121 results about "Alpha globulin" patented technology

The invention belongs to the technical field of gene engineering, and particularly relates to a strain for efficiently expressing beta-lactoglobulin as well as a construction method and application of the strain. By utilizing the beta-lactoglobulin expression vector disclosed by the invention, beta-lactoglobulin is guided to be secreted out of a host cell by an exogenous signal peptide, and efficient secretory expression of the beta-lactoglobulin in the host cell is realized by integrating a multi-copy expression cassette through a genome and co-expressing ATP enzyme Ssa4 participating in protein folding and coping with pressure; the amino terminal and the carboxyl terminal of the secreted and expressed beta-lactoglobulin do not contain redundant amino acids, and do not contain animal-derived components. Meanwhile, the invention provides a construction method and a fermentation culture method of the engineering strain, compared with a single-copy genetically engineered strain, the expression quantity of the genetically engineered strain in shake-flask fermentation is increased by 2.47 times, and the genetically engineered strain has a good industrial application prospect.

The invention discloses a construction method and application of a mouse for expressing a heavy-chain antibody IgG1, and relates to the technical field of biology. The mouse capable of expressing the heavy-chain antibody IgG1 is constructed by the method provided by the invention, does not contain an immunoglobulin light-chain gene and a gamma1-CH1 exon, can generate the IgG1 type heavy-chain antibody, and is relatively high in expression quantity and strong in antigen affinity. The invention also provides an application of a mouse expressing the heavy-chain antibody IgG1 in production of a nano antibody. The invention provides a new thought and method for further modifying and transforming transgenic mice expressing more heavy-chain antibodies, and effectively solves the problems of low heavy-chain antibody expression quantity, weak antigen affinity and weak immune response of the existing mice.

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 antigen binding proteins, such as antibodies, that bind to both leukocyte immunoglobulin-like receptor subfamily B1 (LILRBI) and LILRB2 while not binding to, or binding with significantly less affinity to, leukocyte immunoglobulin-like receptor subfamily A (LILRA), which can also inhibit the interaction between LILRB1 and / or LILRB2 and a natural ligand of LILRB receptors (interacting proteins, such as HLA-G) on immune cells and the inhibition of such interaction can reduce immune cell suppression and thereby support anti-infection and anti-tumour immune responses in a subject suffering from such diseases. In particular, the invention provides products, compositions and methods for treating diseases using antigen binding proteins of LILRB1 and / or LILRB2, especially antigen binding proteins which while, preferably specifically, binding to LILRB1 and LILRB2, such as antigen binding proteins that further do not bind to, or bind with less affinity to, one or more LILRA receptor proteins (such as LILRA1 and / or LILRA3). Also provided are methods of reducing the immune suppression of cells involved with a cell-mediated immune response, and / or methods for treating infective- and / or proliferative diseases, using an LILRB1 and / or LILRB2 antigen binding protein such as an antibody binding to both LILRB1 and / or LILRB2, as well as certain related aspects including detection, diagnostic and screening methods.

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.

Compositions and methods are disclosed for uniquely tagging each rearranged gene segment that encodes a T cell receptor (TCR) and / or an immunoglobulin (Ig), in a DNA (or mRNA or cDNA reverse transcribed therefrom) sample from lymphoid cells. These and related embodiments permit accurate, high throughput quantification of distinct TCR and / or Ig encoding sequences. Also provided are compositions and methods for quantitatively sequencing the genes that encode both chains of a TCR or Ig heterodimer in a single cell, for example, to characterize the degree of T or B cell clonality in a sample.

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.

The invention relates to a method for quantifying haematopoietic stem and progenitor cells (HSPCs), in which method at least one sample comprising cells, which each comprise at least one nucleic acid molecule, is provided, and the methylation level of at least one CpG dinucleotide within at least one specific region of the nucleic acid molecule is determined. The determined methylation level of the CpG dinucleotide then indicates the proportion of haematopoietic stem and progenitor cells in the sample. According to the invention, the specific region is selected from the group consisting of the following genes: serine / threonine kinase 17a (STK17A); myosin ID (MYOID); nuclear body protein SP140 (SP140); CD48 molecule (CD48); and nuclear factor of activated T-cells 1 (NFATC1). The predictions made using the signature according to the invention correlate with the flow cytometric analysis of CD34+ counts in mobilised peripheral blood.

The invention relates to a chimeric antigen-receptor polypeptide heterodimer comprising two polypeptides, wherein the first contains an extracellular part of the major histocompatibility complex I alpha chain and the second contains a β2-microglobulin domain, or the first contains an extracellular part of the major histocompatibility complex Il alpha chain and the second contains a major histocompatibility complex Il beta chain. One of the polypeptides further contains a transmembrane domain, a hinge region and an intracellular domain of the T cell receptor alpha chain and the other one contains a transmembrane domain, a hinge region and an intracellular domain of the T cell receptor beta chain, and additionally an antigen-peptide covalently linked to said extracellular MHC domain. The invention further relates to a method for the identification of a TCR recognizable peptide sequence making use of the heterodimer of the invention.

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.

Improved sample preparation methods for detecting and / or quantifying host cell proteins in a sample are provided. The methods include contacting a sample with a solid support including an immunoglobulin binding protein at a pH of about 8-10 to produce a sample including the antibody or antibody fragment bound to the solid support. The methods also include contacting the sample including the antibody or antibody fragment bound to the solid support with a protease agent to produce partially digested antibody and target proteins and separating the sample into a first fraction including the antibody or antibody fragment bound to the solid support, and a second fraction including a supernatant including the partially digested target proteins. The methods also include processing the supernatant and detecting the one or more target proteins, for example using mass spectrometry. Compositions and kits for detecting host cell proteins are also provided.

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.