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Protein Inhibitor of Type II-A CRISPR-Cas System

The inventors have discovered three protein inhibitors of the type II-A CRISPR-Cas system that specifically inhibit Cas9 from staphylococcus aureus. This finding is of potential importance to many companies in the CRISPR space. 

Fumigant Detoxification via Reusable Cotton Material

Researchers at the University of California, Davis have developed wearable, highly adsorptive, cotton fabrics that can neutralize fumigants in both open-air and sequestered environments.

Protein Inhibitor of Type VI-B CRISPR-Cas System

The inventors have discovered the first protein inhibitor of the type VI-B CRISPR-Cas system. By controlling this CRISPR system, one could possibly ameliorate the toxicity and off-target cleavage activity observed with the use of the type VI CRISPR system. Moreover, these proteins can also serve as an antidote for instances where the use of CRISPR-Cas technology poses a safety risk. Additionally, this technology can also be used for engineering genetic circuits in mammalian cells. This finding is of potential importance to many companies in the CRISPR space. 

Improved guide RNA and Protein Design for CasX-based Gene Editing Platform

The inventors have developed two new CasX gene-editing platforms (DpbCasXv2 and PlmCasXv2) through rationale structural engineering of the CasX protein and gRNA, which yield improved in vitro and in vivo behaviors. These platforms dramatically increase DNA cleavage activity and can be used as the basis for further improving CasX tools.The RNA-guided CRISPR-associated (Cas) protein CasX has been reported as a fundamentally distinct, RNA-guided platform compared to Cas9 and Cpf1. Structural studies revealed structural differences within the nucleotide-binding loops of CasX, with a compact protein size less than 1,000 amino acids, and guide RNA (gRNA) scaffold stem. These structural differences affect the active ternary complex assembly, leading to different in vivo and in vitro behaviors of these two enzymes.

Metabolic Assessment to Diagnose Equine Neuroaxonal Dystrophy (eNAD)/ Equine Degenerative Myeloencephalopathy (EDM)

Researchers at the University of California, Davis have developed a protocol and assay to assess the rate of metabolism of vitamin E in horses that serves as a potential diagnostic test for equine neuroaxonal dystrophy (eNAD) and equine degenerative myeloencephalopathy (EDM).

Immunogenic Composition to Prevent Francisella Infections in Fish

Researchers from the University of California, Davis are part of a multi-institution research team that has developed a vaccine with proven efficacy in preventing Francisella infections in fish.

Compositions And Methods For Allelic Gene Drive Systems And Lethal Mosaicism

Efficient super-Mendelian inheritance of transgenic insertional elements has been demonstrated in flies, mosquitoes, yeast, and mice. While numerous potentially impactful applications of such so-called gene-drive systems have been proposed they are currently limited to copying relatively large DNA cargo sequences (~1-10 Kb). Many desired genetic traits (e.g., drought tolerance in plants, crop yield, pest-resistance, or insecticide sensitivity), however, result from allelic variants altering only one or a few base pairs. An efficient system for super-Mendelian inheritance of such subtle genetic variants would accelerate a wide array of efforts to disseminate favorable traits throughout populations, or to assemble complex genotypes consisting of point-mutant alleles in combination with insertional transgenes for a multitude of research and applied purposes.

Chimeric Cas9 Variants With Novel Engineered Enzymatic Activities

In this invention, the HNH domain of a Cas9 is replaced by a domain that could have diverse enzymatic activities. This invention enables engineering of Cas9 chimeras that possess novel, conformation-sensitive enzymatic activity to perform specific genome editing in vitro, in vivo, and ex vivo.Prior to this invention, all of the strategies to engineer Cas9 fusion proteins and provide Cas9 with non-natural enzymatic activity for genome manipulations were engineered by fusing specific domains to the N- or C-terminus of Cas9 via long and flexible linkers, or through domain insertion approach. The disadvantages of these synthetic Cas9 chimeras are that the attached domain is on the long flexible linker, and it is very dynamic. Thus, these fusions have a broad activity window and they are large, which makes it difficult to deliver them to the cells. 

Applying a Machine Learning Algorithm to Canine Radiographs for Automated Detection of Left Atrial Enlargement

Researchers at the University of California, Davis have developed a method of detecting canine left atrial enlargement as an early sign of mitral valve disease by applying machine learning techniques to thoracic radiograph images.

Predictive Controller that Optimizes Energy and Water Used to Cool Livestock

Researchers at the University of California, Davis have developed a controller that applies environmental data to optimizing operations of livestock cooling equipment.

Methods for Producing Cultured Meat that has Heterogeneous Composition

UCLA researchers in the Departments of Integrative Biology and Physiology and Molecular, Cellular, and Developmental Biology have developed a novel method for the production of marbled, cultured meat with desirable texture and flavor.

Single Conjugative Vector for Genome Editing by RNA-guided Transposition

The inventors have constructed conjugative plasmids for intra- and inter-species delivery and expression of RNA-guided CRISPR-Cas transposases for organism- and site-specific genome editing by targeted transposon insertion. This invention enables integration of large, customizable DNA segments (encoded within a transposon) into prokaryotic genomes at specific locations and with low rates of off-target integration.

A Wearable Platform for In-Situ Analysis of Hormones

UCLA researchers in the Department of Electrical and Computer Engineering have developed a highly sensitive, wearable hormone monitoring platform.

Method To Implement A Crispr-Cas9 Copycat Gene Drive In Rodents

Currently, alleles at multiple loci in the mouse genome must be combined by Mendelian genetics in crosses of animals to one another to produce a desired compound mutant genotype. For example, to combine homozygous mutations at two loci, animals that are heterozygous for each gene must be produced by breeding, and these are subsequently crossed to one another. Since the frequency of homozygosity for each allele is 1:4 the frequency of homozygosity for both genes is 1:16. Since the average litter of mice is approximately 10 pups, and the generation time from conception to reproductive age is about 3 months, this requires a substantial number of animals and time. With the addition of each new locus (three, four, etc), the cost measured in animals, time, and money increases exponentially. These factors increase substantially more if two or more loci are genetically linked, which requires rare recombination events to combine engineered alleles on the same chromosome. The CRISPR-Cas9 gene drive system stands to revolutionize rodent breeding. If each desired allele is encoded as a gene drive element that contains an sgRNA designed to target the same genomic location in the wild type homologous chromosome, each locus will be “driven” to homozygosity in the presence of Cas9. Therefore, in order to combine three alleles, for example, a mouse with one gene drive element (A) would be crossed to a mouse that encodes Cas9. Offspring of this cross would then be crossed to mice carrying gene drive element B, and these offspring would be crossed to mice carrying gene drive element C. In the presence of Cas9 at each generation, these gene drive elements at three distinct loci will be converted to homozygosity such that 50% of offspring, those that inherit Cas9, will be triple homozygous after three generations, even if they are genetically linked loci. A CRISPR-Cas9 mediated gene drive leverages the native cellular mechanism of homology directed repair to copy a desired allele from one chromosome to another. This process can convert a heterozygous genotype to homozygosity in a single generation. While CRISPR-Cas9 gene drives have been implemented in two species of insects, flies and mosquitos, it has not been reported in any non-insect animal species. 

DNA Methylation: A New Method for the Quantitative Predictor Of Age In Dogs

The ability to properly estimate the age of dogs would be quite useful in a variety of ways. For example, proper age estimation is important because age often plays a significant role when making medical decisions for pets. Currently, the accepted method to estimate age in dogs is based on the quality of teeth as well as ocular features. Estimating age based on tooth-wear (the commonly used metric in shelters) is very inaccurate after the teeth have fully erupted, generally by 6-7 months of age in dogs. Unfortunately, these methods have an accuracy of ~50% at best for domesticated pets and is error-prone for dogs between 2-8 years, encompassing a large portion of a dog’s adult life. Thus, shelters commonly underestimate the ages of these dogs to increase the likelihood of dogs being adopted, as people generally have a preference for younger pets. 

Targeted Ionophore-Based Metal Supplementation

Metal deficiency is implicated in a variety of genetic, neurological, cardiovascular, and metabolic diseases. Current approaches for addressing metal deficiency rely on generic metal ion supplementation, which can potentially lead to detrimental off-target metal accumulation in unwanted tissues and subsequently trigger oxidative stress and damage cascades. The inventors have developed a new modular platform for delivering metal ions in a tissue-specific manner and demonstrate liver-targeted copper supplementation as a proof of concept of this strategy. Specifically, the inventors designed and synthesized a N-acetylgalactosamine-functionalized ionophore, Gal-Cu(gtsm), to serve as a copper-carrying “Trojan Horse” that targets liver-localized asialoglycoprotein receptors (ASGPRs) and releases copper only after being taken up by cells, where the reducing intracellular environment triggers copper release from the ionophore. The inventors utilized a combination of bioluminescence imaging and inductively-coupled plasma mass spectrometry assays to establish ASGPR-dependent copper accumulation with this reagent in both liver cell culture and mouse models with minimal toxicity. The modular nature of this synthetic approach presages that this platform can be expanded to deliver a broader range of metals to specific cells, tissues, and organs in a more directed manner to treat metal deficiency in disease. This patent broadly covers directed metal delivery to select organs, tissues, and organelles.

Phenotypic Age And DNA Methylation Based Biomarkers For Life Expectancy And Morbidity

UCLA researchers in the Departments of Human Genetics and Biostatistics have combined phenotypic age and DNA methylation patterns to developed a novel biomarker for biological age.

Composition Of Matter And Method For Leptospirosis Vaccine

Leptospirosis is one of the most widespread diseases estimated to infect up to 7-10 million people per year worldwide (2014) that can be transmitted from animals to humans. The most common transmission is via the urine of rodents or domestic animals that contaminates water or soil. Unfortunately, it can cause severe infection and currently there is not an efficient vaccine present to combat this disease. The disease is caused by Leptospira, a genus of the spirochaete bacteria of which there are ~13 pathogenic species that effect humans. The signs and symptoms of the disease are quite variable and can range from mild headaches, muscle pains, and fevers to the more severe form which causes bleeding from the lungs.

Human Respiratory Disease Model Developed from Titi Monkey Adenovirus

Researchers at the University of California, Davis have cultured a titi monkey adenovirus (TMAdV,) and used the virus to develop a model of human respiratory disease.

Label Free Assessment Of Embryo Vitality

Researchers at UC Irvine developed an independent non-invasive method to distinguish between healthy and unhealthy embryos.

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 within the device.Counteracting these vortices allows for single particle encapsulation in the droplets formed by the device and thereby makes this technology a good candidate for use in single cell diagnostics and drug delivery systems.

Production of Glycolipid PEFAs from Yeasts

Method of using basidiomycetous yeasts to convert carbohydrates to glycolipid biosurfactants

A Micro/Nanobubble Oxygenated Solutions for Wound Healing and Tissue Preservation

Soft-tissue injuries and organ transplantation are common in modern combat scenarios. Organs and tissues harvested for transplantation need to be preserved during transport, which can be very difficult. Micro and nanobubbles (MNBs) offer a new technology that could supply oxygenation to such tissues prior to transplantation, thus affording better recovery and survival of patients. Described here is a novel device capable of producing MNB solutions that can be used to preserve viability and function of such organs/tissue. Additionally, these solutions may be used with negative pressure wound therapy to heal soft-tissue wounds.

Novel Molluscicide

  Background: Slugs and snails are among the most problematic invasive agricultural and horticultural pests. They cause crop loss, reduce crop yield and quality, cause product shipment rejection, and transmit plant and human pathogens. The most commonly used chemical molluscicides are toxic to pets and other organisms. These chemical pesticides are also harmful to the environment, are not cost effective, and with variable effficacy that is highly influenced by environmental conditions such as moisture.   Brief Description: UCR researchers have developed a novel potential biopesticide that targets slugs and snails using the recently discovered US strain of the nematode species Phasmarhabditis hermaphrodita. The European strain of this nematode (Nemaslug ®) is being used to successfully manage slugs and snails in Europe. Recent surveys show that consumers in the US are willing to pay more for a more effective and environmentally safe pest management alternative for these invasive gastropods. Phasmarhabditis hermaphrodita (singly or in combination with P. californica or P. papillosa) can be used effectively to manage slug and snail infestations, notably European brown garden snail (Cornu aspersum), Giant African land snail (Lissachatina fulica), gray field slug (Deroceras reticulatum) and greenhouse slug (Lehmannia valentiana).  

New Effective Low-Cost Vaccines

Enteric disease and respiratory diseases are major problems worldwide which greatly impact human health, as well as animal health. Current vaccine approaches are limited by numerous factors, including production costs, efficacy, safety, requirement of adjuvants, and storage conditions. 

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