344 results about "Aggresome" patented technology

The invention relates to a T7 RNA polymerase mutant and application thereof. Specifically, the invention discloses a T7 RNA polymerase mutant, and the polymerase mutant has at least one amino acid mutation at sites corresponding to a wild type T7 RNA polymerase and selected from the following groups: the 44th site, the 45th site, the 46th site, the 172nd site, the 389th site, the 425th site, the 441st site, the 632th site, the 643th site, the 754th site and the 789th site; the serial number of the mutation site is based on the sequence shown in SEQ ID NO: 1, the mutation leads to obvious reduction of a byproduct dsRNA generated in the process of enzyme synthesis of mRNA, and meanwhile, the generation of RNA aggregates is reduced.

The invention discloses a chimera for degrading a CARD structural domain protein aggregate and application of the chimera. The chimera is prepared from light-operated targeting protein and light-operated degradation protein, the light-operated targeting protein is sequentially connected by an MAVS CARD structural domain, a flexible connecting peptide and a photosensitive protein pMag; the light-controlled degradation protein is sequentially connected by a photosensitive protein nMag, a flexible connecting peptide and an RING structural domain of TRIM21. According to the application, a light-operated activated CARD-RING chimera is constructed, and when the CARTAC generates toxic and side effects or in cells with RIG-I / MDA5 signal channels abnormally activated, the activity of the CARTAC can be effectively controlled or autoimmune diseases caused by RIG-I / MDA5 abnormity can be inhibited.

The invention provides a self-assembled cross-linked enzyme aggregate based on a protein scaffold and a preparation method of the self-assembled cross-linked enzyme aggregate, and belongs to the technical field of biology. The preparation method comprises the following steps: connecting an enzyme connected with SpyTag to a SpyCatcher protein scaffold to form a self-assembled cross-linked enzyme aggregate; the amino acid sequence of the SpyCatcher protein is as shown in SEQ ID NO: 1. According to the self-assembled cross-linked enzyme aggregate prepared by the invention, the conformation and the enzyme activity of the enzyme are reserved to the maximum extent, meanwhile, the thermal stability and the reusability are improved, and a foundation is laid for subsequent industrial utilization.

The invention provides a bispecific antibody and a purification method thereof. The purification method comprises the following steps: a) loading a sample containing a bispecific antibody to a affinity chromatographic column, and leaching and eluting; the biomacromolecules in the sample are adsorbed on the affinity chromatography column in the leaching stage, the biomacromolecules comprise antibodies, host cell proteins and protein aggregates, and the antibodies comprise bispecific antibodies and homodimers; separating the antibody from the affinity chromatography column in the elution stage, and collecting the eluate in the elution stage; b) loading the eluent to a hydrophobic membrane material, carrying out flow-through, and collecting a flow-through liquid containing the purified antibody; and the flow-through liquid used for flow-through contains 0.73 to 0.77 M of (NH4) 2SO4. The method can solve the problem that homodimers in bispecific antibodies are difficult to efficiently remove in the prior art, and is suitable for the field of antibody purification.

The present invention provides a polypeptide having disaggregase activity for use in medicine, wherein the polypeptide comprises the sequence SEQ ID NO: 1 or SEQ ID NO: 2, or a variant thereof that retains the disaggregase activity, more particularly for use in the prevention or treatment of a disease or disorder associated with protein aggregates in a subject. The invention also provides an expression vector encoding the polypeptide for the same use, and uses and methods for eliminating or preventing the formation of a protein aggregate in a protein-containing composition. The invention also provides the use of the polypeptide for imaging a protein aggregate and for the diagnosis and prognosis of a disease associated with protein aggregates.

The invention discloses a boron difluoride curcumin skeleton compound as shown in a formula (I), and belongs to the field of medical imaging molecular probes. The boron difluoride curcumin skeleton compound disclosed by the invention has the characteristics of near-infrared emission and large Stokes shift, can be used as a fluorescent probe for marking key pathological proteins such as beta-amyloid protein (Abeta) aggregate of Alzheimer's disease (AD) and the like, and has the characteristics of high sensitivity, high signal-to-noise ratio and high imaging; in addition, in-vivo level A beta imaging can be realized through a blood brain barrier. The boron difluoride curcumin skeleton compound disclosed by the invention also has a treatment effect and can be used for remarkably inhibiting A beta monomers from forming aggregates and depolymerizing A beta aggregates, and meanwhile, the compound shown as the formula (I) is used for remarkably inhibiting A beta-induced microglial cell inflammatory response. The invention also provides a preparation method of the boron difluoride curcumin skeleton compound, an intermediate compound and application of the boron difluoride curcumin skeleton compound. # imgabs0 #

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of ATXN3 mRNA in a cell or animal, and in certain instances reducing the amount of Ataxin-3 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to prevent or ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include ataxia, neuropathy, and aggregate formation. Such neurodegenerative diseases include SCA3.

The invention discloses a method for constructing an organoid. The method comprises the following steps: (1) carrying out hanging drop culture on testicular supporting cells and primordial germ cell-like cells in an organoid culture solution according to a quantity ratio of 1: (2-6) to obtain cell aggregates; (2) culturing the cell aggregate in a gas-liquid phase culture system to obtain an organoid; wherein the content of double positive cells in the primordial germ cell-like cells is greater than 40%, the gas-liquid phase culture system comprises a solid culture medium and an organoid culture solution, and the solid culture medium is formed by the organoid culture solution and agarose gel; wherein the organoid culture solution is prepared from human bone morphogenetic protein-4, a basic fibroblast growth factor, a glial cell-derived neurotrophic factor and retinoic acid. The organoid obtained by the method has a high germ cell population proportion.

The present disclosure provides materials and methods related to the purification of viral vectors. In particular, the present disclosure provides peptides, compositions, adsorbents, and related methods, capable of removing process-related impurities (e.g., host cell proteins, nucleic acids, and media components) and product-related impurities (e.g., product fragments, product aggregates, and inactive forms derived from product degradation by or association with other species in the cell culture harvest) from samples during the production and purification of adenovirus.

The invention relates to the technical field of immunodetection, in particular to a hybridoma cell strain secreting an anti-threonine phosphorylated tau protein monoclonal antibody. The hybridoma cell strain for secreting the p-tau181 monoclonal antibody is preserved in the China Center for Type Culture Collection, and the preservation numbers of the hybridoma cell strain and the hybridoma cell strain are respectively CCTCC NO: C2024272 and CCTCC NO: C2024273. The hybridoma cell strain can be used for preparing a monoclonal antibody capable of specifically recognizing p-tau181 and aggregate thereof, and the problem that a targeted p-tau181 antibody is lacked at present is solved. The invention has the advantages that the two monoclonal antibodies can be further applied subsequently to prepare a high-specificity and high-sensitivity p-tau181 detection kit, the passive immunological treatment of specific targeting p-tau181 is developed, the disease progress is slowed down, and the blank of the current immunological treatment of targeting p-tau181 is filled up.

The invention discloses a diagnostic marker for Parkinson's disease, application of the diagnostic marker and a heteropolymer detection method, and relates to the technical field of biology. The diagnostic marker is a protein heterozygous aggregate in a brain-derived exosome, and the protein heterozygous aggregate comprises alpha-synuclein and amylin. The invention also provides application of a reagent for detecting the diagnostic marker in preparation of a diagnostic product for Parkinson's disease. According to the present invention, the research results show that the important biomarker protein aggregate in the Parkinson's disease diagnosis is not the aggregate simply formed by polymerizing the alpha-Synuclein (aS) protein, but is doped with the other easily aggregated protein-amylin (Amylin); a heteropolymer composed of aS and Amylin is adopted as a biomarker, and the diagnosis efficiency on the Parkinson's disease can be effectively improved.

The invention belongs to the technical field of enzyme engineering and gene engineering, and particularly relates to a recombinant immobilized enzyme, an expression gene thereof and application of the recombinant immobilized enzyme in production of macrocyclodextrin. According to the preparation method, SpyTag and SpyCatcher peptides are fused to the N end of isoamylase and the N end of 4-alpha-glucanotransferase respectively, the 4-alpha-glucanotransferase modified by the SpyTag and the isoamylase modified by the SpyCatcher are obtained, and after spontaneous isopeptide bonds are formed between the SpyTag and the SpyCatcher, the self-assembled macrocyclodextrin production enzyme cluster is obtained. The obtained macrocyclodextrin production enzyme cluster forms an enzyme aggregate with a three-dimensional structure under the traditional glutaraldehyde-mediated catalytic action, namely the recombinant immobilized enzyme. The recombinant immobilized enzyme disclosed by the invention can be repeatedly utilized, is simple and convenient to operate, is easy to separate a converted product, and can be applied to industrial production of the macrocyclodextrin.

The invention relates to anti-TDP-43 binding molecules and uses thereof. The present invention is in the field of trans-activation responsive DNA binding proteins (TARDB or also referred to as TDP-43) having a molecular weight of 43 kDa. The present invention relates to TDP-43 specific binding molecules, in particular to anti-TDP-43 antibodies or antigen binding fragments or derivatives thereof, and uses thereof. The present invention provides means and methods for diagnosing, preventing, ameliorating and / or treating diseases, disorders and / or abnormalities associated with TDP-43 aggregates, including, but not limited to, frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), chronic traumatic encephalopathy (CTE), and edge-dominant age-related TDP-43 encephalopathy (LATE).

The invention discloses a full-value protein biological feed production method, and relates to the technical field of protein feed production, the production method comprises the following steps: double-strain co-fermentation: cooling fermentable syrup to 38-42 DEG C, adjusting the pH value to 6.5-7.0, inoculating a mixed strain of Thermoactinomyces vulgaris and Candida utilis, fermenting for 18-24 hours under the condition that the dissolved oxygen is maintained to be 30-60%, and carrying out double-strain co-fermentation; in the process, the pH, dissolved oxygen and temperature are monitored in real time by an on-line sensor controlled by a PLC (Programmable Logic Controller), and materials are automatically supplemented; and membrane separation and concentration: enabling the fermentation liquor to pass through a PVDF (Polyvinylidene Fluoride) ultrafiltration membrane with the molecular weight cutoff of 10kDa-30kDa, and intercepting thalli and protein aggregates by a membrane concentration multiple of 5-10 to obtain a membrane concentrated solution with the protein concentration of more than or equal to 50g / L. According to the method, agricultural waste is efficiently converted into complete protein through double-bacterium synergistic fermentation, the problems that traditional single-bacterium fermentation is low in yield and unbalanced in nutrition are solved, and the protein yield is increased.

The present invention relates to novel peptides and uses thereof, and more particularly to peptides having a length of 12 to 20 a.a. comprising an amino acid sequence designated as SEQ ID NO: 1 or 2, having the ability to inhibit the formation of abnormal protein aggregates, wherein 1 to 4 of the amino acids excluding glycine are L-type amino acids and the other amino acids are D-type amino acids.

The present disclosure provides materials and methods related to the purification of a biologic from a biological fluid. In particular, the present disclosure provides compositions, and related methods, comprising peptide ligands capable of removing process-related impurities (e.g., host cell proteins, nucleic acids, and media components) and product-related impurities (e.g., product fragments, product aggregates, and inactive forms derived from product degradation by or association with other species in the cell culture harvest) from biological fluids during the production of a biologic.

The present disclosure relates generally to compositions, systems, and methods for lysing blood samples comprising an infectious agent, for example a bacteria, or a fungus, while maintaining viability of the infectious agent for subsequent characterization, for example phenotyping or genotyping. A lysing composition may include one or more surfactants, such as one or more detergents. A lysing composition may include lysing agent including one or more salts. A lysing composition may include one or more enzymes to break down one or more lyses byproducts, such as nucleic acids and / or protein aggregates.

The present invention relates to an inhibitor of the METTL3-METTL14 complex, or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of neuromuscular degenerative pathologies. These pathologies are preferably caused by or linked to mutations in the FUS gene and / or by the accumulation of pathological protein aggregates or aberrant stress granules. The inhibitor can be used alone or in combination with other pharmaceutically active ingredients. Additionally, the invention includes pharmaceutical compositions comprising the inhibitor and a pharmaceutically acceptable carrier or excipient, potentially combined with other agents known to treat or mitigate neuromuscular disorders.

Provided is a polypeptide capable of dissolving protein aggregates. Also provided is a method of treating a phase separation associated diseases, such as phase separation associated visual disorders (e.g., cataracts) using the polypeptide provided herein.

The invention discloses a protein / polysaccharide composite dialysis membrane based on in-situ loaded lanthanum carbonate and application of the protein / polysaccharide composite dialysis membrane, a lanthanum carbonate loaded protein / polysaccharide composite aggregate is used for modifying a porous filter membrane, and the dialysis membrane with a lanthanum carbonate loaded protein / polysaccharide self-assembled membrane as a compact skin layer and the porous filter membrane as a supporting layer is formed. By integrating a membrane separation mechanism of hemodialysis and an adsorption principle of blood perfusion, the skin layer of the dialysis membrane has molecular sieve separation and chemical adsorption functions, efficient removal of molecular uremic toxins (phosphorus, creatine liver, bilirubin, p-cresol sulfate and indol sulfate) with different sizes is synergistically realized, macromolecular proteins in blood are effectively intercepted by pore size screening, and the dialysis membrane has the advantages of simple structure, low cost and high efficiency. According to the present invention, by using the adsorption effect of the functional group on the surface of the membrane, the high removal rate on the protein-bound urotoxin is achieved, the high removal effect on phosphorus is particularly achieved, the blood compatibility is considered, the large-scale preparation is easily achieved, and the new idea is provided for the development of the high-performance blood purification material.

Novel and useful compounds, such as 2,4-dihydropyrazolo[3',4':4,5]pyrano[2,3-b]pyridines, are disclosed herein. Such compounds may be employed in various treatments, alleviation, or prevention of a group of disorders, such as disorders associated with Tau (tubulin associated unit) protein aggregates, such as neurofibrillary tangles (NFTs), such as Alzheimer's disease (AD).

The invention relates to methods and materials for use in treating neurodegenerative diseases associated with pathological protein aggregates and provides fusion proteins comprising: (i) a first portion comprising a sequence of a protein which aggregates pathologically in neurodegenerative disease, such as tau protein, and (ii) a second portion comprising a RING-type E3 ubiquitin ligase, a component of a RING-type E3 ubiquitin ligase complex, or a domain of either. These fusion proteins have utility in selectively or preferentially targeting pathogenic protein aggregates for degradation.

The present disclosure provides materials and methods related to the purification of viral vectors. In particular, the present disclosure provides compositions, and related methods, comprising peptide ligands capable of removing process-related impurities (e.g., host cell proteins, nucleic acids, and media components) and product-related impurities (e.g., product fragments, product aggregates, and inactive forms derived from product degradation by or association with other species in the cell culture harvest) from biological fluids during the production and purification of adeno-associated viruses (AAVs).

Compounds, methods and pharmaceutical compositions are provided for reducing the amount or activity of PRNP RNA in cells or animals and in some cases reducing the amount of PrP protein in cells or animals. Such compounds, methods and pharmaceutical compositions can be used to improve at least one symptom or sign of neurodegenerative diseases. Such symptoms and signs are spongiform changes in the brain, formation of abnormal protein aggregates, neuronal loss, markers of neuronal loss, rapid progression dementia and death. Such neurodegenerative diseases include prion diseases, Creutzfeldt-Jakob disease (CJD), variant Creutzfeldt-Jakob disease (vCJD), familial Creutzfeldt-Jakob disease (fCJD), Gertzman-Straussler-Schinker syndrome, fatal familial insomnia, kuru, Alzheimer's disease or Parkinson's disease.

The technical problem of the present disclosure is to provide: a composition for promoting the decomposition of protein aggregates; and a pharmaceutical composition for preventing or treating neurodegenerative diseases associated with the formation of protein aggregates. The technical problem is solved by a compound represented by general formula (I).

The present invention relates to a novel indanone derivative, an isomer thereof or a pharmaceutically acceptable salt thereof, and a use thereof, the indanone derivative according to the present invention (i) inhibits aggregation and / or decomposition of aggregates of beta-amyloid protein, ii) inhibits aggregation and / or decomposition of aggregates of Tau protein, and / or iii) inhibits excessive phosphorylation of tau protein, therefore, the compound provided by the invention can be effectively used for preventing or treating a degenerative encephalopathy (neurogenerative brain disease), and can be used for preventing or treating the neurogenerative brain disease (neurogenerative brain disease).

This invention provides a ready-to-drink milk tea based on a ternary complex stabilized with κ-casein genotype and its preparation method, belonging to the field of dairy processing technology. It includes a ternary complex of casein micelles containing AA genotype κ-casein, epigallocatechin gallate, and fructose. The preparation of the ready-to-drink milk tea includes the following steps: S1: raw material screening and pretreatment; S2: preparation of the ternary complex; S3: blending and processing of the ready-to-drink milk tea. By screening AA genotype κ-casein raw milk and using a specific sequence of first compounding EGCG and then grafting fructose, a casein micelle-EGCG-fructose ternary complex with uniform structure and controllable particle size is constructed. Fructose is further grafted onto the surface of the complex through glycosylation, effectively masking the excessive binding sites of proteins and polyphenols, significantly inhibiting the formation of insoluble aggregates, thereby maintaining excellent colloidal stability of the product during its shelf life.

The present invention relates to a T7 RNA polymerase mutant and its application. Specifically, the present invention discloses a T7 RNA polymerase mutant, which has at least one amino acid mutation at a site corresponding to the wild-type T7 RNA polymerase selected from the group consisting of: position 44, position 45, position 46, position 172, position 389, position 425, position 441, position 632, position 643, position 754, and position 789; the numbering of the mutation sites is based on the sequence shown in SEQ ID NO:1, and the mutation results in a significant reduction in the by-product dsRNA produced during the process of the enzyme synthesizing mRNA, and at the same time reduces the production of RNA aggregates.

To provide a simple, high-resolution method of isolating and quantifying proteins, in particular antibody drugs and aggregates thereof, and suspended nanoparticles using the SEC (Size Exclusion Chromatography) method.SOLUTION: A size exclusion chromatography method is provided, involving analyzing nanoparticles with diameters in a range of 10 nm to 150 nm and proteins in an aqueous eluent containing one or more non-ionic surfactants.SELECTED DRAWING: Figure 11

Disclosed is a microfluidic device for mechanically splitting, in particular for aiding the enzymatic cleaving, of three-dimensional agglomerates into individual structures and / or agglomerate fragments, having a first fluidic connection and a second fluidic connection and at least one first microfluidic channel arranged between the first and the second fluidic connection, wherein the first microfluidic channel has at least one first retaining structure at which three-dimensional agglomerates can be mechanically split by means of friction, and wherein the at least one first retaining structure is positioned in the at least one first microfluidic channel such that unsplit three-dimensional agglomerates cannot pass any further through the microfluidic channel toward the second fluidic connection.