42 results about "Screening assay" patented technology

The field of the invention belongs to in vitro assays for producing an in vitro organ culture system, and the use of such an in vitro organ culture system for screening assays in the context of drug screening, patient selection, and personalized medicine. More specifically, the invention relates to an in vitro method of establishing tumor organoids from a cancer tissue sample obtained from a subject, to an in vitro method of providing autologous tumor organoid-activated immune cells, to a method of preparing an in vitro organ culture system for mimicking tumor interaction with an immune system of a subject, as well as to the in vitro organ culture system produced thereby, to a method for determining the responsiveness of a tumor to a treatment with at least one immune- oncologic drug applying said in vitro organ culture system, and a kit-in-parts for preparing an in vitro organ culture system mimicking tumor interaction with an immune system of a subject, as disclosed herein.

Compositions and methods for enzymes with altered properties are provided, which include a systematic approach to mutagenesis and a screening assay that allows selection of desired proteins. Embodiments of the method are particularly suitable for altering specific properties of restriction endonucleases, such as star activity. The composition includes a restriction endonuclease with reduced star activity, as defined by an overall fidelity index improvement factor.

The field of the invention is in vitro assays for the production of in vitro organ culture systems and the use of such in vitro organ culture systems for screening assays in drug screening, patient selection and personalized medical context. More specifically, the present invention relates to an in vitro method of establishing a tumor organoid from a cancer tissue sample obtained from a subject, an in vitro method of providing immune cells activated by an autologous tumor organoid, a method of preparing an in vitro organ culture system for mimicking interaction of a tumor with an immune system of a subject, and a method of preparing an in vitro organ culture system for mimicking interaction of a tumor with an immune system of a subject. The invention relates to an in vitro organ culture system, and to an in vitro organ culture system produced thereby, to a method for determining the reactivity of a tumor to at least one immunooncology drug therapy using said in vitro organ culture system, and to a kit for preparing an in vitro organ culture system that mimics the interaction of a tumor with the immune system of a subject, as disclosed herein.

Screening assays are used to identify mutant homogentisate solanesyl transferase (HST) enzymes which are at least partially resistant to HST-inhibiting herbicides. Nucleic acids encoding the mutant HST enzyme proteins are made available and useful in modifying plants and plant parts so that they can be made herbicide resistant. Crop plants which express the mutant HST enzymes can be grown in the field and herbicides used to controlling unwanted other vegetation. The homogentisate solanesyltransferase (HST) enzyme or an active fragment thereof comprises the amino acid sequence motif: F[V / M]TX[F / Y] (SEQ ID NO: 1), wherein X is any amino acid; and wherein one or more of the amino acid residues of the motif are mutated.

Antibodies that bind to SNAP-25 are provided. Botulinum toxin potency screening assays that utilize anti-SNAP-25 antibodies are also provided.

The present invention is in the field of triacylglyccrol synthesis. In particular the invention relates to the identification of DIESL as a new triacylglycerol synthase. The invention also relates to the identification of TMX1 as a negative regulator of DIESL mediated triacylglycerol synthesis. Screening assays for identifying agents that modulate the activity of DIESL and / or of TMX1, or that modulate the interaction between DIESL and TMX1 are also provided.

A method of screening candidate agents for their ability to modulate RAGE activity where such RAGE activity is induced by an active co-located GPCR, the method comprising the steps of: contacting a RAGE polypeptide with a GPCR polypeptide in the presence of a candidate agent where the GPCR polypeptide is constitutively active and / or is activated by addition of an agonist, partial agonist or allosteric modulator of that GPCR; and detecting whether the candidate agent is a modulator of RAGE ligand-independent activation of RAGE by activated co-located GPCR by detecting an effect indicative of modulation of RAGE activation by the presence of the candidate agent and / or by detecting RAGE-dependent signalling that is modulated by the presence of the candidate agent.

Compositions and methods for modulation by upregulation (up modulation) and / or downregulation (down modulation) of mitophagy are described for the treatment of mitochondrial disorders including OPA-1 related disease and Single Large Scale Mitochondrial DNA Deletion (SLSMD). Also disclosed are a number of screening assays and gene targets having utility for the identification of agents which modulate the phenotype associated with such disorders.

The invention provides for a screening assay-using a selective proteolysis of recombinant full-length PIKfyve at an endogenous caspase 3 cleavage site to liberate the 34 kDa C -terminal kinase domain. Despite instability of the kinase domain to isolation, the liberated kinase domain is stable in the presence of the N-terminal PIKfyve protein fragment and can thus be treated with compounds of interest and analyzed by mass spectrometry, such as RapidFire-MS, with each injection taking under one minute. The assay was established to triage small molecules for covalent modification of PIKfyve. The assay was also established using cysteine-mutant proteins, where the reactive cysteine was replaced with an inert amino acid which when run through the same experimental protocol, was used to confirm adduct formation at the target cysteine.

Disclosed herein are 3D printed vascular tissues and compositions and methods for making the 3D printed vascular tissues. The 3D printed vascular tissues can be used to model vascular tissue damage (e.g., vascular leakage) and in screening assays for agents that cause or inhibit or treat vascular tissue damage.

Aspergillus flavus is an opportunistic, saprophytic fungus that infects maize and other fatty acid-rich food and feed crops and produces toxic and carcinogenic secondary metabolites known as aflatoxins. In vitro studies showed a five-fold increase in antifungal activity of AGM182 (vs. tachyplesin1) against A. flavus. Transgenic maize plants expressing AGM182 under maize Ubiquitin-1 promoter were produced through Agrobacterium-mediated transformation. PCR products confirmed integration of the AGM182 gene, while RT-PCR of maize RNA confirmed the presence of AGM182 transcripts. Maize kernel screening assay using a highly aflatoxigenic A. flavus strain (AF70) showed up to 72% reduction in fungal growth in the transgenic AGM182 seeds compared to isogenic negative control seeds.

Trypsin / trypsin-like proteases have been reported to be facilitating SARS-COV-2 entry into host cells. Spike has protease cleavage sites between the S1 and S2 domains. Cleavage property of proteases can be used to design drug screening assays meant for screening antiviral candidates against spike cleavage. In the claimed invention we have developed a proof-of-concept assay system for screening drugs against proteases which cleave spike between S1 and S2. We designed a fusion substrate protein containing a reporter protein, the protease cleavage site between S1 and S2 and a cellulose binding domain. The substrate protein can be immobilized on cellulose due to the presence of cellulose binding domain (CBD). When proteases cleave the substrate. CBD remains bound to cellulose and the reporter protein is dislodged. The released reporter can be used as read out of protease activity.

A method for designing a cell-based screening assay experiment includes, at a graphical user interface, receiving a first input identifying a template plate definition and receiving a second input defining a first group of disease reagents and at least one destination concentration of the disease reagents. The method also includes receiving a third input defining a first group of treatment reagents, at least one destination concentration for the treatment reagents, a number of replicates of the treatment reagents, and a selection to associate the first group of treatment reagents with the first group of disease reagents. The method further includes generating, based at least partially on the inputs, a design for the cell-based screening assay experiment, including determining a number of test wells required for performing the experiment, and distributing the test wells over a one or more test plates that are instances of the template plate definition.

The disclosure provides methods for diagnosis or prediction of the likelihood of a subject experiencing obstructive sleep apnea, determined at least in part by measuring the degree of tongue fat in a subject using, e.g., thermal imaging, THz imaging or other multispectral imaging.

A method for screening and detecting biological particles includes the following steps: providing a biological particle screening and detection system, comprising a flow channel, an optical detection component, and a carrier disk, wherein the optical detection component provides a detection optical path that penetrates the flow channel, and the optical detection component is used to sense a target biological particle; providing a sample; diluting the sample to form a test solution; controlling the test solution to flow into the flow channel from an inlet end; and when the optical detection component senses the target biological particle in the test solution, the carrier disk is controlled to move to an outlet end of the flow channel, wherein the carrier disk contains a diluent, and a portion of the solution containing the target biological particle in the test solution is controlled to be discharged from the outlet end and then loaded onto the carrier disk to dilute the portion of the solution.

The invention provides agonistic anti-human VISTA antibodies and antibody fragments. These agonist antibodies and antibody fragments may be used to potentiate or enhance or mimic VISTA's suppressive effects on T cell immunity and thereby suppress T cell immunity. These agonist antibodies and antibody fragments are especially useful in the treatment of autoimmunity, allergy, inflammatory conditions, GVHD, sepsis and transplant recipients. Screening assays for identifying these agonists are also provided.

The present disclosure relates to a clinical genetic screening assay that designates a subset of high-risk segments within a next generation sequencing (NGS) sample for confirmatory testing. Particularly, aspects are directed towards obtaining (i) regions of interest (ROIs) and associated variant data, (ii) population allele frequency information, and (iii) a sensitivity profile, performing NGS on a sample obtained from a subject to obtain NGS read data for the ROIs, performing a rescue minimization protocol to designate a subset of ROIs for Sanger resequencing, and performing Sanger resequencing on the subset of ROIs. The NGS read data and the Sanger resequencing data are used to generate accurate variant callings and / or diagnosis for the subject.

Disclosed herein is a method for maturing immature cardiomyocytes (immature hiPSC-CMs) derived from human induced pluripotent stem cells in culture using a cell-derived extracellular matrix (AFC-ECM) derived in vitro from cells isolated from amniotic fluid to form mature cardiomyocytes. Also disclosed herein is a cell construct comprising a monolayer of these mature cardiomyocytes on AFC-ECM for use in cardiotoxicity and / or arrhythmogenic screening assays of drug compounds. Also disclosed herein is a method for determining the cardiotoxicity and / or arrhythmogenic effects of drug compounds in vitro using such a cell construct.

Disclosed are methods of using a cell-derived extracellular matrix derived in-vitro from cells isolated from amniotic fluid (AFC-ECM) for the maturation of immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs) in culture forming mature cardiomyocytes. Also disclosed is a cell construct comprising a monolayer of these mature cardiomyocytes on an AFC-ECM useful for cardiotoxicity and / or proarrhythmic screening assays of drug compounds. Also disclosed are methods for determining the cardiotoxicity and / or proarrhythmic effect of a drug compound in vitro using such cell constructs.

The present disclosure provides methods of generating neural precursor cells having glial preference from induced pluripotent cells and further differentiating the neural precursor cells into astrocytes. Further provided herein are methods of screening assays using astrocytes, models that mimic the human brain, and cell therapies.

The present disclosure provides a compound screening method comprising screening a test compound that binds a target protein of interest and another ligand protein that is not previously known to form a complex, comprising, (i) in the presence and absence of a test compound, incubating an immobilized ligand protein with a target protein of interest, comprising a nucleic acid tag, wherein the protein of interest and the nucleic acid tag differ from each other; (ii) removing unbound target protein of interest; and (iii) detecting the presence or absence of complex between the immobilized ligand protein, test compound, and the target protein of interest, wherein an increase in the amount of target protein of interest bound to the immobilized ligand protein in the presence of test compound as compared to the absence of test compound indicates the test compound binds to and enables protein-protein complex formation between the immobilized ligand protein and the target protein of interest.

Provided herein are methods and kits for detecting the presence of DNA mutations in the KRAS, BRAF, CTNNB1, and APC genes. The methods and kits employ microcarriers, each of which has a probe specific for a DNA mutation in the KRAS, BRAF, CTNNB1, or APC gene and an identifier unique to the probe sequence. After isolating and amplifying DNA from a sample, hybridization of the amplified DNA with a probe specific for a DNA mutation coupled to the microcarrier indicates the presence of a DNA mutation in the sample. Because each microcarrier can be identified by detecting the identifier, a multiplex screening assay for multiple mutations in each of the KRAS, BRAF, CTNNB1, and APC genes is provided.

Identification of OR5A2 as an Olfactory Receptor that binds natural musk and synthetic musks and using the interaction of OR5A2 polypeptides and nitromusk, polycyclic musk, macrocyclic musk and alicyclic musks as a basis of screening assays for agents that specifically modulate the activity of the Olfactory Receptor.

The present invention provides methods for diagnosing disease by detecting extracellular vesicle-derived markers, as well as other diagnostic and screening assays. The methods include, but are not limited to, the analysis of extracellular vesicle-derived biomarkers obtained from a bodily fluid sample. The methods include, but are not limited to, diagnostic and screening assays, including medical imaging. In one aspect, the present disclosure provides techniques for the detection and / or screening of various cancers. In another aspect, the techniques provided herein are suitable for selecting and / or monitoring and / or assessing the efficacy of a treatment administered to an individual determined to have or be susceptible to cancer.

It provides a modulator of receptor activation associated with specific diseases and / or conditions. [Solution] A modulator of RAGE activity is provided, wherein the RAGE activity is induced by an active coexisting GPCR.

The present disclosure provides methods for generating glial-biased neural progenitor cells from induced pluripotent cells and further differentiating the neural progenitor cells into astrocytes. Further provided herein are methods for using astrocytes in screening assays, models that mimic the human brain, and cell therapy.

Kits, compositions, and methods for detection of Candida auris make use of nucleic acid molecules that specifically bind a target region of 18S rRNA or 28S rRNA of Candida auris. The ultrasensitive detection of Candida auris 18S rRNA at concentrations at least 100-fold higher than the coding genomic DNA means this RT-PCR approach is capable of detecting a single colony forming unit of C. auris. The assay is also specific for C. auris and does not detect other Candida species. This approach leverages the biologically amplified nature of C. auris 18S and 28S rRNA as compared to the coding DNA and provides a highly sensitive screening assay for C. auris in healthcare or other settings. The assay is amongst the most sensitive and specific approaches for C. auris screening, and can be adapted in high-throughput laboratory approaches.

The present disclosure relates to a clinical genetic screening assay that designates a subset of high-risk segments within a next generation sequencing (NGS) sample for confirmatory testing. Particularly, aspects are directed towards obtaining (i) regions of interest (ROIs) and associated variant data, (ii) population allele frequency information, and (iii) a sensitivity profile, performing NGS on a sample obtained from a subject to obtain NGS read data for the ROIs, performing a rescue minimization protocol to designate a subset of ROIs for Sanger resequencing, and performing Sanger resequencing on the subset of ROIs. The NGS read data and the Sanger resequencing data are used to generate accurate variant callings and / or diagnosis for the subject.

Described herein is a method of quality assurance for high throughput screening systems that uses control nucleic acids to detect and diagnose sample loss, contamination, and suboptimal process steps.

A method of screening for a candidate substance according to the ability of the candidate substance to modulate RAGE activity wherein such RAGE activity is induced by a co-localized active-type GPCR, the method comprising the steps of contacting a RAGE polypeptide with a GPCR polypeptide in the presence of a candidate substance, wherein the GPCR polypeptide is constitutively active and / or activated by the addition of an agonist, a partial agonist or an allosteric modulator of the GPCR; and detecting whether the candidate substance is a modulator of RAGE ligand-independent RAGE activation by co-localized activation-type GPCR by detecting an effect indicative of RAGE activation modulated by the presence of the candidate substance and / or by detecting RAGE-dependent signaling modulated by the presence of the candidate substance.