260 results about "Aggresome" patented technology

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 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.

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 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 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).

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).

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.

The invention belongs to the technical field of plant protein extraction, and particularly relates to high-foamability edible rapeseed protein as well as a preparation method and application thereof. According to the method, a gradient acidic-neutral pH circulating treatment technology is utilized, and membrane separation and physical field modification technologies are coupled under gradient pH control, so that the structural characteristics of the rapeseed protein are regulated and controlled in order. Primary acidity is controlled under a weak acid condition (pH is 5.0-7.0) to cooperate with an ultrafiltration step concentration process to obtain a high-concentration rapeseed protein solution (the protein concentration is greater than or equal to 6%); the secondary acidity control is to regulate and control a rapeseed protein structure under an acidic condition (pH is 2.0-4.0), couple ultrasonic, infrared and other physical field treatments, and penetrate into the internal region of the protein structure through cavitation, shearing, heat effect and other actions, so that the surface charge, hydrophobicity and other structural characteristics of the rapeseed protein structure are changed, and the interaction between polyphenol and protein is influenced; finally, the pH is circulated to be neutral, the protein is reassembled to form a controllable aggregate, and finally the rapeseed protein is endowed with the high-foam characteristic and the good color and luster.

A method for determining the presence of soluble, misfolded protein in or on the eye of a subject is described. The method includes contacting the eye of the subject with a monomeric protein to form an incubation mixture; incubating the incubation mixture to form a misfolded protein aggregate from the monomeric protein; and determining if a detectable amount of misfolded and / or aggregated protein is present in or on the eye; wherein detection of misfolded and / or aggregated protein indicates the presence of soluble, misfolded protein in the eye. Use of the method for diagnosing disease associated with protein misfolding in a subject is also described.

The invention provides a pyridine derivative and a preparation method and application thereof, a Tau protein aggregate probe and a preparation method and application thereof, and relates to the technical field of ligands of protein aggregates. The pyridine derivative provided by the invention has an indole combined quinoline structure, has high selectivity, high specificity and high affinity to Tau protein, can be used as a selective ligand of a Tau protein aggregate, provides a diagnostic tool and a treatment strategy for neurodegenerative diseases such as Alzheimer's disease, and has broad application prospects. The method has potential value for early diagnosis, disease progress monitoring and treatment effect evaluation of neurodegenerative diseases.

An object of the present invention is to provide a cell aggregate-inducing peptide, a cell aggregate-forming agent containing the same, and a method for forming a cell aggregate using the same.SOLUTION: A cell aggregate-inducing peptide represented by General Formula (1), having hydroxypipecolic acid and lysine as constituent repeating units. (HPA-Lys) n. (1) [In the general formula (1), HPA represents hydroxypipecolic acid, Lys represents lysine, and n is an integer of 4 or more and 30 or less.]. ] SELECTED DRAWING: None

The present invention discloses a method for monitoring the amyloid fibrillization process of lysozyme based on cluster luminescence. The method utilizes the property that lysozyme itself can emit fluorescence in an aggregated state, and the intensity of the fluorescence changes with the change of the aggregation state of lysozyme, thereby achieving the purpose of monitoring the amyloid fibrillization process of lysozyme. The method only needs to perform fluorescence detection on the fluorescence of the protein solution that can form amyloid fiber aggregates, without the introduction of exogenous fluorescent probes. The method is simple and has lower cost. The method can fully present the overall process of amyloid fibrillization and has the advantage of high sensitivity, especially high sensitivity to the early stages of amyloid fibrillization.

This invention discloses a method for preparing a secondary antibody and its application, belonging to the fields of biomedicine and bioengineering technology. The invention specifically designs an efficient multidimensional chromatographic purification strategy, sequentially passing the serum to be purified through four chromatographic columns: affinity capture (recovering IgG target molecules and removing most plasma protein impurities); antigen affinity enrichment (further enriching antibody subpopulations with high affinity and specificity to the target antigen, reducing the coexistence of non-specific subpopulations); tandem cross-adsorption (removing antibody subpopulations that cross-react to non-target species and reducing potential non-specific binding); and size exclusion / gel filtration (removing high molecular weight aggregates and low molecular weight residues, and achieving final buffer replacement and sample homogenization). The secondary antibody prepared by this invention exhibits significantly better sensitivity, specificity, and batch-to-batch consistency than existing technologies, with sensitivity improved by approximately 57% and specificity greatly enhanced compared to conventional techniques.

The invention relates to a method of detecting cancer in a subject based on the level of p53 protein aggregates in a body fluid sample from the subject. The invention also relates to corresponding methods of determining the risk of cancer in a subject, monitoring the progression or onset of cancer, and / or determining the efficacy of a therapeutic intervention for treating cancer in a subject. The invention further relates to kits for use said methods.

The invention belongs to the technical field of antibody purification, and relates to a method for removing impurities in a sample containing a trispecific antibody. According to the method provided by the invention, impurities, especially aggregates and fragments, can be well removed, and the purity detected by molecular exclusion chromatography-high performance liquid chromatography (SEC-HPLC) is increased from about 74% to 98% or above; the purity detected by non-reduction method lauryl sodium sulfate capillary electrophoresis (NR-CE-SDS) is improved from about 76% to 93% or above. Besides, the method provided by the invention can control the content of host cell protein at a lower level, greatly improves the quality of a tri-specific antibody product, and has the advantages of stable process and easiness in large-scale production.

The present invention relates to compounds which are suitable for imaging TDP-43 (Transactive response (TAR) DNA binding protein 43 kDa) aggregates. The compounds can be used, for example, for diagnosing a disease, disorder or abnormality associated with TDP-43 aggregates or a TDP-43 proteinopathy, such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE).

Disclosed are compositions and methods for treating Alzheimer's disease or for use in treating Alzheimer's disease. Also disclosed are compositions and methods for treating or for use in treating a neurodegenerative disorder characterized by the presence of tau protein aggregates. Furthermore, disclosed are compositions and methods for reducing tau protein aggregates or for use in reducing tau protein aggregates.

Bipartite molecules comprising a peptide affinity moiety and at least one charged moiety and uses thereof in reducing formation of abnormal protein aggregate and treating diseases associated with such abnormal protein aggregate, including neurodegenerative disease characterized by formation of protein aggregates.