225 results about "Homomeric" patented technology

This disclosure relates to modulators of liver receptor homologue 1 (LRH-1) and methods of managing disease and conditions related thereto. In certain examples, modulators are derivatives of hexahydropental ene. In certain examples, this disclosure relates to methods of treating or preventing cancer, diabetes, or cardiovascular disease by administering an effective amount of a hexahydropentalene derivative disclosed herein.

A microbial gene editing scheme automatic design method, system and storage medium; the method comprises: selecting a design object for different types of strains, the design object is bacteria or fungi; after determining the target gene, obtaining the target gene information from the NCBI database; the design scheme of bacteria comprises the following steps: determining the gRNA design region; selecting the optimal gRNA sequence; doing sequence complexity and GC content analysis; the design scheme of fungi uses a frameshift scheme: the gRNA of the frameshift scheme is set at any position not overlapping with other genes after the start codon in the gene; select gRNA sequence in gRNA design region, select the optimal gRNA sequence; design two pairs of four primer sequences for homologous arm identification primer; this scheme can replace the complicated and time-consuming manual scheme, save a lot of time, solve the problem of high cost in the design of the best site and the design of sgRNA sequence scheme of artificial gene knockout.

This invention relates to monoclonal antibodies for detecting A35R protein and their applications. This invention screened six antibodies, including antibody 4E7, antibody 11G12, antibody 6F10, antibody 6C11, antibody 18C3, and antibody 23A7. Specifically, this invention discloses the amino acid sequences of the heavy chain variable region and the light chain variable region of the above antibodies, as well as the amino acid sequences of their complementarity-determining regions and framework regions. Antibodies 4E7 and 11G12 can bind not only to the A35R-MPXV protein but also to its homologs A35R-CPXV, A35R-VTT8, and A35R-Variola. Antibodies 6F10, 6C11, 23A7, and 18C3 can specifically recognize the A35R-MPXV protein. The monoclonal antibodies described above all exhibit high binding capacity to the A35R protein, making them suitable for the sensitive and specific detection and prevention of monkeypox virus A35R protein. They can also be used clinically for the diagnosis and treatment of monkeypox virus infection-related diseases.

The present application relates to a kind of calcium peptide chelate based on defatted sheep bone powder homologous recombination and its preparation method and application, preparation method, including the following steps, defatted sheep bone powder is mixed with water, flavourzyme is added to carry out enzymolysis, enzyme is inactivated after enzymolysis, and the enzymatic hydrolysate containing bone-derived peptide is obtained;Lactic acid is added in enzymatic hydrolysate and is hydrolyzed, so that calcium ion is dissolved, and the mixed solution containing bone-derived peptide and calcium ion is obtained;Mixed solution is carried out chelation under neutral condition, after reaction, aftertreatment is carried out, and calcium peptide chelate is obtained;Calcium peptide chelate prepared according to the above preparation method is used as salty taste enhancer, salt-reducing auxiliary agent or flavor enhancer, and its application in food.The present application has the advantages of homologous resource recombination, improves chelation rate, raw material utilization rate is high, realizes sheep bone by-product high value, process safety, can add chelate to clear soup base material, so as to reduce sodium, the effect of calcium supplement, salty seasoning.

This invention discloses a gene editing method and application for *Trichoderma reesei* based on a ribonucleoprotein complex. It aims to overcome the problems of low editing efficiency, easy generation of heterozygotes, and risk of exogenous DNA integration in *Trichoderma reesei* using plasmid-based CRISPR / Cas9 systems. This invention combines a dual-site cleavage strategy guided by double sgRNAs with direct RNP delivery. The method involves: designing two guide RNAs spaced 50-700 bp apart for the target gene, pre-assembling them with Cas9 protein in vitro to form an active RNP complex; delivering this complex along with exogenous donor DNA to *Trichoderma reesei* protoplasts. The exogenous donor DNA contains a left homologous arm, an editing sequence, and a right homologous arm, wherein the left and right homologous arms are homologous to the genomic sequences outside the dual cleavage sites on the target gene determined by the double sgRNAs, respectively; upon entering the cell, the RNP complex introduces dual-site cleavage at the target site, achieving precise editing under the guidance of the exogenous donor DNA.

The integration procedure provides different elements that require in vitro amplification of HSPCs, preferably for about 48 hours, in the presence of hematopoietic cytokines as well as UM171 and stem cell regenerative factor 1, and the introduction of i) a system (e.g., a CRISPR / Cas9 system) that generates DNA double-strand breaks (DSBs) upstream of the transcription start site of the target gene, and ii) the introduction of a donor matrix comprising cDNA with homologous arms on both sides (left [LHA] and right [RHA]).

The application discloses an African swine fever virus attenuated strain with I215L protein deletion, a live vaccine preparation method and application thereof, and belongs to the technical field of biotechnology, and particularly relates to an African swine fever virus attenuated strain with I215L protein deletion, a live vaccine preparation method and application thereof. The recombinant virus prepared by the application is an African swine fever virus I215L protein function deletion strain, the I215L partial gene is deleted, and the immunization of the weak strain with the gene deletion can achieve 100% immune protection effect on homologous II type ASFV and heterologous I / II type ASFV, and meanwhile, there is no residue in the body, so that the application has a wide application prospect.

This invention discloses a *Bacillus laterosporus* strain for the stable production of nonribosomal cyclic lipolipeptide and its construction method. The M1A gene in the Bogorol biosynthetic gene cluster is knocked out using CRISPR-Cas9 technology to block the Bogorol pathway, which competes with Brevicidine for substrates. Subsequently, the pMCCas9-S48 plasmid, which integrates S8 and S41 sgRNAs and their homologous arms as repair templates, is used to simultaneously knock out S8 and S41 family peptidase genes, preventing the expression of extracellular degradation enzymes. This invention also provides the application of the above strain in the preparation of nonribosomal cyclic lipolipeptide of Brevicidine and a method for preparing the nonribosomal cyclic lipolipeptide. This strain, through reducing metabolic competition and preventing product degradation, exhibits rapid cell growth, stable production of Brevicidine, and significantly reduced degradation rate, resulting in a 66.13% increase in fermentation yield compared to the unmodified strain. This invention solves the problems of degradation and unstable yield in the production of Brevicidine, provides an effective technical approach for the industrial production of Brevicidine, and provides important technical support for the development and application of novel antimicrobial peptide drugs.

This invention provides a high-throughput method for constructing dual sgRNA libraries and its applications. The method utilizes high-throughput microarray synthesis technology to prepare a set of DNA fragments containing multiple dual sgRNA expression cassettes in a single step. After amplification, these fragments are assembled with a target vector containing a first promoter and a second gRNA backbone sequence in a first round of directed assembly to obtain a preliminary recombinant plasmid set. Then, linearized enzyme digestion and homologous recombination technology are used to insert a fragment containing a transcription termination sequence and a complete second promoter to complete the construction of the dual sgRNA expression unit. Finally, transformation and amplification yield the dual sgRNA plasmid library. This invention avoids the high error rate and high cost of long-chain oligonucleotide synthesis by utilizing microarray synthesis and simplifies the operation process through two rounds of directed assembly, significantly improving the throughput, fidelity, and efficiency of library construction. It is applicable to the construction of genome-wide dual sgRNA libraries, providing an efficient and reliable technical platform for high-throughput gene function screening, drug target discovery, and gene interaction research based on CRISPR.

The application discloses a monoclonal antibody of a rice field eel Adam8a and a preparation method and application thereof, relates to the technical field of biological antibodies, and fills the research blank of the rice field eel Adam8a. The rice field eel Adam8a monoclonal antibody is high in specificity and titer, simple in preparation process, and controllable in cost, can be widely used for recognizing Adam8a homologous proteins in different fish ovary, and is suitable for being prepared into a fish ovary Adam8a protein detection kit, and is compared with the expression of the protein in different fish, so that the rice field eel Adam8a monoclonal antibody becomes a very convenient detection tool in the biological research of fish ovary development.

The application belongs to the cross field of virology and bioinformatics, and particularly relates to a virus identification model construction method and system based on capsid proteins. The method collects capsid protein sequence data and non-capsid protein sequence data, and trains a capsid protein identification model; obtains capsid protein sequences with known structures, structure information and hierarchical classification information, and identifies a few-sample category with a sample quantity lower than a preset threshold; generates supplementary data of the few-sample category through a protein sequence design model and screens the supplementary data from the collected capsid protein sequence data, predicts the three-dimensional structure of the sequence in the supplementary data, and together with the corresponding classification information, forms a capsid protein supplementary data set for training a capsid protein classification model. The application alleviates the problems of data imbalance caused by insufficient data of the few-sample category and high classification difficulty of remote homologous proteins caused by single feature extraction, and is helpful to realize efficient preliminary identification of viruses.

This invention discloses a methanogenic lyase homologous to PeiR lyase and its applications. The PeiR lyase protein, targeting the peptide bonds of the methanogenic cell wall, participates in the biological process of hydrolyzing the archaea cell wall, effectively killing methanogens and reducing methane production. Proteins homologous to this lyase possess potential methane-reducing potential. This invention utilizes a series of bioinformatics software to identify protein sequences encoded by methanogenic viruses from a large amount of rumen microbial virome sequencing data, and analyzes the structural homology between these proteins and PeiR. Ultimately, this invention successfully obtained a series of methanogenic lyases homologous to PeiR. To achieve the expression of these lyases, this invention designed multiple primers to synthesize the target sequences and successfully expressed them in a prokaryotic expression system. In vitro gas production experiments with the crude enzyme solution showed that these lyases are effective in reducing methane production.

The application discloses a kind of avian influenza and avian infectious bronchitis two-union recombinant subunit vaccine and its preparation method and application.The recombinant protein is by replacing the head domain of AIV HA protein with the RBD domain of IBV S protein, while adding GCN4, Trimer-tag trimer tag in sequence, the recombinant protein obtained, the recombinant protein is expressed in vitro using insect cells and prepared into subunit vaccine.The vaccine prepared by the application can produce high-level neutralizing antibodies against homologous and heterologous H9N2 subtype avian influenza virus after immunizing chicken population, while significantly reducing the virus discharge level and the histopathological changes caused, and can also induce high-level specific antibodies and neutralizing antibodies against QX subtype avian infectious bronchitis virus, effectively inhibit discharge, viral load, and reduce tissue lesions.The application does not depend on chicken embryo, and has low production cost and short cycle, and can simultaneously prevent avian influenza and avian infectious bronchitis.

A recombinant adeno-associated virus (rAAV) vector comprising an AAVhu68 capsid produced in a production system comprising a nucleotide sequence of SEQ ID NO: 1, or a sequence at least 75% identical thereto which encodes SEQ ID NO:2. The AAVhu68 capsid comprises subpopulations of highly deamidated asparagine residues in asparagine-glycine pairs in the amino acid sequence of SEQ ID NO: 2. Also provided are compositions containing the rAAV and uses thereof. Additionally, rAAV having an engineered AAV capsid comprising at least one subpopulation of vp1 or vp2 proteins having a Val at amino acid position 157 with reference to the AAVhu68 vp1 numbering are provided.

Provided herein are Mycobacterium smegmatis porin nanopores, systems that comprise these nanopores, and methods of using and making these nanopores. Such nanopores may be wild-type MspA porins, mutant MspA porins, wild-type MspA paralog porins, wild-type MspA homolog porins, mutant MspA paralog porins, mutant MspA homolog porins, or single-chain Msp porins. Also provided are bacterial strains capable of inducible Msp porin expression.

The present application relates to the technical field of genetic engineering, in particular to a rice G1 gene mutant g1-1437, its molecular marker and application. The rice G1 gene mutant g1-1437 provided by the present application takes rice G1 gene as reference sequence, the nucleotide sequence of the rice G1 gene is shown as SEQ ID NO. 8; the gene mutant g1-1437 comprises a mutation site that base C at the 112th position is mutated into base T. The mutation causes the chaff homologous transformation of rice into glume shell substances, which can be used as a phenotype screening marker of transgenic rice. The present application further provides a molecular marker identification method of the mutant, which has a good application prospect in the transference of new germplasm.

The present invention provides an anti-cancer vaccine comprising: (i) at least one peptide comprising the amino acid sequence of a neoantigen encoded by a mutant homologous recombination (HR) DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D, wherein the mutant gene comprises a reversion mutation; and / or (ii) at least one polynucleotide encoding the at least one peptide of (i). Also provided are engineered T cells that recognise said neoantigen. Related methods and medical uses of the vaccine and / or engineered T cell are provided, including for the treatment of cancers, such as homologous recombination (HR) deficient cancers that acquire PARP inhibitor resistance or platinum resistance by development of reversion mutations in an HR DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D.

A method for treating a homologous recombination (HR)-deficient cancer, a homologous recombination (HR)-proficient cancer or a cancer that is resistant to DNA repair and DNA damage response (DDR) inhibitor therapy, such as Poly (ADP-Ribose) Polymerase (PARP) inhibitor therapy, is provided, the method comprising administering to a subject an RNA-binding motif protein 39 (RBM39) degrader, such as an aryl sulfonamide. A DDR inhibitor, such as a PARP inhibitor, may also be administered. A composition comprising a RBM39 degrader, such as an aryl sulfonamide, e.g., E7820 or Compound A, and a DDR inhibitor, such as a PARP inhibitor, is also provided.

This invention discloses a method for constructing a multi-target amplicon abundance standard for microorganisms and its application, belonging to the fields of molecular biology detection and microbiome analysis. This standard material screens sequences of common human gut microbiota strains, designs and adds universal primers, and obtains 14 DNA fragments of different lengths through gene synthesis, cloning, and purification, which are then mixed according to a preset abundance. It retains natural characteristics such as primer binding sites and GC content, and can systematically correct technical deviations in amplicon sequencing, solving the problem of species abundance distortion. This standard material functions as both a non-homologous internal reference and a homologous external reference, and can be used for laboratory proficiency testing, reagent kit performance evaluation, and cross-platform data calibration, promoting the leap from relative qualitative to absolute quantitative research in microbiome studies and providing metrological support for the standardization and precision of detection results.

This invention belongs to the field of biotechnology, providing a mouse anti-human ELL2 monoclonal antibody, its preparation method, and its applications. This invention successfully obtained a 2E1 anti-human ELL2 monoclonal antibody and established a hybridoma cell line capable of stably producing this antibody. The binding affinity (KD) of the obtained 2E1 monoclonal antibody to human ELL2 protein reached the picomolar level (approximately 10^-3 kDa). ‑12 The antibody (M) exhibits extremely strong binding ability. Cross-reactivity tests confirmed that it binds only to human ELL2, and shows no binding signal with highly homologous human ELL1, ELL3, and mouse ELL2, thus completely solving the specificity problem of existing technologies.

This disclosure relates to immunogenic compositions comprising attenuated and / or dead streptococcal bacterial strains, including modifications that reduce, decrease, or prevent the functional expression of LytC (or its homologues). Such compositions may be used in vaccine compositions. Immunogenic compositions and / or vaccine compositions may be used in methods for inducing an immune response to at least one target streptococcal species and / or its serotype, and / or for preventing or mitigating infections and / or diseases or conditions in a subject caused by at least one target streptococcal species and / or its serotype.

The application relates to the technical field of genetically modified yeasts, in particular to a Yarrowia lipolytica with high homologous recombination efficiency and / or low lipid degradation capacity and a construction method thereof. The engineered Yarrowia lipolytica comprises a copper ion inducible promoter and a gene related to homologous recombination; the copper ion inducible promoter is selected from any one or more of the following: a pCTR2 promoter, a pMT2 promoter and a pUAS16MT2 constitutive promoter; wherein the gene related to homologous recombination is selected from any one or more of the following: a ylKU70 gene, a ylKU80 gene, a ylRAD51 gene, a ylRAD52 gene, a scRAD52 gene and a scRAD59 gene. The homologous recombination efficiency of the engineered Yarrowia lipolytica is significantly improved. Furthermore, the POX5 gene, the POX2 gene and / or the POX3 gene are knocked out, so that the lipid degradation capacity of the engineered Yarrowia lipolytica is significantly reduced.

The purpose of the present disclosure is to develop a new combination therapy that exerts a superior antitumor effect as compared to administration of an anti-CD26 antibody alone. In order to assess both the function of an immune checkpoint inhibitor and the antitumor effect of an anti-CD26 antibody, it is necessary to be provided with both a binding site on a human CD26 molecule and an immune system of the same lineage of a cancer cell. Thus, in order to acquire data of an immune checkpoint inhibitor and an anti-CD26 antibody, it is essential to perform analysis in a human immune system and a human tumor cell line. The present inventors have made an attempt to produce a human immune system mouse to be used as a model animal for confirming the effect of the combination between ICI and an anti-CD26 antibody, and have successfully produced a model mouse superior for generating human T-cells. Next, the present inventors have studied the effect of combining an immune checkpoint inhibitor and an anti-CD26 antibody in a tumor bearing model by using said mouse. As a result, it was found that an agent using said combination has a synergistic effect that is stronger than when the respective agents are used individually.

The application discloses IV type recombinant collagen protein and a preparation method and application thereof, and relates to the technical field of genetic engineering. The recombinant collagen protein comprises a recombinant collagen single chain; wherein the recombinant collagen single chain is obtained by repeating a collagen monomer fragment as shown in SEQ ID NO. 2 for 2-10 times. The application designs and obtains a recombinant collagen amino acid sequence which can be stably and efficiently expressed in Pichia pastoris and has excellent biological activity by accurately screening and optimizing the functional region sequence of human natural IV type collagen. The sequence is 100% homologous to the corresponding region of human natural IV type collagen, thereby ensuring low immunogenicity of the product and excellent biocompatibility with the human body from the source.

The application discloses a method and system for rapid screening and analysis of homologous genes, and relates to the technical field of biological information and molecular breeding. The method comprises the following steps: obtaining multi-source input files; the multi-source input files comprise a reference genome file, a sample genome file, a reference annotation file and a target gene list file; pre-processing the multi-source input files to obtain pre-processed multi-source input files; the pre-processing comprises standardization processing, integrity detection, format consistency detection, repeated record detection and sequence file information improvement; performing sequence alignment, variation site extraction and variation marking on the pre-processed multi-source input files to obtain gene screening analysis results; and performing visual processing and data management on the gene screening analysis results. The application can reduce manual intervention, improve the efficiency and consistency of data analysis, and realize rapid standardized processing and intuitive result display of genomic variation information.

The present invention relates to combination therapy involving two or more Fc region-containing antigen-binding polypeptides, such as antibodies, wherein the polypeptides have been modified such that hetero-oligomerization between the polypeptides is strongly favored over homo-oligomerization when the polypeptides are bound to their corresponding target antigens. The invention also relates to polypeptides, compositions, kits and devices suitable for use in the combination therapy of the invention.