2525 results about "Homomeric" patented technology

Compounds that are covalent inhibitors of Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2); compositions comprising same; and their use for treating cancers.

The invention belongs to the technical field of bioengineering, and discloses a recombinant yarrowia lipolytica capable of efficiently and rapidly producing sclareol, which is characterized in that optimized sclareol synthase related coding genes ScLPPS, ScSCS, GGPPS1, GGPPS2, ERG20 and tHMGR coding genes are inserted into a yarrowia lipolytica genome; inserting optimized pentadienol utilization pathway coding genes such as IPK, THIM and IDI coding genes; and inserting an optimized ATP: citrate lyase coding gene ACLY to obtain the ATP: citrate lyase coding gene ACLY. The recombinant yarrowia lipolytica is based on knockout of a yarrowia lipolytica strain responsible for coding a non-homologous recombination gene ku70, so that the homologous recombination capability of the yarrowia lipolytica strain is enhanced, gene integration is realized through the homologous recombination function of the yarrowia lipolytica, the genetic stability of the introduced gene can be greatly improved, and the recombinant yarrowia lipolytica strain has a good application prospect. The construction method of the recombinant yarrowia lipolytica strain is efficient and simple to operate.

The present disclosure provides new prime editor guide RNAs for prime editing, constructs for prime editing, and methods for using same. In addition, the present disclosure provides compositions and methods for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and / or targeted mutagenesis (e.g., insertion or deletion). The nucleotide change can include a single-nucleotide change (e.g., any transition or any transversion), an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a prime editor RNA (PEgRNA). The prime editor guide RNA comprises an extension arm that provides a DNA synthesis template sequence which encodes a single strand DNA flap, which is homologous to an endogenous DNA sequence, but which contains the desired one or more nucleotide changes and which, following synthesis by the polymerase (e.g., reverse transcriptase), becomes incorporated into the target DNA molecule.

According to the barley HvPHR1 gene and the application thereof in the aspect of increasing the phosphorus content of barley, rice PHR2 homologous protein serves as bait, homologous comparison means is utilized, it is found that two PHR proteins HvPHR1 and HvPHR2 exist in barley, and it is found that the content of inorganic phosphorus in barley leaves can be remarkably increased through overexpression of the HvPHR1 gene in an HvPHR1 overexpression strain with the normal phosphorus concentration being 200 micrometers NH4H2PO4 and an HvPHR1 overexpression strain with the low phosphorus concentration being 10 micrometers NH4H2PO4 hydroponic culture for three weeks and a wild type control (GP). In conclusion, the function of the HvPHR1 gene in barley low phosphorus stress is defined, and a theoretical basis is provided for cultivation of new phosphorus-efficient barley varieties.

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 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 invention discloses an RNA (Ribonucleic Acid) in-vitro cyclization and rolling circle translation method based on an I-type intron and an application of the RNA in-vitro cyclization and rolling circle translation method. According to the invention, a ribonucleic acid construct is obtained by splitting a specific non-complementary region of the I-type intron, and the preparation of'scarless' (traceless) circular RNA is realized through a ribozyme self-splicing principle and can be popularized to other I-type intron. By optimizing a splitting structure, high-efficiency cyclization can be realized without additionally adding GTP for catalysis under the condition of no homologous arm. Meanwhile, the original part of the ribonucleic acid construct is optimized, so that the cyclization efficiency is further improved. Particularly, a rolling circle translation (RCT) technical platform based on the CITE sequence is established, and the expression quantity of the protein or the polypeptide is greatly improved. Through verification, the cyclization and rolling circle translation method provided by the invention shows potential in vaccine and CAR treatment, and is expected to be used for clinical treatment of various diseases.

The preparation method comprises the following steps: firstly, analyzing the amino acid sequence of an alpha 1 chain of the human XVII type collagen, and selecting partial amino acid fragments which are not easily degraded by endogenous or exogenous protease in non-transmembrane regions of different functional domains of the protein; the recombinant collagen gene fragment (Col17a) n is obtained by repeatedly splicing the recombinant collagen gene fragment (Col17a) n; then introducing homologous promoters from different methylotrophic yeasts to the 5'end of a recombinant collagen gene segment, optimally synthesizing selected (Col17a) n and promoter segments, obtaining a connecting segment by utilizing PCR cloning, connecting the collagen segment (Col17a) n, the promoter segments and a pPIC9K carrier skeleton segment by virtue of a Gibson Assessment seamless connection technology, and obtaining the recombinant collagen gene. And constructing to obtain the pichia pastoris expression plasmid pPIC9K-(Col17a) n of the recombinant human source XVII type collagen.

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.

Provided is a method of characterising a polynucleotide using a transmembrane pore, wherein the pore is a double pore comprising a first Csg G pore, or a homologue thereof, and second CsgG pore, or a homologue thereof.

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 present invention provides antibodies binding to birch pollen allergens, in particular to Bet v 1 allergens, and also binding to Bet v 1 homologous allergens. The present invention also provides compositions and kits comprising distinct antibodies binding to distinct, non-overlapping epitopes of Bet v 1 and Bet v 1 homologous proteins. In addition, the present invention also relates to the use of such antibodies, compositions and kits, e.g. for preventing or treating tree pollen allergies as well as food-related allergies.

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.

The present invention relates to the lectin protein for the treatment and prevention of neurodegenerative diseases. The invention further relates to the recombinant lectin protein is derived from Sclerotium rolfsii lectin having sequence 60% homologous to SEQ ID NO: 4 for the treatment and prevention of Neurodegenerative diseases. The invention specifically relates to lectin protein and its variants is derived from Sclerotium rolfsii lectin having sequence 60% homologous to SEQ ID NO: 4 for the treatment of prevention of Parkinson's disease, Alzheimer's disease, Dementia and symptoms of dementia.

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 present invention relates to polypeptide consisting of three TNF homology domains of TNF-ligand family members proteins (THD) that specifically bind to the extracellular part of TNFR2, wherein C-terminal and N-terminal reference points are defined by consensus sequences. The THIDs are linked by short stretches of further C-terminal and / or N-terminal amino acids of the THD or variants thereof as well as by peptide linkers. These peptides have an improved stability. Furthermore the invention relates to polypeptide multimers comprising several of the polypeptides of the present invention.

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 field of protein rational design and enzyme engineering, and particularly relates to a 7beta hydroxysteroid dehydrogenase mutant and application thereof in preparation of UDCA. Firstly, ruminococcus torquens 7beta-hydroxysteroid dehydrogenase is used as a template, hydrogen bonds are increased through homologous modeling prediction, a mutant 7beta-HSDH-3M is obtained through site-specific mutagenesis, the 50-DEG C thermal stability of the obtained 7beta-hydroxysteroid dehydrogenase is remarkably improved, the 7beta-hydroxysteroid dehydrogenase is used for catalyzing 80g / L L7-KLCA to generate UDCA, the conversion rate exceeds 99%, and the 7beta-hydroxysteroid dehydrogenase can be used for preparing a mutant 7beta-HSDH-3M mutant 7beta-HSDH-3M mutant 7beta-HSDH-3M mutant 7beta-HSDH-3M mutant 7beta-HSDH-3M. Complete conversion (greater than 99%) of a product substrate is realized through high conversion rate of 7beta-HSDH.

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 present invention provides antibodies binding to birch pollen allergens, in particular to Bet v 1 allergens, and also binding to Bet v 1 homologous allergens. The present invention also provides compositions and kits comprising distinct antibodies binding to distinct, non-overlapping epitopes of Bet v 1 and Bet v 1 homologous proteins. In addition, the present invention also relates to the use of such antibodies, compositions and kits, e.g. for preventing or treating tree pollen allergies as well as food-related allergies.

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.