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Nanowire Building Block

Nanowires have applications as transistors or bioelectronic devices. Current methods to synthesize nanowires lack the ability to precisely control length, sequence, and terminal functionality. Using this invention as a building block, organic nanowires can be made with controlled length, sequence, and terminal functionality. The organic nanowires made with this invention also exhibit zero-resistance and do not degrade with increased length.

Soluble Fluorescent DNA Label

Assays or biosensors that utilize electrochemical or fluorescent techniques often employ DNA electrochemical probes. Current probes have drawbacks, as they have either electronic or fluorescent properties, are not readily water-soluble, and are poorly coupled within a DNA strand. This invention is a DNA electrochemical probe that has both electronic and fluorescent properties, is water-soluble, and can readily incorporate into a DNA strand.

DNA Amplification by Electric Field Cycling (efc-PCR)

Polymerase Chain Reaction (PCR) is a popular technique for amplifying and quantifying minute quantities of DNA. Technologies based on PCR are used for a wide range of applications, including forensics, disease detection, and laboratory tools. Researchers at UCI have developed a device that can implement a novel method for PCR based on voltage cycling as opposed to temperature cycling (the current method for PCR). This allows the device to be much more portable and compact than those currently available.

Therapeutic strategies for Huntington’s Disease using stop codon suppression

In Huntington’s Disease (HD), aberrant splicing of the huntingtin protein can produce a highly toxic peptide that accumulates in the brain. The invention describes methods to minimize the toxicity of spliced proteins.

Enhanced Cell/Bead Encapsulation Via Acoustic Focusing

The invention consists of a multi-channel, droplet-generating microfluidic device with a strategically placed feature. The feature vibrates in order to counteract particle-trapping micro-vortices formed in the device. Counteracting these vortices allows for single particle encapsulation in the droplets formed by the device and makes this technology a good candidate for use in single cell diagnostics and drug delivery systems.

Aptamers that promote neuronal growth by binding to and blocking the protein Nogo

Neuronal growth inhibiting protein (Nogo), blocks regrowth of damaged neuronal projections (axons) in neurodegenerative disorders. Currently, researchers are developing antibody proteins to inhibit Nogo and produce axon regrowth in a variety of disorders. However, such antibodies are unstable and costly to synthesize. At UCI, the synthesis of nucleic acid molecules called aptamers that selectively bind and block Nogo to promote axonal growth presents a promising alternative pharmaceutical target for treating a range of disorders including spinal cord injury, stroke, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS).

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

An Integrated Microfluidic Platform For Selective Extraction Of Single-Cell mRNA

The invention is a high-density, single-cell trapping array. A specialized probe tip can be precisely manipulated to non-destructively collect targeted intracellular material from the trapped cells for measurements. Due to the non-destructive nature of the invention, the integrity and function of the trapped cells can be preserved and they can be monitored over time to better understand disease processes.

Novel Method for Finding Low Abundance Sequences By Hybridization

This invention describes a novel method for enriching rare sequences in nucleic acid libraries.

A non-destructive method of quantifying mRNA in a single living cell

The detection of levels of messenger RNA (mRNA), the molecule used by DNA to convey information about protein production, is a very important method in molecular biology. Current detection strategies, such as Northern Blotting and RT-PCR, require destruction of the cell to extract such information. Researchers at the University of California, Irvine have developed a method to non-destructively assess mRNA levels in a single living cell.

Directed Evolution Of AAV Vectors That Undergo Retrograde Axonal Transport

Brain functions such as perception, cognition, and the control of movement depend on the coordinated action of large-scale neuronal networks, which are composed of local circuit modules that are linked together by long-range connections.  Such long­ range connections are formed by specialized projection neurons that often comprise several intermingled classes, each projecting to a different downstream target within the network. Projection neurons have also been implicated in the spread of several neurodegenerative diseases. Selective targeting of projection neurons for transgene delivery is important both for gaining insights into brain function and for therapeutic intervention in neurodegenerative diseases.   Viral vectors constitute an important class of tools for introducing transgenes into specific neuronal populations, but their potential for biological investigation and gene therapy is hampered by excessive virulence.  Other viruses can infect neurons when administered directly to the nervous system, with "pseudorabies", adenoviruses and lentiviruses used most commonly in animal research. However, these viruses mediate only modest levels of transgene expression, have potential for toxicity, and are currently not easily scalable for clinical or large animal studies.  Recombinant adeno-associated viruses (rAAVs) are an effective platform for in vivo gene therapy, as they mediate high-level transgene expression, are non-toxic, and evoke minimal immune responses.  rAAVs have allowed retrograde access to projection neurons, but their natural propensity for retrograde transport is low, hampering efforts to address the role of projection neurons in circuit computations or disease progression.    UCB and HHMI researchers have produced a new rAAV variant (rAAV2-retro) that permits robust retrograde access to projection neurons with efficiency comparable to classical synthetic retrograde labeling reagents.  The rAAV2-retro gene delivery system can be used on its own or in conjunction with Cre recombinase driver lines to achieve long-term, high-level transgene expression that is sufficient for effective functional interrogation of neural circuit function, as well as for CRISPR/Cas9-mediated and other genome editing in targeted neuronal populations.  As such, this designer variant of adeno-associated virus allows for efficient mapping, monitoring, and manipulation of projection neurons.

C2c2 - A Dual Function Programmable RNA Endoribonuclease

Bacterial adaptive immune systems employ CRISPRs and CRISPR-associated (Cas) proteins for RNA-guided nucleic acid cleavage. Although generally targeted to DNA substrates, the Type VI CRISPR system directs interference complexes against single-stranded RNA substrates and in Type VI CRISPR systems, the single-subunit C2c2 protein functions as an RNA-guided RNA endonuclease.   UC Berkeley researchers have discovered that the CRISPR-C2c2 has two distinct RNase activities that enable both single stranded target RNA detection and multiplexed guide-RNA processing.  These dual RNase functions were found to be chemically and mechanistically different from each other and from the CRISPR RNA processing behavior of the evolutionarily unrelated CRISPR enzyme Cpf1.  Methods for detecting the single stranded target RNA were also discovered using a C2c2 guide RNA and a C2c2 protein in a sample have a plurality of RNAs as well as methods of cleaving a precursor C2c2 guide RNA into two or more C2c2 guide RNAs.  

Versatile Cas9-Mediated Integration Technology

Many advancements to the Cas9 system (both the Cas9 nuclease and the sgRNA sequence) have been made to increase and optimize its efficiency and specificity.  Since many diseases and traits in humans have a complex genetic basis, multiple genomic targets must be simultaneously edited in order for diseases to be cured or for traits to be impacted.  Thus in order for CRISPR/Cas9 to be an effective gene therapeutic technology, huge swathes of the genome must be edited simultaneously, efficiently, and accurately. To address many of these issues, UC Berkeley researchers have developed a system method to rapidly manipulate multiple loci. This system allows for either sequential (maintaining inducible Cas9 present in the genome) or simultaneous (scarless excision) manipulation of Cas9 itself and can be applied to any organism currently utilizing the CRISPR technology.  The system can also be applied conveniently to create genomic libraries, artificial genome sequences, and highly programmable strains or cell lines that can be rapidly (and repeatedly) manipulated at multiple loci with extremely high efficiency.  

Pyrite Shrink-Wrap Laminate As A Hydroxyl Radical Generator

The invention is a diagnostic technology, as well as a research and development tool. It is a simple, easy to operate, and effective platform for the analysis of pharmaceuticals and biological species. Specifically, this platform generates hydroxyl radicals for oxidative footprinting – a technique commonly employed in protein mapping and analysis. The platform itself is inexpenisve to fabricate, scalable, and requires nothing more than an ordinary pipet to use. In addition, it is highly amenable to scale-up, multiplexing, and automation, and so it holds promise as a high-throughput method for mapping protein structure in support of product development, validation, and regulatory approval in the protein-based therapeutics industry.

CRISPR genome editing of Zygotes (CRISPR-EZ)

0 0 1 214 1224 UC Berkeley 10 2 1436 14.0 Normal 0 false false false EN-US JA 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:Cambria; mso-ascii-font-family:Cambria; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Cambria; mso-hansi-theme-font:minor-latin;} Easily accessible and efficient methodologies to edit the genomes of organisms are an immense resource to the biological and biomedical research community. Traditionally, engineering of the mammalian genome is achieved by homologous recombination (HR)-mediated sequence substitution in embryonic stem cells (ESCs), a time consuming process that occurs at low frequency. Taking genetically engineering in mice for example, after extensive screening for ESC colonies with the desired genetic modifications, ESCs are microinjected into mouse blastocysts to generate chimeras capable of germline transmission. Such chimera mice are then crossed to wild-type mice to generate heterozygous offspring (F1), which are then intercrossed to yield homozygous mutant mice (F2) that can be subjected to phenotypic analyses. Despite the wide use of this technology to generate transgenic mice, the low efficiency of HR in ESCs, the laborious process of screening, the technical difficulty of microinjection, and the nature of the mouse life cycle make this approach a lengthy and costly process.   UC Berkeley researchers developed methods for modifying the genome of a mammalian zygote by introducing a ribonucleoprotein complex (RNP) to the zygote via electroporation.  Suitable genome editing nucleases were found to be CRISPR/Cas endonucleases (e.g., class 2 CRISPR/Cas endonucleases such as a type II, type V, or type VI CRISPR/Cas endonucleases.  

Fluorescent Biosensor for Cyclic GMP-AMP (cGAMP)

The cGAS-cGAMP-STING pathway is an important immune surveillance pathway which gets activated in presence of cytoplasmic DNA either due to a microbial infection or a patho-physiological condition, including cancer and autoimmune disorders. Sensing 2’3’ cGAMP level is important in diagnostics perspective as well as in basic understanding of their regulation.  Small molecule activators of this pathway have also been shown to activate an anti-cancer immune response and thus an important use for pharmaceutical applications. However, a high throughput method to screen for such potential drugs is still not available. UC Berkeley researchers have designed a RNA-based fluorescent biosensor for directly detecting 2’3’ cGAMP. The biosensor was able to detect 2’3’ cGAMP and assay cGAS activity in vitro and thus would be useful for high throughput screening of small molecule modulators of cGAS activity.  The biosensor was sensitive enough to quantify 2’3’ cGAMP in dsDNA- stimulated mammalian cell extracts. 

Enzymatic Site Specific Labeling of RNA with Unnatural Nucleobases

The detection and manipulation of RNA is greatly aided by chemical modification. Therefore, there is tremendous interest in novel methods to site-specifically associate RNA with small molecules such as imaging probes and affinity labels.  Conventional methodologies for detecting RNA include the use of antisense probes, aptamers, and fusion proteins that recognize specific RNA secondary structures. Relatively less explored are the use of enzymatic reactions for site-specific RNA labeling. Notably, these past approaches have not demonstrated the ability to append large functional molecules directly onto the RNA of interest. Instead they typically rely upon small bio-orthogonal handles, which after undergoing a second chemical reaction, can be modified by functional probes such as fluorophores or affinity ligands. An ideal enzymatic reaction for labeling RNA would involve recognition of a minimal RNA structural motif, result in irreversible covalent modification, and would be capable of directly incorporating a diverse array of functional molecules such as fluorophores, affinity ligands, etc. in a single step.

Sequence Independent and Ordered Nucleic Acid Assembly

Currently DNA fragments are assembled from smaller oligonucleotides that contain overlapping DNA sequences.After overlapping sequences are annealed, each oligo will act as primer for polymerization, eventually fusing the two fragments together. This method relies on unique overlapping sequences that are favorable to anneal at a specific temperature.This strategy becomes problematic when you try to assemble more than two fragments, when the uniqueness of annealing sequences, the correct order of fragments annealing and optimal temperature for all the annealing reactions are major concerns.On the other hand, annealing only two fragments at a time is time consuming and low in scalability.There is a great need for a cost-effective and accurate approach.

High Throughput, Sequence Independent and Ordered Nucleic Acid Assembly

Currently DNA fragments are assembled from smaller oligonucleotides that contain overlapping DNA sequences.  After overlapping sequences are annealed, each oligo will act as primer for polymerization, eventually fusing the two fragments together.  This method relies on unique overlapping sequences that are favorable to anneal at a specific temperature.  This strategy becomes problematic when you try to assemble more than two fragments, when the uniqueness of annealing sequences, the correct order of fragments annealing and optimal temperature for all the annealing reactions are major concerns.  On the other hand, annealing only two fragments at a time is time consuming and low in scalability.  There is a great need for a cost-effective and accurate approach.


This invention identifies a method to prepare nucleic acid barcodes using microfluidic methods; allowing for high throughput analysis of many individual samples.

Small RNAs From Fungal Pathogents Act As Effector Molecules To Suppress Host Immunity

Background: Plant-pathogen relationships have been studied meticulously for many years because fungi are notorious for causing detrimental yield losses. Many have taken a biotechnological approach to combatting fungal infections by genetically engineering fungal-resistant genes into plants. The market segment of genomic-enabled products is projected to grow 10% annually and reach $38.6B by 2019.    Brief Description: UCR Researchers have discovered the underlying mechanism of action of Botrytis cinerea, a fungal pathogen that causes grey mold disease in various plants and crops. They’ve identified novel non-protein effectors, small RNAs, that silence specific genes in the host. These fungal sRNAs are transferred into the host cells to suppress its immunity and achieve full infection. With this insight, we can genetically engineer plants to successfully combat harmful pathogenic attacks by inhibiting small RNA effectors.  

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.

Multiplex Digital PCR

Researchers at the University of California, Irvine have developed methods to enable greater multiplexing abilities for digital polymerase chain reaction (PCR) so that up to 100 genetic targets may be analyzed. In the past multiplexing of digital PCR samples has been limited to only one probe per color. However multiple probes may be labeled by using combinatorial encoding of color, exploiting reaction rates of PCR cycles and modulating the intensity of Taqman and/or intercalating dyes therefore allowing a greater number of probes to be labeled.

Real-Time, Label-Free Detection of Nucleic Acid Amplification in Droplets Using Impedance Spectroscopy and using Solid-Phase Substrates

Researchers at UC Irvine have developed a technology to detect the presence of nucleic acid amplification in a droplet. This technology yields real time detection of DNA or RNA amplication in a high throughput integrated microfluidic platform.

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