1843 results about "Homomeric" patented technology

The invention discloses a site for stably expressing protein in a CHO cell gene NW023276806.1 and application of the site, and belongs to the technical field of biological genes. The site belongs to a fixed position in a CHO cell genome, different protein genes are introduced based on a micro-homologous end connection mechanism through a CRISPR / Cas9 tool, and stable expression is carried out. By adopting a site-specific integration method, a target gene is integrated to a stable expression area in a site-specific manner, repeated high-expression monoclonal screening is effectively avoided, and an MMEJ mechanism is introduced to integrate a donor fragment, so that the research and development time for constructing a stable expression cell strain in biological pharmacy can be effectively shortened, and the cost is reduced.

The present invention 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 further relates to a transmembrane pore complex and methods for production of the pore complex and for use in molecular sensing and nucleic acid sequencing applications.

Methods and compositions for modulating a target genome and stable integration of a transgene of interest into the genome of a cell are disclosed. Specifically, provided herein comprises compositions comprising an RNA molecule comprising a reverse complement sequence comprising an exogenous sequence and homology arms, an RNA molecule comprising an endonuclease, and one or more guide RNAs for specific genomic integration of the exogenous sequence.

The invention belongs to the field of molecular biological detection, particularly relates to a quantitative composition, a kit, a method and application, and more particularly relates to a quantitative composition, a kit, a method and application of pathogens. The present invention provides a quantitative composition comprising a homologous vector of segments X1-XN of said pathogen, and a quantitative vector, as well as primers and probes for amplifying both vectors. The homologous vector is creatively introduced, and the concentration of nucleic acid to be detected is artificially increased, so that the stability and accuracy of PCR amplification reaction are improved. Particularly, in a low-load pathogen sample, the pathogen can be well detected.

The present invention relates to ARP2 of plant stigma cells; the invention relates to application of Ca < 2 + > transport capacity damage of homologous genes 1 and 1 in breaking through reproduction isolation of plants. According to the method for breaking through the plant reproductive isolation, a foundation is laid for further research on the relationship of small peptides for regulating and controlling reproductive isolation calcium signals through co-receptors, and a simple and effective target is provided for gene modification for breaking through the reproductive isolation.

The invention belongs to the field of drug design, and particularly discloses a virtual screening method of a small-molecule inhibitor targeting YTHDF1 protein, which comprises the following steps: acquiring a YTHDF1 protein structure, and carrying out homologous modeling to generate various conformation proteins; small molecules combined with the YTHDF1 protein are obtained, bait molecules are generated, and ligand molecules are formed; a ligand molecule is in butt joint with a binding site on the YTHDF1, and the compound is characterized through PLEC fingerprints; the method comprises the following steps: constructing a specificity scoring function by using a machine learning algorithm, carrying out scoring screening on a compound to be screened and a compound butted with YTHDF1 molecules, carrying out affinity prediction, and screening out the small-molecule inhibitor targeting YTHDF1. According to the virtual screening method provided by the invention, the YTHDF1 targeting molecules with high affinity can be accurately screened on a large scale, candidate molecules are provided for research and development of medicines for treating YTHDF1 related diseases, and a foundation is laid for clinical tests and medicine optimization.

The invention relates to the technical field of bioinformatics, in particular to a mining method and system for synthetic biology functional elements and a storage medium. The method comprises the following steps: acquiring functional demand data of a target metabolic pathway; performing evolutionary distance analysis and function prediction on homologous genes of a plurality of species according to the function demand data, and performing protein structural domain conservative classification on preset genome sequence data to obtain candidate element cluster data with function relevance; obtaining expression system data of the host cells; and according to the candidate element cluster data and the expression system data, scoring each functional element based on codon optimization degree, protein folding stability and metabolic load prediction to obtain hierarchical element suitability data. According to the method, factors such as sequence characteristics, expression efficiency and regulation and control network interaction are considered at the same time, multi-level accurate screening is achieved, and therefore the low efficiency and limitation of a traditional screening mode are overcome.

The invention discloses application of a substance with a TaSWEET11f gene knocked out to improvement of gibberellic disease resistance of wheat crops, and relates to the technical field of agricultural biology. According to the application, the correlation between the TaSWEET11f gene and the gibberellic disease resistance is found for the first time, three homologous genes TaSWEET11f-A, TaSWEET11f-B and TaSWEET11f-D of the gene are obtained through screening, the wheat TaSWEET11f gene is specifically knocked out in a receptor material by adopting a CRISPR / Cas9 gene editing technology, gibberellic disease resistance identification is carried out by utilizing a single-flower instillation method, and a result shows that compared with a receptor material Fielder, the wheat TaSWEET11f gene has the advantages that the wheat TaSWEET11f gene can be compared with the receptor material Fielder; the gibberellic disease resistance of a plant edited by the CR-Tasweet11f gene is obviously improved; according to the invention, the wheat TaSWEET11f gene is knocked out by using a CRISPR / Cas9 technology, so that a technical support is expected to be provided for directionally and rapidly creating new germplasm resistant to gibberellic disease, and the method has wide breeding utilization value.

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.

A stable transformant, in which a gene of interest is incorporated into the genome, is simply and efficiently produced.A method for producing a transformant, comprising a step of introducing into a host, linear genome-introduced nucleic acid fragment(s) comprising a gene of interest and a helper plasmid for transformation having a pair of homologous recombination sequences for incorporation of the linear genome-introduced nucleic acid fragment(s), and then selecting a transformant, in which the gene of interest is incorporated into the predetermined position in the host genome and the gene of interest is expressed therein.

According to the invention, a structural domain reaction substrate sequence consisting of Exon1 (E1), P1 and Exon2 (E2) sequences of ribozyme is mutated, and E1, P1 and E2 sequences are mutated under the condition of maintaining the structural stability, so that the Azoarcus group I intron ribozyme still has enzyme activity and can maintain the capability of forming circular RNA (Ribose Nucleic Acid). The invention discloses a flexible vector construction method for preparing circular RNA (Ribonucleic Acid) without limitation of a substrate sequence, which comprises the following steps: determining a target to-be-cyclized site sequence NNUNNNN, and segmenting the target to-be-cyclized site sequence NNUNNNN into E1: NNU and E2: NNNN; with E1 and E2 sequences as references, designing IGS sequences to respectively form complementary pairing with E1 and E2; and 5'and 3 'homologous arms, IRES, CDS and other elements are respectively added. The method provided by the invention can be used for preparing the circular RNA for any target sequence, has no residual sequence, and has relatively high cyclization efficiency. The FlexCirc cyclization system designed on the basis of Azoarcus group I intron ribozyme can form the circular RNA, the cyclization substrate sequence has the characteristic of flexible design, and the cyclization efficiency can realize a relatively high cyclization proportion.

In alternative embodiments, provided are chimeric, synthetic or recombinant antibodies (Ab) against the human homologous box NKX-2. 1 (also known as NK2 homologous box 1, or thyroid transcription factor 1 (TTF-1)) protein, including articles of manufacture and kits comprising them, and methods of making and using them, including, for example, their use in the detection or diagnosis and treatment of cancer. In alternative embodiments, an anti-NKX-2. 1 (TTF-1) antibody provided herein is used with an agent for determining whether NKX-2. 1 (TTF-1) expression or activity is present, reduced or deleted; or the sensitivity of the specific binding of the Ab or the antigen (Ag) binding fragment or protein (ABP) or the monomer or dimer ABP provided by the invention with the squamous cell carcinoma cells is lower than the sensitivity of the specific binding with the adenocarcinoma cells (or binding with lower affinity), so that false positives of the squamous cell carcinoma are less, and the positive recognition of the lung adenocarcinoma is better.

The invention discloses an L-aspartic acid transaminase mutant and application thereof. The L-aspartic acid transaminase mutant is obtained by performing single mutation on the 104th amino acid of the amino acid sequence of L-aspartic acid transaminase. The L-aspartic acid transaminase mutant is used for synthesizing an L-phenylglycine derivative. The L-aspartic acid transaminase mutant is from escherichia coli, homologous sequence analysis and molecular docking simulation are carried out, site-specific mutagenesis verification is combined, and single-point mutation is carried out on the 104 amino acid to obtain the T104S mutant. The L-aspartic acid transaminase mutant disclosed by the invention can be used for efficiently catalyzing to generate an L-phenylglycine derivative, and compared with a wild type, the specific activity of the T104S mutant to o-chlorophenoxyacetic acid is 3.2 times that of the wild type.

The invention belongs to the technical field of biological medicine, and particularly relates to a preparation method of viroid particles displaying scFv antibodies, a product of the viroid particles and application of the viroid particles. The preparation method provided by the invention comprises the following steps: constructing a specific targeting recombinant plasmid, wherein the specific targeting recombinant plasmid is obtained by connecting a vector for expressing virus capsid protein and a coding gene for expressing an scFv antibody display structure through homologous recombination. The vector for expressing the virus capsid protein comprises a coding gene of VSV-G signal peptide, a transmembrane region and an intracellular region, and is as shown in SEQ ID NO. 2. And the coding gene for expressing the scFv antibody display structure is shown as SEQ ID NO. 3-5. According to the preparation method disclosed by the invention, the virus-like particles of which the capsid is a modular component of a specific targeting immune cell are constructed based on a lentivirus system, and 50-90% of infection efficiency can be realized in the immune cell.

The invention belongs to the technical field of biological medicines, and particularly relates to a pleiotropic protein MEL3 and application thereof. The amino acid sequence of the pleiotropic protein MEL3 or the homologous protein of the pleiotropic protein MEL3 provided by the invention has the following general formula: X1GAX2LX3VLX4GLX5ALISWEKRKRX6, x1 is M or L; the X2 is one of V, SI and AI; x3 is one of K, T, KI and KR; x4 is one of KK, TT, SS and VK; x5 is one of P, K, A and T; and X6 is QQ or is free of amino acid. The pleiotropic protein MEL3 or the homologous protein thereof provided by the invention has broad-spectrum antibacterial activity, can achieve anti-inflammatory and antiviral effects at the same time, and provides a new thought for preparing anti-pathogenic microorganism or anti-inflammatory products.

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 discloses methanogen lyase homologous with a PeiR lyase sequence and application of the methanogen lyase, and aims to solve the problem that PeiR lyase protein of a methanogen cell wall peptide bond can participate in a biological process of hydrolyzing archaea cell walls, effectively kill methanogen and reduce methane production, and protein homologous with the PeiR lyase protein has potential methane reduction potential. According to the invention, a series of biological information software is utilized to identify protein sequences coded by methanogens virus from rumen microbiome sequencing data, and sequence homology between the proteins and PeiR protein is further analyzed to obtain a series of methanogens lyases. In order to realize the expression of the lyase, multiple segments of primers are designed to synthesize a target sequence, and the target sequence is successfully expressed in a prokaryotic expression system. Through the detection of crude enzyme liquid, the effectiveness of the lyase in the aspect of reducing the methane yield is verified in an in-vitro gas production test.

Disclosed herein are compounds having the structure of Formula (I): (I) or a pharmaceutically acceptable salt, solvate, hydrate, isomer, tautomer, racemate, or isotope thereof, wherein L1, L2, R1, R2, R3, R4, and m are as defined herein. Pharmaceutical compositions comprising them, processes for preparing them, and uses of them to treat or prevent diseases, disorders, and conditions are also provided. The compounds are modulators of MRGPRX2 or the MRGPRX2 ortholog and are useful in the treatment of diseases, disorders, and conditions related to MRGPRX2 or the MRGPRX2 ortholog activity.

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 invention belongs to the technical field of plant genetic engineering, and relates to medicago sativa polygalacturonase MsPG2, a coding gene thereof and application of the medicago sativa polygalacturonase MsPG2 in plant salt stress resistance, and an amino acid sequence of the polygalacturonase MsPG2 is shown as SEQ ID NO.1 or a derivative sequence or a homologous sequence of the amino acid sequence shown as SEQ ID NO.1. The invention further discloses a preparation method of the medicago sativa polygalacturonase MsPG2. The invention also provides a coding gene of the polygalacturonase MsPG2, wherein the nucleotide sequence of the coding gene is shown as SEQ ID NO. 2; the coding gene can be expressed by salt induction. According to the invention, the cultivation of the MsPG2 transgenic plant is realized by utilizing a genetic engineering technology, the salt tolerance of the plant is obviously improved, an important theoretical basis is provided for the cultivation and breeding work of a new salt-tolerant variety of medicago sativa, and the MsPG2 transgenic plant has a great application value.

The present invention relates to the field of veterinary vaccines, and discloses the development and application of a subunit vaccine for porcine contagious pleuropneumonia. The TbpB-C truncated protein and the AdhE whole protein selected in the antigen protein combination of the vaccine of the present invention are highly homologous in all APP serotypes, and are prepared into subunit vaccines that can provide cross protection to porcine actinobacillus pleuropneumoniae of different serotypes, and the protection rates against APP1 type and APP3 type strains are both 100%. The truncated proteins selected in the antigen protein combination of the present invention are successfully expressed in a soluble form after optimization, and are easy to express and purify in large quantities, thereby reducing production costs. The present invention lays a foundation for the development of an efficient, low-cost, broad-spectrum subunit vaccine for porcine contagious pleuropneumonia, and provides an effective technical means for the prevention and treatment of the disease.

The present invention relates to the pharmaceutical compositions of lectin proteins and its use for the prevention, treatment and cure of inflammation, including inflammatory disease. The invention specifically relates to the pharmaceutical compositions for topical application comprising lectin proteins and its use for prevention, treatment and cure of inflammation due to chemotherapy and / or radiotherapy. The lectin may comprise an amino acid sequence having sequence of SEQ ID NO: 1 or at least 70% homology to SEQ ID NO: 1.

The invention belongs to the technical field of biological information, and particularly relates to a multi-task learning framework for accurate protein secondary structure prediction. According to the method, a highly targeted autoencoder (HTA) is designed as a drive to encode a sequence irrelevant to homologous protein, so that the three-state and eight-state prediction performance of a protein secondary structure is improved. In highly targeted coding features generated by HTA, interference of homologous protein can be reduced, and the feature space utilization rate can be improved. Secondly, under the guidance of biological knowledge, the invention provides a protein secondary structure prediction model (PSSP-MTL) based on a multi-task learning strategy; the PSSP-MTL model can flexibly balance global and multi-scale local features, and full information exchange among multiple tasks is realized based on a multi-gate hybrid expert structure.

The present invention belongs to the technical field of genetic engineering, and particularly relates to the use of an exogenous gene integration site, a homologous recombination vector, and a method for constructing a transgenic pig. The safe site for exogenous gene integration provided by the present invention is the region between the genes LOC100155859 tubulin alpha-1B chain-like and LOC100517052 histone H3.3-like on porcine chromosome 11. The present invention further fully verifies this safe site in transgenic animals and cells. During the passage process, the exogenous gene can be stably and highly expressed, and has no side effects on cells and tissues. Therefore, the safe site provided by the present invention has good application prospects in genetic engineering.