1072 results about "Homomeric" patented technology

Disclosed herein are certain thiadiazolyl derivatives Formula (I):that inhibit DNA Polymerase Theta (Polθ) activity, in particular inhibit Polθ activity by inhibiting ATP dependent helicase domain activity of Polθ. Also, disclosed are pharmaceutical compositions comprising such compounds and methods of treating and / or preventing diseases treatable by inhibition of Polθ such as cancer, including homologous recombination (HR) deficient cancers.

The invention discloses a construction method and application of an NMD escape model of an Alport syndrome mouse. A non-human animal model carrying Col4a5 gene c.4432delG frame shift mutation is prepared on the basis of a CRISPR / Cas9 gene editing technology. The method comprises the following steps: co-injecting gRNA of a 49 exon of a targeted Col4a5 gene, homologous recombinant donor oligonucleotide containing c.4432delG mutation and Cas9 nuclease into a mouse fertilized egg, and carrying out embryo transplantation to obtain an F0-generation mutant mouse; a mutation site is verified by combining PCR (Polymerase Chain Reaction) with sequencing, and a stably inherited mutation line is established through two generations of breeding. Through verification, the model accords with pathological characteristics of the Alport syndrome, can stably simulate typical clinical manifestation and pathological characteristics of the human X-linked Alport syndrome, and can be used as an important tool for research of the Alport syndrome.

The invention relates to the technical field of biomedicine, discloses mutant photo-induced ion channel ChR-2 protein, and further discloses a nucleic acid construct, an expression vector, a cell, related application and a computer model. The light-sensitive channel ChR2 protein mutant obtained by the invention has stronger light current, and the light-sensitive capability of the light-sensitive channel ChR2 protein mutant is at least improved by 100 times; besides, the invention also obtains a nucleotide sequence for coding the light-sensitive channel ChR2 protein mutant, constructs a recombinant expression vector, and obtains the light-sensitive channel ChR2 protein with higher expression quantity and stronger light sensitivity, and the light-sensitive channel ChR2 protein is very suitable for expression in cells of mammals (especially human); according to the invention, the rhodopsin in different channels is systematically studied by modifying the position G224 in the helix 6 of seven transmembrane helix motifs, which proves that the mutation of the position G224 in the helix 6 in WT ChR2 accelerates the photosensitivity of the channels, and the considered position is homologous in the helix 6 of the rhodopsin in different channels.

The invention belongs to the technical field of biological agriculture, and particularly relates to application of a receptor-like kinase gene MdSRF3 and an encoding protein thereof in regulation and control of apple disease resistance. The receptor-like kinase gene MdSRF3 for negative regulation and control of rot resistance is identified from apples, the CDS sequence of the receptor-like kinase gene MdSRF3 is as shown in SEQ ID NO: 1, and the amino acid sequence of coded protein is as shown in SEQ ID NO: 2. Researches show that over-expression of the gene significantly weakens apple disease resistance, and down-regulates expression of defense-related genes; the silence of the gene enhances the disease resistance of the apple. Different from the positive regulation and control functions of homologous proteins in arabidopsis thaliana, potatoes and rice, the negative regulation and control characteristics of the receptor-like kinase gene MdSRF3 provide a new perspective for research of a plant disease-resistant mechanism, provide a new gene resource for apple disease-resistant breeding, and have significant application values and industrialization prospects.

The invention belongs to the technical field of biotechnology and animal models, and discloses a double-person-derived mouse model for simulating a tumor immune microenvironment and a construction method and application thereof. The method comprises the following steps: firstly, pretreating NSG immunodeficient mice by adopting low-dose whole-body irradiation in combination with double-antibody targeted bone marrow depletion, and transplanting CD34 + hematopoietic stem cells from the same human donor to complete human immune system reconstruction; separating tumor primary cells, tumor-related fibroblasts and tumor vascular endothelial cells of the same donor, performing three-dimensional co-culture to obtain homologous human tumor organs, and performing in-situ inoculation to immune reconstruction mice to obtain a target model. The core defects of MHC mismatching, low immune reconstruction efficiency, poor tumor immune microenvironment simulation degree, low clinical consistency and the like of an existing model are overcome, and the method can be used for tumor immune treatment drug screening, microenvironment mechanism research and personalized tumor treatment scheme verification.

The present invention relates to modified Dda helicases which can be used to control the movement of analytes such as polynucleotides. The modified Dda helicases are used in analyte detection and characterisation. The present invention also relates to novel protein pores and their uses in analyte detection and characterisation. The invention particularly relates to an isolated pore complex formed by a CsgG-like pore and a modified CsgF peptide, or a homologue or mutant thereof, thereby incorporating an additional channel constriction or reader head in the nanopore.

The invention provides an application of WNT7B in construction of a myopia animal model. Homologous genes wnt7ba and wnt7bb of the WNT7B in the zebra fish are knocked out or knocked down by applying a CRISPR / Cas9 gene editing technology, an animal model of which the eye axis length is remarkably increased, the eyeball movement frequency is remarkably reduced and the light response is reduced is obtained, and the result shows that the WNT7B is related to the high myopia. The model provides a favorable tool for pathogenesis and drug screening of high myopia, and has a good application prospect.

The invention relates to the field of agricultural products, and particularly discloses a polypeptide for improving plant disease resistance, and the polypeptide is LAND2 small peptide and homologous peptide thereof. The LAND2 small peptide disclosed by the invention is screened and found from an arabidopsis thaliana proteome, and homologous peptides of the LAND2 small peptide are respectively derived from chilies and cucumbers. Tests prove that when the LAND2 small peptide is externally applied to arabidopsis thaliana, the local and systematic resistance of plants to botrytis cinerea can be enhanced, and the LAND2 small peptide has broad-spectrum immunocompetence in chilies and cucumbers. The polypeptide is practically applied to agricultural production, can enhance the disease resistance of plants and improve the yield and quality of the plants, and has practical popularization and application values.

The application discloses a kind of carrier, kit and application for long-acting gene knockdown of animal parasitic nematode, belong to the field of animal parasitic disease prevention and control.The lentivirus vector in the application integrates specific coding sequence to the genome of the infected nematode, stably and continuously expresses short hairpin RNA (shRNA) in the nematode, efficiently produces primary single-stranded small RNA (siRNA), these siRNAs target homologous target gene mRNA to cause its degradation, realize stable and continuous gene silencing effect.The application breaks through the bottleneck of traditional animal parasitic nematode RNA interference (RNAi) technology with low efficiency and instability, significantly improves the timeliness of conventional RNAi, can be used to establish long-acting RNAi technology system of animal parasitic nematode, has application value in the research of host in vivo process such as nematode infection, parasitism and pathogenicity and animal parasitic nematode disease prevention and control.

The invention belongs to the field of antibody development, and discloses a screening method and application of a human-mouse protein high homologous target antibody based on a fully humanized antibody mouse. Aiming at the problem of weak antibody response caused by immune tolerance of human-mouse high homologous targets (protein homology is greater than or equal to 95%), the following scheme is provided: in embryonic stem cells (ES cells) of HUGO-Mabfully humanized antibody transgenic mice, a mouse target gene (such as ACVR2A) is knocked out through a Turbo Knockout technology, and homozygous knockout ES clones are screened; carrying out microinjection on the clones to the whitened B6 mouse blastocyst, and transplanting a pregnant mouse to obtain a Founder mouse; the Founder mouse is subjected to target antigen immunization for more than or equal to 4 times (the Freund's complete adjuvant is used for the first time), and the titer of the serum antibody is detected. According to the invention, 100% homozygous knockout chimeric efficiency is realized in the Founder stage, the mouse construction period is shortened from traditional 8-10 months to 3-4 months, and the diversity and affinity of the antibody are significantly improved (titer reaches 1: 729,000). The obtained antibody can be used for preparing medicines for treating tumors or autoimmune diseases.

The disclosure features systems and methods for correcting a mutation in the human beta-globin (HBB) gene in a cell or population of cells. The disclosure also features methods of increasing repair of a DNA double stranded break (DSB) in an HBB gene by the homology-directed repair (HDR) pathway. The disclosure also features compositions for use in the methods.

The present disclosure relates to antibodies and antibody conjugates that selectively bind to TROP2 and its isoforms and homologs, and compositions comprising the antibodies and antibody conjugates. Also provided are methods of using the antibodies and compositions, such as therapeutic and diagnostic methods.

The present disclosure provides, among other things, methods for treating cancer comprising administering an effective dose of azenosertib, or a pharmaceutically acceptable salt thereof, to subjects selected to have a homologous recombination repair deficiency (HRD).

The disclosure relates to methods for redirecting an active form of an endogenous cytokine to a target cell or target tissue of interest in a biological system or subject in need thereof by administering a multi-specific binding molecule comprising (a) a binding domain that specifically binds to an active form of a cytokine and (b) a binding domain that specifically binds to an epitope on a molecule that is a marker on a target cell or tissue, wherein the multi-specific binding molecule, when bound to the cytokine, does not block or only partially blocks, the ability of the cytokine to bind to and agonize a cognate receptor for the cytokine.

The invention relates to the technical field of drug target prediction, and discloses a drug target intelligent prediction method and system, and the method comprises the following steps: 1, obtaining the structure data and sequence data of a target protein, and the homologous sequence data of the target protein; 2, performing molecular dynamics simulation according to the structural data, and calculating to obtain a dynamic conformation feature vector; according to the sequence data, an evolutionary information feature vector is obtained through calculation; analyzing the structural data to obtain an interaction feature vector; 3, obtaining an enhanced dynamic conformation feature vector, an enhanced evolutionary information feature vector and an enhanced interaction feature vector through an attention fusion mechanism, respectively obtaining importance weights through a gating fusion mechanism, and obtaining a fusion feature vector by adopting element-by-element multiplication and combining the importance weights; and 4, inputting the fusion feature vector into a graph neural network prediction model to obtain a target druggability probability.

The disclosure relates to methods for redirecting an active form of an endogenous cytokine to a target cell or target tissue of interest in a biological system or subject in need thereof by administering a multi-specific binding molecule comprising (a) a binding domain that specifically binds to an active form of a cytokine and (b) a binding domain that specifically binds to an epitope on a molecule that is a marker on a target cell or tissue, wherein the multi-specific binding molecule, when bound to the cytokine, does not block or only partially blocks, the ability of the cytokine to bind to and agonize a cognate receptor for the cytokine.

The invention belongs to the technical field of biological medicine, and provides CKS1B serving as an immunotherapy response prediction biomarker and application of the CKS1B, and according to the application, CKS1B serves as an immunotherapy response marker, and a CKS1B inhibitor is combined with an active component to treat a model mouse. In-vitro cell experiments are adopted to evaluate the immunotherapy prediction effect of the CKS1B as a biomarker on esophageal squamous carcinoma, a Cks1b overexpression tumor mouse model, a homologous mouse model and a human immune reconstruction mouse model are established, and a CKS1B inhibitor is combined with active ingredients to treat the two models; results show that the CKS1B inhibitor combined with the active component can promote removal of esophageal squamous carcinoma cells by CD8 + T cells, inhibit interferon signal channels and antigen presentation, effectively recover immune response, inhibit tumor cell proliferation and significantly reduce tumor volume, so as to achieve the purpose of treating esophageal squamous carcinoma.

The invention relates to tumor-targeted trimeric polypeptides based on the homotrimerization region from collagen XV or XVIII and which contain domains capable of specifically binding to and activating receptors of the TNFR family of costimulatory receptors as well as to the uses thereof in the treatment of cancer.

The invention discloses a cross-graph modeling three-dimensional RNA inverse folding method based on multi-structure comparison, and the method comprises the steps: carrying out the multi-structure comparison of a target RNA structure and an RNA structure database at an offline stage, obtaining a closest similar structure, carrying out the alignment processing, extracting node and edge features from the target RNA structure, and generating a training set through cross-structure coding; the training module is used for training a sequence decoder; in the online stage, through a trained sequence decoder, real-time input and cross-structure coded features are decoded, and after sequence probability distribution is obtained, a design sequence is obtained through temperature coefficient sampling. According to the method, the multi-structure comparison technology and the graph neural network are combined, and the accuracy and diversity of RNA sequence design are remarkably improved by utilizing the evolutionary conservative property of the target RNA structure and the homologous structure of the target RNA structure.

The present disclosure relates to enzymes, compositions and methods for performing conditional homologous recombination of a targeted DNA molecule or genome by using modified proteins comprising nucleic acid DNA binding proteins with protease-conditional recombinase (hereinafter “ProRec”) activity. Namely a new cre recombinase pro enzyme, compositions / kit and sensors comprising the cre recombinase pro enzyme of the present disclosure. Namely, a cre recombinase pro-enzyme, for identifying and quantifying proteolytic activity in a disease or an infection, comprising intein mediated circularization, a flip-excision cassette comprising an output reporter and / or effector protein; a linker sequence cleavable by a protease.

The invention relates to the technical field of biological medicines, in particular to a CKAP4-targeted tumor antigen peptide, a vaccine and application of the CKAP4-targeted tumor antigen peptide. The invention provides a high-immunogenicity tumor antigen peptide RLTELTKSI targeting human and mouse homologous CKAP4 protein, and the tumor antigen peptide and a vaccine thereof can realize efficient killing of CKAP4 positive tumor cells and remarkable inhibition of CT26 subcutaneous tumor by activating specific CD8 + T cell immune response. The traditional single-target limitation is broken through, the co-expression characteristic of CKAP4 in tumor cells and immunosuppressive cells (TAM / TAN) is utilized, a double-target and double-channel mechanism is initiated, and the immunosuppressive state of cold tumors is effectively reversed by inducing T cells to synchronously kill tumor cells and remodel an immune microenvironment. According to the technology, CKAP4 is expanded from an antibody target to a T cell vaccine target, lasting specific CTL response can be stimulated, the off-target risk of antibody treatment is avoided, a universal treatment scheme can be provided for solid tumors, and the clinical transformation potential and the treatment broad spectrum are remarkably improved.

The invention belongs to the technical field of microbial engineering, and discloses a method for producing eicosapentaenoic acid (EPA) with high yield by schizochytrium limacinum based on random mutation and low-temperature screening and application, and the method comprises the following steps: driving overexpression of a G418 resistance gene through a P2520 promoter, constructing a random insertion mutant library, and screening to obtain a schizochytrium limacinum mutant strain with a randomly mutated genome; coating in a culture medium containing G418 resistance for culturing, and screening out strains which are resistant to low temperature and good in growth state at 15 DEG C; and inoculating into a fermentation culture medium, adding MgSO4 with the final mass concentration of 0.1% at the initial stage of fermentation, supplementing MnCl2 with the final mass concentration of 0.05% when fermentation is performed for 72 hours, and culturing to obtain a mutant strain. According to the invention, the G418 resistance gene carried by the plasmid is randomly inserted into the schizochytrium limacinum genome, and low-temperature induced screening is combined, so that the target limitation of traditional homologous recombination is broken through, and a stable strain with multiple mutation superposition can be obtained through enrichment.

The invention discloses a fusion protein taking peptide-N-glycosidase as an active component as well as a preparation method and application of the fusion protein, and belongs to the technical field of biological medicines. The fusion protein comprises: (a) peptide-N-glycosidase or a catalytically active fragment thereof; (b) an immunoglobulin Fc domain, or a combination of a tumor or immune cell antigen binding domain and an immunoglobulin Fc domain; (c) a linker peptide; wherein the form of the tumor or immune cell antigen binding domain is Fab, scFv or VHH; the peptide-N-glycosidase or the catalytic activity fragment of the peptide-N-glycosidase is connected with the Fc structural domain of the immunoglobulin through the connecting peptide; the immunoglobulin Fc domain mediates the fusion protein to form a homodimer or a heterodimer. According to the invention, the synergistic function of targeted binding and local deglycosylation of the target molecule is realized, so that the immunosuppressive activity of the target molecule is interfered, and the anti-tumor immune response is enhanced.

The invention relates to a preparation method and application of a medicine-food homologous compound with weight-losing and lipid-lowering effects. According to the present invention, the weight of the obese mouse can be reduced by 23.23% at most, the serum total cholesterol is reduced, the leptin secretion is reduced, AST (aspartate transaminase) and ALT (alanine transaminase) have no significant difference compared to the model mouse, the volume of epididymal fat and inguinal fat cells is reduced, the number of cells in unit area is significantly increased, the fatty liver sample is relieved, the TMEM26 gene expression in the epididymal fat is significantly increased, and the weight of the obese mouse can be significantly reduced; the expression quantity of the UCP1 gene in brown fat is obviously increased. The traditional Chinese medicine composition adopts medicinal and edible substances as raw materials, is widely applicable to people, is more suitable for prevention and treatment of chronic diseases, is safe and effective, and causes little damage to liver and kidney after long-term use.

The invention belongs to the field of large protein complex structure prediction, and discloses a large protein complex structure prediction method integrating docking and assembly algorithms, and the method comprises the steps: predicting the monomer structure of each chain and the structure of each sub-component based on the sequence information of a target complex; judging whether the compound is a homologous compound or not according to input sequence information, and applying symmetric docking, asymmetric docking and assembling methods to the homologous compound; asymmetrical docking and assembling methods are applied to heterologous compounds according to chain number self-adaption distinguishing; and performing structure prediction on the target compound based on the selected modeling strategy, then performing unified sorting on results of different modeling methods, and finally outputting a group of prediction results with the optimal sorting as a representative structure of the target compound. According to the method, the modeling precision can be improved while the conformational diversity is ensured, the prediction capability on the large protein compound structure is expected to be remarkably enhanced, and the urgent demand on high-precision compound structure information at present is met.

This vector for nucleic acid introduction contains a nucleotide sequence that encodes a Cas protein, a nucleotide sequence that encodes a guide RNA, and a nucleotide sequence of a nucleic acid to be introduced. The guide RNA targets an intron adjacent to the 5' side, with reference to a sense strand, of an exon that includes a stop codon. Also provided is a nucleic acid introduction method comprising a step for introducing a nucleic acid to be introduced through non-homologous end joining by targeting an intron that is adjacent to the 5' side, with reference to a sense strand, of an exon that includes a stop codon.

The invention provides a lipid nanoparticle for the targeted combined delivery of a CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR-Cas9) system and a single-stranded DNA (deoxyribonucleic acid) repair template of the liver, and the lipid nanoparticle is prepared from an ionizable lipid ALC-0315, a PC (polycarbonate) lipid DOPC (dioctyl-phthalate), cholesterol and DMG-PEG (dimethyl glycol-polyethylene glycol) (2000) according to a molar ratio of 50: 10: 38.5: 1.5. The lipid nanoparticles can simultaneously package Cas9 mRNA (messenger ribonucleic acid), sgRNA (small guide ribonucleic acid) and a single-stranded DNA (deoxyribonucleic acid) repair template required by homologous directional repair (HDR) gene editing according to a certain proportion to prepare All-in-one LNP. According to the All-in-one LNP, the three nucleic acids are successfully delivered in a liver-targeted combined manner, HDR editing is successfully performed on the liver of a young rat, and an accurate and efficient tool is provided for in-vivo editing.

The invention discloses a pCDNA-3xHA-hTERT-IRES2-mCherry fusion expression vector as well as a construction method and application of the pCDNA-3xHA-hTERT-IRES2-mCherry fusion expression vector. The construction method comprises the following steps: mixing an mCherry gene segment and an IRES2 gene segment which are respectively obtained by PCR (Polymerase Chain Reaction) amplification in equal mass, then carrying out fusion amplification to obtain an IRES2-mCherry fusion gene segment, and carrying out homologous recombination on the IRES2-mCherry fusion segment and a pCDNA-3xHA-hTERT linearization vector. On the basis of a pCDNA-3xHA-hTERT stent vector, a pCDNA-3xHA-hTERT-IRES2-mCherry fusion expression vector with red fluorescence is successfully constructed, and the fusion expression vector can be used as a fusion expression vector of the pCDNA-3xHA-hTERT-IRES2. The construction method is simple and efficient, enzyme digestion is not needed, and the constructed pCDNA-3xHA-hTERT-IRES2-mCherry fusion expression vector can be subsequently used for transfecting bovine endometrial epithelial cells, so that the immortalized bovine endometrial epithelial cells are obtained.

The invention relates to the technical field of synthetic biology, in particular to a squalene high-yield saccharomyces cerevisiae engineering bacterium and a construction method and application thereof.Saccharomyces cerevisiae CEN.PK.2-1D is used as an original strain, pentose phosphate pathway genes ZWF1, GND1, TAL1 and TKL1 and IDP1 genes of TCA circulation are integrated in a genome of the original strain through homologous recombination, and the squalene high-yield saccharomyces cerevisiae engineering bacterium is obtained. Constructing a dual-channel cofactor supply system to improve the intracellular NADPH level and the NADPH / NADP + ratio; according to the saccharomyces cerevisiae genetic engineering strain Sc-Sq04 constructed by the method disclosed by the invention, the yield of squalene obtained by shake flask fermentation reaches 741.08 + / -28.9 mg / L by further integrating all genes of an MVA way, ERG20 and ERG9 genes, and a new thought is provided for transforming saccharomyces cerevisiae to synthesize terpene compounds and promoting industrial application.

The invention discloses a liver protection composition containing glutathione-rich yeast. The liver protection composition is prepared from the glutathione-rich yeast, turmeric, silybum marianum, enzymolysis polypeptide with homology of medicine and food and anti-inflammatory and anti-oxidation auxiliary components. Wherein the medicine and food homologous enzymolysis polypeptide is prepared from radix puerariae through neutral protease-cellulase double enzymolysis, the polypeptide sequence is identified as Leuu-Val-Glu-Pro-Ala, and the medicine and food homologous enzymolysis polypeptide has the capacity of remarkably inhibiting LPS-induced RAW264.7 cell NO release and removing DPPH free radicals. According to the composition, through multi-component synergism, in an anti-alcohol experiment, the blood alcohol concentration decline rate of a mouse can be remarkably increased, the MDA content of liver tissue is remarkably reduced, and no acute toxic reaction exists. The composition has the functions of protecting the liver and dispelling the effects of alcohol, is safe and effective, and is suitable for the field of health-care products or functional foods.