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Novel Inhibitors of Mitochondrial Electron Transport

Researchers at the University of California, Davis have discovered a class of compounds that both bind to a unique newly-discovered binding site in respiratory complex III and act as inhibitors of electron transport for use as mitochondrial anti-cancer drugs.

Methods for Global RNA-Chromatin Interactome Discovery

Recent decades of genomic research reveal that mammalian genomes are more prevalently transcribed than previously anticipated. It is now quite clear that mammalian genomes express not only protein-coding RNAs but also a large repertoire of non-coding RNAs that have regulatory functions in different layers of gene expression. Many of those regulatory RNAs appear to directly act on chromatin, as exemplified by various long noncoding RNAs (IncRNAs). Some of those regulatory RNAs mediate genomic interactions only in cis, while others, such MALAT1 and NEAT1, are capable of acting in trans. These findings suggest an emerging paradigm in regulated gene expression via specific RNA-chromatin interactions. Various techniques have been developed to localize specific RNAs on chromatin. These methods, such as chromatin Isolation by RNA purification or comprehensive identification of RNA binding proteins (ChIRP), capture hybridization analysis of RNA targets (CHART), and RNA affinity purification (RAP), all rely on using complementary sequences to capture a specific RNA followed by deep sequencing to identify targets on chromatin. Importantly, all of these methods only allow analysis of one known RNA at a time, and up to date, a global view is lacking on all RNA-chromatin interactions, which is critical to address a wide range of functional genomics questions.

Diagnostic Gene Signature For Cancer Vascular Mimicry in Solid Tumors

One of the characteristic trademarks of tumorigenesis is the need for an extensive vascular system to supply blood for the tumor to grow and disseminate from the original node to distant sites via the process of metastasis. This involves the growth of new vessels from existing vessels, as well as the migration of tumor cells through the extracellular matrix (ECM) and into the lymphatic or vascular systems. However, some very aggressive solid tumors can form vascular channels by themselves, which is termed vascular mimicry (VM). Moreover, only certain cells in these tumors have the ability to produce blood-transporting channels, contributing to metastasis. There is growing evidence that supports the idea that VM can be a prognostic factor for poor clinical outcomes in various types of cancer. Currently, VM is identified by a pathologist’s evaluation of histological slides, wherein vascular-like structures that do not stain positive for endothelial cells are identified as VM. Thus far, conserved molecular biomarkers that define this phenotype have remained unknown.

Assay for Inhibitors of Nonsense-Mediated RNA Decay

Prof. Sika Zheng at UCR has developed a new endogenous NMD assay that is both sensitive and quantitative. The assay can be used on its own to assess changes in cellular NMD activity with high specificity and sensitivity. It can facilitate analysis of NMD controls by cellular pathways in response to stimuli or during development and is particularly suitable for unbiased screening of NMD modulators. The assay is designed to distinguish NMD regulation from transcriptional regulation and alternative splicing control.

Drop-Carrier Particles For Digital Assays

UCLA researchers in the Department of Bioengineering have developed a novel drop-carrier particle for single cell or single molecule assays.

Low Cost Wireless Spirometer Using Acoustic Modulation

The present invention relates to portable Spirometry system that uses sound to transmit pulmonary airflow information to a receiver.

Microfluidic Component Package

The present invention describes a component package that enables a microfluidic device to be fixed to a Printed Circuit Board (PCB) or other substrate, and embedded within a larger microfluidic system.

Method and System for Ultra High Dynamic Range Nucleic Acid Quantification

Researchers at UC Irvine developed a device and method that combines the high dynamic range and high accuracy of digital PCR (dPCR) with the real-time analysis of quantitative PCR (qPCR) to achieve a ultra-high dynamic range PCR over 10 to 12 orders of magnitude. The present method is accomplished by a highly integrated design that optimally packs, thermocycles, and images as many as 1 million reaction vessels.

Use of mutant Kv7.2 channels for anti-epileptic and pain therapies

During seizures or pain-induced inflammation, excess chemical mediators suppress potassium channels mediating neuronal activity and thereby inactivate new generation anti-epileptic drugs and painkillers acting on those channels. The invention describes a gene therapy using a genetically-engineered potassium channel that reduces adverse effects by silencing neuronal hyperactivity while maintaining normal neuronal activity in the presence of chemical mediators to treat epilepsy and pain.

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.

Somatic loss of Mgat1 as a potential risk factor for Multiple Sclerosis (MS)

Researchers at UCI report the incidence of somatic mutation/ loss in a human gene to increase the risk of some types of Multiple Sclerosis (MS).

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.

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.

Massively-Parallel Genetic Screening Tool

Most high throughput genetic screening technology relies on phenotypes that can be coupled to an easily-detectable phenotype, such as fluorescent cell sorting, cell imaging, or cell death. However, many genetic variants may result in a phenotype that is much more subtle and cannot be easily detected by existing screening technologies. It is currently difficult for researchers to examine a variety of different outcomes in one setting, with many of those parameters not being possible to quantify. Being able to assess the functional outcomes on a larger number of individual cells may substantially improve the efficiency of screening.

Continuous, enhanced detection of droplet contents in electrical impedance spectroscopy

The inventors at UCI have developed a method and system to make enhanced electrical impedance spectroscopy measurements in a continuously flowing train of microfluidic droplets. The technique increases the sensitivity of the electrical impedance spectroscopy measurements, lowering detection limits and increasing the frequency of continuous measurements.

RNA-directed Cleavage and Modification of DNA using CasY (CRISPR-CasY)

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;} The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets.  Class 2 CRISPR-Cas are streamlined versions in which a single Cas protein bound to RNA is responsible for binding to and cleavage of a targeted sequence. The programmable nature of these minimal systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation.  Current CRISPR Cas technologies are based on systems from cultured bacteria, leaving untapped the vast majority of organisms that have not been isolated.  There is a need in the art for additional Class 2 CRISPR/Cas systems (e.g., Cas protein plus guide RNA combinations).     UC Berkeley researchers discovered a new type of Cas protein, CasY.  CasY is short compared to previously identified CRISPR-Cas endonucleases, and thus use of this protein as an alternative provides the advantage that the nucleotide sequence encoding the protein is relatively short.  CasY utilizes a guide RNA to perform double stranded cleavage of DNA. The researchers introduced CRISPR-CasY into E. coli, finding that they could block genetic material introduced into the cell.  Further research results indicated that CRISPR-CasY operates in a manner analogous to CRISPR-Cas9, but utilizing an entirely distinct protein architecture containing different catalytic domains.   CasY is also expected to function under different conditions (e.g., temperature) given the environment of the organisms that CasY was expressed in.  Similar to CRISPR Cas9, CasY enzymes are expected to have a wide variety of applications in genome editing and nucleic acid manipulation.   

RNA-directed Cleavage and Modification of DNA using CasX (CRISPR-CasX)

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;} The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets.  Class 2 CRISPR-Cas are streamlined versions in which a single Cas protein bound to RNA is responsible for binding to and cleavage of a targeted sequence. The programmable nature of these minimal systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation.  Current CRISPR Cas technologies are based on systems from cultured bacteria, leaving untapped the vast majority of organisms that have not been isolated.  There is a need in the art for additional Class 2 CRISPR/Cas systems (e.g., Cas protein plus guide RNA combinations).   UC Berkeley researchers discovered a new type of Cas protein, CasX, from groundwater samples. CasX is short compared to previously identified CRISPR-Cas endonucleases, and thus use of this protein as an alternative provides the advantage that the nucleotide sequence encoding the protein is relatively short.  CasX utilizes a tracrRNA and a guide RNA to perform double stranded cleavage of DNA. The researchers introduced CRISPR-CasX into E. coli, finding that they could block genetic material introduced into the cell.  Further research results indicated that CRISPR-CasX operates in a manner analogous to CRISPR-Cas9, but utilizing an entirely distinct protein architecture containing different catalytic domains.   CasX is also expected to function under different conditions (e.g., temperature) given the environment of the organisms that CasX was expressed in.  Similar to CRISPR Cas9, CasX enzymes are expected to have a wide variety of applications in genome editing and nucleic acid manipulation. 

Controllable Emulsification And Point-Of-Care Assays Driven By Magnetic Induced Movement Of The Fluid

UCLA researchers in the department of Bioengineering have developed a novel microfluidic droplet generation technique, where instead of pumps, only magnetic force is used for controllable emulsification of ferrofluid containing solutions. 

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.

Sensitive, Specific Ratiometric Fluorescence-based DNA Detection

Fluorescent silver nanoclusters for nucleic acid detection. 

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.  

Methods For Obtaining A Synthetic Long Sequencing Read Using Short Read Sequencing

UCLA researchers in the Department of Chemistry and Biochemistry have developed a method to increase the functional read length of existing short read next-generation sequencing (NGS) technologies through a novel library preparation that maintains contiguous coverage of long sequences. 

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.  

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