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FLUORESCENCE-BASED REPORTERS FOR MUTAGENESIS DETECTION IN E. COLI

When model organisms are exposed to chemicals, resulting mutagenesis can provide insights on the chemical’s genotoxicity, which is an indicator of the chemical’s potential to cause cancer or birth defects. In fact, direct mutagenesis assays in bacteria are one of the three assays required by regulatory agencies for demonstrating the safety of potential clinical compounds. Mutagenesis assays are also used to study various DNA processes, such as replication, repair, damage tolerization, and homeostasis.

System For Continuous Mutagenesis In Vivo To Facilitate Directed Evolution

This invention overcomes a limitation of in vivo mutagenesis systems. Some methods of mutagenesis involve treatment of plasmids with mutagenic chemicals or UV light prior to transformation, but these result in biased mutation spectra. Use of error prone DNA polymerases produces a more random set of mutations, but the rate of mutagenesis rapidly declines with continuous culture. As a result, using such polymerasaes separates mutagenesis and selection into multiple steps. Mutant genes in plasmids need to be generated by the error prone polymerase, then the plasmids isolated into libraries and selected in a separate step. What is needed, then is an error prone DNA polymerase that does not result in a decline in the rate of mutagenesis in culture.  

Epigenetic Prevention and Treatment of CDKL5 Deficiency Disorder

Researchers at the University of California, Davis have developed a targeted epigenetic approach for the prevention and treatment CDKL5 deficiency disorder.

(SD2020-266) Protein Domains For Modulation Of Rna Stability And/Or Translation

Existing art in modulation of gene expression by nucleic acid targeting mechanisms primarily comprises methods for REDUCING gene expression, e.g. via DNA targeting (CRISPR gene knockout, reduction of transcription via CRISPR-i), or RNA targeting (shRNAs/siRNAs, ASOs, microRNA mimics). ENHANCEMENT of gene expression on the RNA level has been achieved using microRNA inhibitors; however the effects are typically small and are not target-specific (many other microRNA target-RNAs are also upregulated).The molecular functions of the majority of RNA-binding proteins (RBPs) remain unclear, highlighting a major bottleneck to a full understanding of gene expression regulation. 

(SD2022-045) RUBY Plasmids: A reporter for noninvasively monitoring gene expression and plant transformation

Researchers at UC San Diego in collaboration with others have constructed a new reporter RUBY that converts tyrosine to vividly red betalain, which is clearly visible to naked eyes without the need of using special equipment or chemical treatments. They demonstrated that RUBY can be used to noninvasively monitor gene expression in plants. Furthermore, they show that RUBY is an effective selection marker for transformation events.Reporters have been widely used to visualize gene expression, protein localization, and other cellular activities, but the commonly used reporters require special equipment, expensive chemicals, or invasive treatments.

One-Pot Multienzyme Synthesis of Sialidase Reagents, Probes and Inhibitors

Researchers at the University of California, Davis, have developed an environmentally friendly one-pot multienzyme (OPME) method for synthesizing sialidase reagents, probes, and inhibitors.

In plantae production of heterologous proteins using viral amplicons

Researchers at the University of California, Davis have developed a viral amplicon-based vector system for heterologous protein expression and production in plants.

New Bright Green Fluorescent Proteins

Fluorescent proteins (FP) have been widely used as research tools in both academia and pharma for many years.  Naturally occurring FP have been mutated to either be brighter, be monomers, and/or for easier folding and expression in cells.  The most common FP to date has been the green fluorescent protein (GFP) of the jelly fish Aequorea victoria which can be expressed in cells and fused with proteins of interest, and has proven to be an excellent tool to study protein localization, expression, signaling, etc. in real time via microscopy and other techniques. 

Temporal Control over DNA-Patterned Signaling Ligands In Vitro Using Sequence-Targeting Nucleases

UC Berkeley researchers have created a new technique that can rapidly “print” two-dimensional arrays of cells and proteins that mimic a wide variety of cellular environments in the body, be it the brain tissue surrounding a neural stem cell, the lining of the intestine or liver or the cellular configuration inside a tumor.  In the new technique, each cell or protein is tethered to a substrate with a short string of DNA. While similar methods have been developed that attach tethered cells or proteins one by one.  By repeating the process, up to 10 different kinds of cells or proteins can be tethered to the surface in an arbitrary pattern. This technique could help scientists develop a better understanding of the complex cell-to-cell messaging that dictates a cell’s final fate, from neural stem cell differentiating into a brain cell to a tumor cell with the potential to metastasize to an embryonic stem cell becoming an organ cell.

Novel Non-Immunogenic Positron Emission Tomography Gene Reporter

UCLA researchers in the Department of Pharmacology and Department of Microbiology, Immunology, & Molecular Genetics have developed a novel positron emission tomography reporter gene to preferentially trap radiolabeled deoxycytidine analogs.

Non-Immunogenic Positron Emission Tomography Gene Reporter Systems

UCLA researchers in the Department of Pharmacology and Department of Microbiology, Immunology, & Molecular Genetics have developed a novel dual gene positron emission tomography reporter system for the enhanced labeling of cells in vitro and in vivo.

DARTS: Deep Learning Augmented RNA-seq Analysis of Transcript Splicing

Researchers led by Yi Xing have developed a novel deep learning algorithm to detect alternative splicing patterns in RNA-seq data

Sustained Intracellular RNA Delivery and Expression

UCLA researchers in the Department of Chemistry and Biochemistry have developed a novel method for high protein expression levels, in situ, involving RNA-based therapeutics.

Method to Direct the Reciprocal Interactions Between the Ureteric Bud and the Metanephric Mesenchyme

Researchers at UCLA have developed an approach to construct an embryonic kidney in vitro for the treatment of end stage renal disease.

Simultaneous Detection Of Protein Isoforms And Nucleic Acids From Low Starting Cell Numbers

Embryo-specific nucleic acid modifications, including retrotransposon activity-derived genomic modifications and alternative splicing of mRNA, is crucial for the development of mammalian embryos. However, determining if all genomic modifications and mRNA isoforms translate to protein variations remain intriguing questions due to difficulty in measuring protein isoforms and nucleic acids from small starting cell numbers.    UC Researchers have developed a system for performing dual nucleic acid and protein isoform measurements on low starting cell numbers equivalent to the number of blastomeres composing early embryonic development stages (morula and blastocysts).  The system integrates fractionation polyacrylamide gel electrophoresis (fPAGE) with off-chip analysis of nucleic acids in the nuclei. An additional method can be used to remove nuclei for off-chip analysis. The system can measure expression of protein isoforms from the cytoplasmic fraction of 1-100 cells while achieving analysis of either DNA or mRNA retained in the nuclei. The researchers have demonstrated signal from immunoprobed protein correlates strongly with protein expression prior to lysis in TurboGFP-expressing cells and that mRNA levels correlate with protein abundance in TurboGFP-expressing cells.

Synthetic Algal Promoters as a Tool for Increasing Nuclear Gene Expression in Green Algae

Algae have enormous potential as bio-factories for the efficient production of a wide array of high-value products, and eventually as a source of renewable biofuels. However, tools for engineering the nuclear genomes of algae remain scarce and limited in functionality, in part due to lack of strong promoters.

A Cell-Based Seeding Assay for Huntingtin Aggregation

UCLA researchers from the Department of Psychiatry has created a novel cell-based seeding assay for sensitive, specific and high throughput detection of mutant Huntingtin proteins in biological samples.

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.

High-Throughput Intracellular Delivery of Biomolecular Cargos via Vibrational Cell Deformability within Microchannels

UCLA Researchers in the Departments of Chemistry and Materials Science & Engineering have developed a novel means of delivering intracellular cargo.

Bioorthogonally-Engineered Extracellular Vesicles for Applications in Detection and Therapeutic Delivery

Extracellular vesicles (EVs) are promising as drug delivery carriers because they are inherently biocompatible, It would be desirable to efficiently, specifically, and rapidly change the EVs surface presentation to program the interactions with its target cells. Inventors at UC Irvine have developed a strategy for functionalizing the cellular membranes of EVs with precision and ease.

New label-free method for direct RNase activity detection in biological samples

Researchers at the University of California, Davis have developed a new and simple, label-free method to detect milligram levels of RNase activity in undiluted biological samples that is selective, accurate and scalable.

Transposon Vector for Vertebrate & Invertebrate Genetic Manipulation

Background: Therapeutic delivery of genes is a rapidly evolving technique used to treat or prevent a disease at the root of the problem. The global transgenic market is currently $24B, growing at an annual projected rate of 10%. Currently, a variation of this technique is widely used on animals and crops for production of desirable proteins, but this is a heavily infiltrated market. Thus, entering the gene therapy segment is more promising and would enhance the growth of this industry.  Brief Description: UCR Researchers have identified a novel transposon from Aedes aegypti mosquitoes. This mobile DNA sequence can insert itself into various functional genes to either cause or reverse mutations. They have successfully developed a transposon vector system that can be used in both unicellular & multicellular organisms, which can offer notable insight to improve current transgenic technologies as well as methods of gene therapy.

Dielectrophoresis-Based Cell Destruction to Eliminate/Remove Unwanted Subpopulations of Cells

This invention allows for label free cell separations and cell enrichment.

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