78 results about "Alpha globulin" patented technology

The present disclosure provides genetically modified iPSC-derived γδT cells and their precursors. A double genomic disruption in the suppressor of cytokine signaling 1 (SOCS1) gene and the cytokine-inducible sh2-containing protein (CISH) gene are provided, as is a triple genomic disruption in genes for SOCS1, CISH, and Bcl-2 interacting mediator of cell death (BIM), as is a quadruple genomic disruption in genes for SOCS1, CISH, BIM, and cell surface death receptor (FAS), as is a quintuple genomic disruption in genes for SOCS1, CISH, BIM, β-2-Microglobulin (B2M), and class II transactivator (CITTA), as is a sextuple genomic disruption in genes for SOCS1, CISH, BIM, B2M, CITTA, and FAS. Also provided is genetically modified iPSC-derived γδT cells and their precursors with improved proliferation and tumor killing activity. Also provided are genetically modified iPSC-derived γδT cells and their precursors further comprising CD19 CAR. The present disclosure further provides methods making and using such cells, as well as gene editing systems.

The invention relates to bacillus subtilis for expressing bovine-derived beta-lactoglobulin and a construction method of the bacillus subtilis, and belongs to the technical field of microorganisms. According to the bacillus subtilis provided by the invention, bacillus subtilis BSF01 is used as a host, a constitutive promoter P566 is used for heterologous expression of a bovine-derived beta-lactoglobulin coding gene optimized by a codon, the yield of beta-lactoglobulin obtained by shake flask fermentation for 30 hours reaches 0.37 g / L, the yield of beta-lactoglobulin obtained by 3L fermentation tank fermentation for 44 hours reaches 3.06 g / L, the production intensity is 0.07 g / L / h, and the production cost is low. The bovine-derived beta-lactoglobulin is efficiently and insolubly expressed in a food safety level strain, the food industrial application of the beta-lactoglobulin is promoted, and the problems of food safety and excessive glycosylation possibly existing in heterologous expression of the beta-lactoglobulin in the prior art are solved.

The present disclosure provides genetically modified iPSC-derived γδT cells and their precursors. A double genomic disruption in the suppressor of cytokine signaling 1 (SOCS1) gene and the cytokine-inducible sh2-containing protein (CISH) gene are provided, as is a triple genomic disruption in genes for SOCS1, CISH, and Bcl-2 interacting mediator of cell death (BIM), as is a quadruple genomic disruption in genes for SOCS1, CISH, BIM, and cell surface death receptor (FAS), as is a quintuple genomic disruption in genes for SOCS1, CISH, BIM, β-2-Microglobulin (B2M), and class II transactivator (CIITA), as is a sextuple genomic disruption in genes for SOCS1, CISH, BIM, B2M, CIITA, and FAS. Also provided is genetically modified iPSC-derived γδT cells and their precursors with improved proliferation and tumor killing activity. Also provided are genetically modified iPSC-derived γδT cells and their precursors further comprising CD19 CAR. The present disclosure further provides methods making and using such cells, as well as gene editing systems.

The invention relates to a T7RNA polymerase-guided bacillus subtilis cytosine base editor and application thereof, and belongs to the technical field of gene editing. A T7RNAP guided cytosine base editor is developed in bacillus subtilis, four kinds of cytidine deaminase from different sources are selected to be fused with T7RNAP, the cytidine deaminase is fused at the N end of the T7RNAP, and a fusion body with the highest mutation activity is obtained through screening; the cytosine base editor is used for evolving a global transcriptional regulatory factor CodY, in-situ evolution of genome protein is achieved, and the expression level of bovine-derived beta-lactoglobulin (beta-Lg) is improved. According to the cytosine base editor, the operable range of the cytosine base editor on a genome is widened, multi-site base (C-T) editing can be realized, and an editing window is large.

The present invention relates to compositions and methods for generating a modified T cell with a nucleic acid capable of downregulating endogenous gene expression selected from the group consisting of TCR α chain, TCR β chain, beta-2 microglobulin, a HLA molecule, CTLA-4, PD1, and FAS and further comprising a nucleic acid encoding a modified T cell receptor (TCR) comprising affinity for a surface antigen on a target cell or an electroporated nucleic acid encoding a chimeric antigen receptor (CAR). Also included are methods and pharmaceutical compositions comprising the modified T cell for adoptive therapy and treating a condition, such as an autoimmune disease.

Described herein are methods, assays and techniques for detecting and / or measuring anti-drug antibodies that bind to a protein, polypeptide or other compound or molecule that comprises at least one immunoglobulin variable domain with an exposed C-terminal region.

The present invention relates to compositions and methods for generating a modified T cell with a nucleic acid capable of downregulating endogenous gene expression selected from the group consisting of TCR α chain, TCR β chain, beta-2 microglobulin and FAS further comprising a nucleic acid encoding a modified T cell receptor (TCR) comprising affinity for a surface antigen on a target cell or an electroporated nucleic acid encoding a chimeric antigen receptor (CAR). Also included are methods and pharmaceutical compositions comprising the modified T cell for adoptive therapy and treating a condition, such as an autoimmune disease.

The invention relates to a construction method, an evaluation method and application of an inflammatory nephropathy animal model, and relates to the technical field of nephropathy animal model construction. The construction method comprises the steps that a CRIPSR / Cas9 system is adopted to shear a first targeting site on an Smu region of a mouse immune globulin gene, and a second targeting site on an Sgamma2c region of the mouse immune globulin gene is sheared, so that a base sequence between the first targeting site and the second targeting site is knocked out, and the inflammatory nephropathy animal model is obtained. The application comprises an application of the inflammatory nephropathy animal model constructed by the construction method in screening drugs for treating inflammatory nephropathy and an application in researching a molecular mechanism of occurrence and development of inflammatory nephropathy.

Phospholamban (PLN) is a critical regulator of calcium cyclin and contractility in the heart. The deletion of Arginine 14 of the phospholamban gene (R14del) is associated with the pathogenesis of an inherited form of cardiomyopathy with prominent arrhythmias. Although the genetic etiology is well defined, there are currently no therapies for this rare disease. This disclosure provides an allele-specific silencing approach by interfering RNA (RNAi) to reduce the expression levels of the R14del allele of the PLN gene.

The present disclosure describes a genetically modified microbial host cell expressing one or more heterologous genes encoding a modified beta-lactoglobulin (BLG), thereby producing the said modified BLG, wherein the modified BLG comprises at least one substitution of a non-essential and / or non-branched amino acid with an essential and / or branched amino acid compared to a parent unmodified BLG.

The invention discloses goat milk with hypoglycemic activity and a preparation method thereof, and belongs to the technical field of enzyme engineering. The goat milk is used as a raw material, enzymolysis goat milk with alpha-G inhibitory activity is obtained through compound protease hydrolysis, it is found that the enzymolysis goat milk has hypoglycemic activity, and the goat milk powder with the hypoglycemic activity is further prepared through spray drying. The alpha-G inhibitory peptides in the enzymolysis goat milk are separated and identified, 20 alpha-G inhibitory peptides are found from components with the highest alpha-G inhibition rate, the molecular weight of the alpha-G inhibitory peptides is 377-962 Da, and the alpha-G inhibitory peptides are mainly derived from beta-casein, alpha S1-casein, alpha S2-casein, kappa-casein, beta-lactoglobulin, lactoglobulin and osteopontin of the goat milk. The alpha-G inhibitory peptide is prepared by hydrolyzing the goat milk through the compound enzyme, the amino acid sequence of the alpha-G inhibitory peptide is separated and identified, the goat milk with hypoglycemic activity is developed, and theoretical basis and technical support are provided for subsequent development of hypoglycemic dairy products.

The present disclosure provides an engineered population of natural killer cells wherein the NK cells express at least one polypeptide selected from the group consisting of human leukocyte antigen E, human leukocyte antigen F, and human leukocyte antigen G. The NK cell comprises a genetically modified disruption of one or more copies of an endogenous beta-2 microglobulin and a genetically modified disruption of one or more copies of a human leukocyte antigen class II-related gene, the human leukocyte antigen class II-related gene is selected from a protein containing regulatory factor X-related ankyrin, a regulatory factor 5, a regulatory factor X-related protein and a class II trans-activator. Also provided are a method of producing human pluripotent stem cell-derived engineered natural killer cells without feeder cells, and a method of treating a disease or condition in a subject by administering the NK cells to the subject.

The invention relates autonomous VH domains (aVH) with cysteines in positions 52a and 71 or in positions 33 and 52 in order to stabilize the autonomous VH domains. Said cysteines are capable of forming a disulfide bond and / or form a disulfide bond under suitable conditions. The invention further relates to aVH libraries.

A continuous directed evolution platform in human B cell lines (CODE-HB) that recruits and repurposes the inherent B cell somatic hypermutation (SHM) mechanisms to rapidly evolve proteins is described. This approach uses stable, non-immunoglobulin loci within the genomes of human B cell lines for integration of a heterologous gene, such as a gene encoding an antibody or antibody fragment. A B-cell surface display platform for displaying fragment antigen binding domains (Fab) of antibodies is also described, which adapts the CODE-HB platform to rapidly evolve antibody fragments in a continuous manner. Plasmids and kits for carrying out these methods are also described.

Disclosed herein are cell culture media comprising a plant protein composition, plant protein compositions, methods of preparing plant protein compositions, cell culture media supplements, and method of using the same, e.g., methods of expanding or differentiating cells. The methods of preparing the protein compositions comprise substantially removing globulins in the plant protein composition, e.g., by reducing the pH of and / or filtering the plant protein composition. The resulting plant protein compositions are used to generate increased yield in cell culture while also maintaining cell growth utility. The plant protein compositions may be used in serum-free culture media and methods of using serum-free culture media, including for expansion of cells.

The invention discloses a multi-step enzymolysis desensitization process for preparing low-sensitization beta-lactoglobulin peptide and application, and belongs to the technical field of food safety detection. According to the method disclosed by the invention, the anaphylaxis of the beta-lactoglobulin can be obviously reduced, and the antigen reduction rates are 62.46% (the combination of pepsin and papain) and 71.81% (the combination of bromelain and pepsin) respectively. The low-anaphylaxis beta-lactoglobulin peptide can effectively maintain the spleen index and the body temperature of an allergic model mouse at the physiological level, reduce the level of IgE (Immunoglobulin E) and improve the protective barrier of intestinal tracts. On the basis, the method can be effectively applied to development of food industry and functional food, meanwhile, technical support is provided for development of dairy product raw materials and products with higher safety, and wide industrial application prospects are shown.

The present disclosure provides compositions (e.g., pharmaceutical compositions) for delivery of anti-HIV antibody agents and related technologies (e.g., components thereof and / or methods relating thereto). Among other things, the present disclosure provides polyribonucleotides encoding an immunoglobulin chain of an anti-HIV antibody agent.

The invention relates to regions within the synaptogyrin-3 RNA sequence that are targetable by oligonucleotide inhibitors such as antisense oligonucleotides. In particular, these synaptogyrin-3 inhibitors are provided for use as a medicament in general, and for treating or inhibiting progression of tauopathies or symptoms of tauopathies.

The present invention relates to antigen-binding proteins, such as antibodies, that bind to leukocyte immunoglobulin-like receptor subfamily B1 (LILRB1) and LILRB2 without binding or with significantly lower affinity to leukocyte immunoglobulin-like receptor subfamily A (LILRA), which can also inhibit the interaction between LILRB1 and / or LILRB2 and a native ligand of the LILRB receptor (interacting protein, such as HLA-G) on an immune cell, such as LILRB1 and LILRB2. And the inhibition of the interaction can reduce the inhibition of immune cells, thereby supporting the anti-infection and anti-tumor immune response of subjects suffering from the disease. In particular, the present invention provides products, compositions and methods for treating disease using antigen binding proteins of LILRB1 and / or LILRB2, particularly antigen binding proteins that preferably specifically bind to LILRB1 and LILRB2, such as antigen binding proteins that further do not bind or bind with lower affinity to one or more LILRA receptor proteins (e.g., LILRA1 and / or LILRA3). Also provided are methods of using LILRB1 and / or LILRB2 antigen binding proteins, such as antibodies that bind to LILRB1 and / or LILRB2, to reduce immunosuppression of cells involved in a cell-mediated immune response and / or to treat infectious and / or proliferative diseases, as well as certain related aspects, including methods of detection, diagnosis, and screening.

The application relates to a soybean polypeptide and a preparation method and application thereof. The preparation method of the soybean polypeptide comprises the following steps: performing an enzymolysis reaction on soybean protein isolate by using a protease, centrifuging and collecting supernatant, performing ultrasonic treatment on the supernatant, and obtaining the soybean polypeptide. The preparation method of the soybean polypeptide utilizes the protease to perform the enzymolysis on the soybean protein isolate, can efficiently degrade the soybean protein, performs the ultrasonic treatment on the supernatant, can further promote the degradation of a beta-conglycin alpha subunit anti-enzymolysis peptide segment, and obtains a high-quality product which is clear and transparent.

This disclosure relates to bicistronic polypeptide constructs for use in allogeneic gene therapy, such as CAR-T cell therapy. A bicistronic construct comprises a first polynucleotide encoding a therapeutic molecule (e.g., CAR-T or antibody) and a second polynucleotide encoding an immune surveillance masking molecule (ISMM). The ISMM includes a non-functional version of a protein knockout, such as a human leukocyte antigen E genetically fused to a fragment, by insertion of a bicistronic construct, such as beta-2 microglobulin or B2M. Also provided are vectors comprising bicistronic constructs, cells (e.g., CAR-T cells), and methods of use. Kits and manufacturing articles are also provided. This disclosure also provides four novel insertion sites that may be used to insert expression constructs into the B2M gene.

The present disclosure provides methods of determining whether a subject treated for hypertension should continue hypertension treatment. In exemplary embodiments, the method comprises measuring the level of at least two of the following in a urine sample obtained from the subject: (i) Alpha-1 microglobulin (aim); (ii) kidney injury molecule (KIM-1); and (iii) Chitinase-3-like protein (YKL-40); wherein the subject should continue the hypertension treatment, when the levels are decreased or unchanged, relative to a control level, and wherein the subject should discontinue or decrease the hypertension treatment, when the levels are increased, relative to a control level. Related methods, kits, assay systems, systems comprising machine readable instructions, computer-readable storage media, and methods implemented by a processor in a computer are furthermore provided herein.

The present disclosure relates to bicistronic polypeptide constructs for use in allogeneic gene therapy, such as CAR-T cell therapy. The bicistronic constructs comprise a first polynucleotide encoding a therapeutic molecule (e.g., CAR-T or an antibody) and a second polynucleotide encoding an immune surveillance masking molecule (ISMM). The ISMs comprise a human leukocyte antigen-E genetically fused to a non-functional form, such as a fragment, of a protein, such as beta-2 microglobulin or B2M, which is knocked out by insertion of the bicistronic construct. Also provided are vectors, cells (e.g., CAR-T cells) comprising the bicistronic constructs and methods of use. Kits and articles of manufacture are also provided. The present disclosure also provides four new insertion sites that can be used to insert an expression construct into the B2M gene.

The purpose of the present invention is to provide, as a platform technique that may serve as preparation for pandemics, a rapid antibody production technique in which a non-human animal having a human antibody gene is used. More specifically, the purpose of the present invention is to provide an immunization method with which it is possible to induce, in a short period of time, a high antigen-binding ability of an antibody or a high antibody titer of an antiserum, and a method for producing a human antibody / antiserum with which it is possible to rapidly produce a wide range of neutralizing antibodies.　(1) An immunization method for rapidly inducing a human monoclonal antibody having a high ability to bind to a desired antigen or a human polyclonal antibody having a high antibody titer, the method comprising a step for immunizing a non-human animal a plurality of times with a desired antigen or a nucleic acid encoding the antigen within 30 days from the first immunization, the non-human animal having a human antibody gene or locus, and the non-human animal being such that an endogenous gene or locus of the non-human animal corresponding to the human antibody gene or locus is disrupted or deleted, or mutated so as to result in a loss of expression or low expression. (2) A method for producing a human antibody against a desired antigen using a non-human animal, the method comprising: an immunization step for immunizing the non-human animal with the antigen or a nucleic acid encoding the antigen; a human immunoglobulin-positive B cell isolation step for isolating B cells that are human immunoglobulin-positive from a tissue of the immunized non-human animal; an antibody base sequence acquisition step for acquiring the base sequences of antibody light-chain mRNA-derived cDNA and antibody heavy-chain mRNA-derived cDNA prepared from the isolated B cells; and an antibody production step for producing an antibody on the basis of the acquired antibody base sequence, the non-h

An oligosaccharide composition for use in the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions. The composition comprises oligosaccharide compounds, for example galactooligosaccharide compounds, which includes: (a) at least 8 wt% Gal-(β1-3)-Gal-(β1-4)-Xa; (b) at least 3 wt% Gal-(β1-3)-Gal-(β1-3)-Xb; and (c) at least 5wt% Gal-(β1-3)-Gal-(β1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb and Xc are each independently selected from monosaccharides. These compositions contain relatively high amounts of the oligosaccharide compounds (a), (b) and (c) and a relatively high amount of β1-3 Gal-Gal linkages, compared to known oligosaccharide compositions. These particular features of the composition are believed to provide benefits to the health of a subject during and / or after athletic activity, for example reducing episodes of URS and GI discomfort and / or damage. A method of preparing said composition and the use of said composition as a dietary supplement or a medicament are also disclosed. Oligosachharide compositions for use in and methods of reducing plasma I-FABP and / or increasing salivary immunoglobulin A (sIgA) during and / or after athletic activity in extreme environmental conditions by administering the oligosaccharide composition according to the present invention are also disclosed.

Polypeptides comprising a fragment of an N-terminal extracellular domain (ECD) of TSHR wherein said ECD consists of SEQ ID NO: 1 and comprising at least one mutation selected from P7S, H12L, RISE, V19L, T36L, S64Y, I65F, V83I, R92K, Y96S, Y96E, Y96R, D131Q, D131N, V149K, S171D, G174A, V195D, K198Q, L210Y, V218I, I233K, I233K and V149K, are provided. Compositions comprising the polypeptide, and nucleic acid molecules encoding the polypeptide are also provided as are methods of treating Graves' Disease.

A genetically modified mouse is provided, wherein the mouse is incapable of rearranging and expressing an endogenous mouse immunoglobulin light chain variable sequence, wherein the mouse expresses only one or two human light chain variable domains encoded by human immunoglobulin sequences operably linked to the mouse kappa (κ) constant gene at the endogenous mouse κ locus, wherein the mouse expresses a reverse chimeric antibody having a light chain variable domain derived from one of only two human light chain variable region gene segments and a mouse κ constant domain, and a human heavy chain variable domain and a mouse heavy chain constant domain, from an endogenous mouse heavy chain locus. Bispecific epitope-binding proteins that are fully human are provided, comprising two different heavy chains that associate with an identical light chain that comprises a variable domain derived from one of two different human light chain variable region gene segments.

The present invention provides a chimeric protein comprising a first polypeptide which comprises a FVIII protein and a first Ig constant region or a portion thereof and a second polypeptide which comprises a VWF protein comprising the D′ domain and D3 domain of VWF, a XTEN sequence having less than 288 amino acids in length, and a second Ig constant region or a portion thereof, wherein the first polypeptide and the second polypeptide are associated with each other. The invention also includes nucleotides, vectors, host cells, methods of using the chimeric proteins.

The disclosure provides nucleic acid constructs comprising a transmembrane reporter cassette encoding an affinity tag, a transmembrane (TM) domain and a fluorescent reporter protein. In embodiments, the nucleic acid constructs are inserted in a safe harbor locus or an immunoglobulin constant domain locus of in a cell of a non-human mammal. In embodiments, when the transmembrane reporter cassette is expressed in the cell, the affinity tag is displayed on a surface of the cell while the fluorescent reporter protein is located inside the cell membrane. The presence of the affinity tag and the fluorescent reporter protein allow for identification, sorting and / or isolation of cells expressing the nucleic acid constructs. The disclosure also provides embodiments of methods of modifying cells and non-human organisms with the nucleic acid constructs, along with embodiments of cells and non-human organisms produced using the disclosed methods.

Provided herein are engineered MHC molecules compositions for treatment of a disease or disorder. The compositions described herein include an engineered MHC heavy chain; an engineered beta 2-microglobulin (B2m) protein; and / or an MHC class I molecule complex that have been modified to have increased binding affinity to cell coreceptors, such as CD8, and also have increased internalization in immune cells relative to an otherwise comparable MHC class I heavy chain, B2m protein, or MHC class I molecule complex. Various protein constructs and pharmaceutical compositions of the engineered MHC molecules are provided. Methods of utilizing the protein constructs and pharmaceutical compositions of the modified MHC molecules are also provided.