV light.

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