42 results about "Targeted Mutation" patented technology

The invention provides an RNP compound, an electrotransfection composition and a pharmaceutical composition thereof, a CD34 + cell gene editing method using the composition, and a method for obtaining HBG gene target mutation in a CD34 + cell genome.

The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., breast cancer). It relates to mutant PIK3CA-targeted TCRs that specifically target a mutant PIK3CA peptide (e.g., a human mutant PIK3CA peptide), and immunoresponsive cells comprising such TCRs. The presently disclosed mutant PIK3CA peptide-specific TCRs have enhanced immune-activating properties, including anti-tumor activity.

The invention relates to an erythrocyte specific antibody screening test kit expressing a single antigen from a target erythrocyte (RBC) antigen (RhD and RhCE as 2 different antigens derived from RBC and 45 or more antigens in total including some variants of these two antigens) and a preparation method of this test kit. Said antigens are transgenically produced and provide the clearest results compared to traditional methods of antibody screening. Field-targeted mutation process is applied during the preparation of the erythrocyte-specific antibody screening test kit subject to the invention.

The invention discloses an organ-like drug resistance prediction method and device and a storage medium, and relates to the technical field of bioinformatics, and the method comprises the steps: S1, constructing an initial prediction model; s2, acquiring a training data set; s3, training an optimization prediction model; s4, acquiring related data of a to-be-predicted drug; s5, obtaining a prediction result of the drug resistance of the to-be-predicted drug; according to the method, the drug resistance of the organoid to the drug can be predicted more accurately. By fusing multi-dimensional features of gene mutation, target mutation and drug functional groups, the understanding and learning ability of the model to the drug resistance mechanism is enhanced, and the reliability of drug resistance prediction is improved. The method not only can accurately capture key information of influence of gene and target mutation on drug resistance, but also can highlight unique mutant genes of the organoid on drug resistance by comparing feature differences of the organoid and a common cell line, so that an efficient and accurate calculation framework is provided for drug resistance detection.

The present disclosure provides methods and systems for targeting cell with mutations.

This invention provides a testing method, device, and storage medium for stateful network protocols. First, it accurately identifies new state transition events based on the response feedback of the server under test. Then, it extracts corresponding client request message pairs from protocol interaction messages, and further segments them according to field location rules to obtain semantically independent field units. It then identifies differences between field units with the same name to generate candidate field groups, and filters out the candidate field set that truly triggers the state transition through testing. Finally, it performs structure-aware targeted mutations on the test seed based on the candidate field set to generate test cases. By accurately locating the core fields that trigger state transitions, it solves the technical problem of insufficient granularity in trigger condition analysis, making subsequent mutations in the testing process more targeted and effectively improving the accuracy and efficiency of state exploration in fuzzy testing of stateful protocols.

The application provides a primer probe set and a kit for detecting a rifampicin-resistant gene of Mycobacterium tuberculosis, and belongs to the technical field of molecular biology detection.The primer probe set comprises RAA primers and qPCR primers targeting the rpoB gene, probe primers targeting the wild-type rpoB gene, and probe primers targeting the mutant rpoB gene.The application adopts the detection methods of RT-RAA and qPCR in sequence, and the above specific primer probe set can be combined to simultaneously and rapidly detect the 516, 526, 531 and 533 sites of the rpoB gene of Mycobacterium tuberculosis, has good specificity, and the detection sensitivity can reach 5 copies / ul, is 20 times higher than the sensitivity of qPCR (100 copies / ul), and has a 5% detection capability for heterogenic drug resistance mutation; the detection method can also greatly shorten the detection time.

This invention provides a crystal form of compound 1, a salt thereof, and a crystal form of the salt thereof. This invention also relates to pharmaceutical compositions comprising the crystal form of compound 1 and the crystal form of a salt of compound 1. This invention further relates to methods of preparing and using these compositions. Compound 1

The invention belongs to the technical field of biology, and provides a method for detecting low-frequency gene mutation based on PNA-PCR combined with a Cas13a system and application of the method. According to the method, a target mutation sequence is enriched through PNA-mediated allele specific amplification, a Cas13a / crRNA system is used for carrying out high-specificity recognition and fluorescence signal amplification on an amplification product, and the high-frequency gene mutation is detected through the Cas13a / crRNA system. High-sensitivity detection of low-frequency gene mutation in plasma circulating tumor DNA (ctDNA) is achieved, and the lower detection limit can reach 0.1%-0.01% VAF. The invention solves the problems of insufficient sensitivity, complex operation, high cost or strong equipment dependence and the like in the prior art such as next-generation sequencing, digital PCR and the like during low-frequency mutation detection, and is suitable for noninvasive rapid screening and precise diagnosis and treatment of clinical tumor gene mutation.

Provided are a gene mutation detection method and apparatus, a device, a medium, and a product. The method includes acquiring a suspected mutation site of a nucleic acid sample under test, where the suspected mutation site is determined based on first mutation feature data generated by a first mutation detection module upon mutation calling performed on sequencing data of the nucleic acid sample under test, and the recall at which the first mutation detection module identifies gene mutation sites is greater than or equal to a preset recall; acquiring second mutation feature data and third mutation feature data of each suspected mutation site; and inputting the second mutation feature data and the third mutation feature data into a pre-trained target mutation detection model and outputting a mutation detection result of each suspected mutation site.

Provided are a fusion protein useful for performing base editing, a method for performing gene editing in a cell at a target site, a dual guide RNA system, and a guide RNA.SOLUTION: To provide fusion proteins and related molecules useful for performing base editing with reduced or no off-target mutations. The fusion protein can comprise a first fragment comprising a nucleobase deaminase or a catalytic domain thereof, a second fragment comprising a nucleobase deaminase inhibitor, and a protease cleavage site between the first fragment and the second fragment. Also provided are improved prime editing systems comprising prime editing guide RNAs with improved stability.SELECTED DRAWING: None

The invention relates to a genetic variation category prediction method and device based on convex hull geometric constraint, and relates to the fields of bioinformatics, artificial intelligence, applied mathematics and the like, and the method comprises the steps: obtaining multi-modal data corresponding to target genetic variation, including a target variation DNA sequence, a target reference DNA sequence and target semantic text information; performing feature extraction on the multi-modal data through the trained gene variation category prediction model, and predicting the category of target gene variation; wherein loss functions adopted in the model training process comprise a classification loss function used for indicating the difference between a prediction category and a real category, the convex hull geometric constraint loss function is used for indicating the concentration degree of the same type of gene variation corresponding to the distribution range of the feature space and the separation degree of different types of gene variation corresponding to the distribution range of the feature space. According to the invention, based on multi-modal feature fusion and convex hull geometric constraint, efficient and accurate prediction of the gene variation category is realized.

A binding protein, comprising a binding domain having antigen specificity for an antigen peptide: HLA complex, wherein the binding domain comprises a T cell receptor (TCR) α chain variable region and a TCR β chain variable region. The use of the binding protein and a pharmaceutical composition comprising the binding protein in the treatment of cancers associated with the antigen peptide.

This invention relates to a system, kit, and application for the one-pot detection of miRNA and DNA mutations based on CRISPR-Cas12a and aptamers, belonging to the field of biomedical technology. The system for the one-pot detection of miRNA and DNA mutations based on CRISPR-Cas12a and aptamers includes: Cas12a protein, crRNA-R targeting miRNA, aptamer P1, aptamer P2, a linker, AO, and crRNA-D targeting DNA mutations. This invention combines CRISPR / Cas12a with a aptamer-based detection strategy to develop a label-free, direct detection system compatible with smartphones. This system can simultaneously detect EGFR mutations and miRNA-21 expression levels.

The present invention provides a binding protein having antigen specificity for an antigenic peptide / HLA complex, comprising a binding domain containing a T cell receptor (TCR) α chain variable region and a TCR β chain variable region, and uses of the binding protein and pharmaceutical compositions containing the binding protein in the treatment of cancers associated with the antigenic peptide.

The invention belongs to the technical field of gene engineering, and particularly relates to a 3-ketosteroid-delta1-dehydrogenase mutant with improved heat resistance and an application of the 3-ketosteroid-delta1-dehydrogenase mutant. The 3-ketosterone-delta1-dehydrogenase AuKsdD gene derived from arthrobacter urate oxydans is subjected to structural analysis and site-directed mutagenesis design, and a mutant with higher catalytic activity and remarkably enhanced heat resistance compared with a wild type AuKsdD is obtained through directed mutation of key sites E244, K267, T301 and A335. The mutant can keep high catalytic efficiency for a long time under a high-temperature condition, and is suitable for industrial synthesis of steroid drug raw materials.

This invention relates to an intelligent multi-objective optimization method for solving infeasible solutions in complex chemical process industrial applications. This method uses a classification model to screen infeasible solutions and performs targeted mutations to increase the likelihood of transforming infeasible solutions into feasible ones. The method uses classification as a data-driven model to accurately identify specific infeasible solutions and perform targeted mutations. Differentiated mutation operators are used for different types of solutions to ensure that the mutation direction matches the characteristics of the solution. For specific infeasible solutions, uniform mutation is used, constrained by the variable range of Pareto solutions, to correct the solution to the feasible region. This avoids the waste of traditional methods by generating high-quality Pareto solutions early on and avoids local convergence. Validated in dual-tower side-stream extractive distillation and four-tower extractive distillation systems, this method not only significantly improves computational efficiency, reducing optimization time by 35.3% and 20.8% respectively, but also outperforms widely used genetic methods.

The invention relates to the technical field of crossing of bioinformatics, medical genetics and artificial intelligence, and discloses a gene variation pathogenicity automatic rating method and system based on multi-agent game and thinking chain reasoning, and the method comprises the following steps: retrieving data related to a target variation site; based on the related data; the proposal agent, the rejecter agent and the decision maker agent carry out multi-round iteration gene variation pathogenicity rating; and monitoring a rating conclusion output by the decision maker agent and the confidence score in real time, terminating the multi-agent game step when a preset dynamic truncation condition is met, and outputting a final genetic variation pathogenicity rating conclusion. According to the method, model illusion is eliminated through a resistance game, unstructured literatures are analyzed by utilizing a thinking chain, and accurate and transparent rating of gene variation pathogenicity can be realized.

This application relates to a method and apparatus for analyzing the rigidity weaknesses of protein structures based on an atomic node and network constraint model. The method includes: obtaining the first crystal structure of the target protein molecule; performing a free energy minimization simulation on the first crystal structure to obtain an energy-minimized crystal structure; constructing an atomic node and network constraint model of the energy-minimized crystal structure; performing pyrolysis and folding molecular dynamics simulations on the atomic node and network constraint model until the atomic node and network constraint model reaches a state of equilibrium; analyzing the atomic node and network constraint model in equilibrium and obtaining the analysis results; and identifying rigidity weak regions in the target protein molecule based on the analysis results. The scheme provided in this application can calculate the rigidity weaknesses of the protein structure, find more suitable modification sites or regions, and thus enable targeted mutation of the protein to improve the stability of the protein molecule.

The present invention relates, in part, to chimeric proteins comprising mutant interferon-γ and their use as therapeutic agents.

The present invention provides and features novel recombinant T cell receptors (TCRs) that target mutated tumor repression factor TP53. Also provided are cells comprising such TCRs, as well as methods of using the recombinant TCRs and cells expressing the recombinant TCRs to treat cancers associated with mutated TP53.

This invention belongs to the field of biotechnology and relates to a... OsFBX148 Application of genes in regulating plant cold tolerance. This invention reveals a gene in rice called... OsFBX148 Novel functions of the gene and its encoded protein were discovered. Tissue-specific expression analysis showed that the gene was highly expressed in rice roots, and its expression level was significantly upregulated by low-temperature stress. Targeted mutation was performed using gene editing technologies (such as CRISPR / Cas9). OsFBX148 The gene can significantly enhance the cold resistance of rice plants, indicating that the gene plays an important role in regulating the cold resistance of rice. This invention provides an important gene resource for the genetic improvement of cold resistance in rice, and has important application value for breeding crop varieties with enhanced cold resistance and ensuring food security in high-altitude and cold regions.

This invention relates to an evolutionary testing system, method, and apparatus based on LLM (Liquidity Management Model), belonging to the field of computer technology. The evolutionary testing system includes: a multi-dimensional collaborative evaluation module; a targeted breakthrough evolution module configured to generate regular test cases, and when the update of the overall coverage result is deemed stagnant, to locate unreached paths based on the overall coverage result, extract logical constraints, obtain test cases whose execution trajectories are closest to the unreached paths, and infer root causes, thereby generating breakthrough test cases through targeted mutation; and a self-healing closed-loop module configured to execute test cases in the evolved population, capture error information generated during execution and iteratively repair it, storing repaired test cases with a comprehensive fitness exceeding a threshold in a test case library. This solves the problem that existing search methods struggle to penetrate deep code logic and achieve slow coverage improvement in automated testing.

This document provides isolated immune cells that include an exogenous T cell receptor (TCR) having affinity for a splicing factor 3B subunit 1A (SF3B1) peptide as well as methods and materials for making such immune cells. For example, isolated immune cells that included an exogenous TCR having affinity for a mutant SF3B1 peptide, methods and materials for making such immune cells, and methods and materials for using such immune cells to treat mammals (e.g., a human having cancer) are provided.

Soybean plants, plant parts and plant cells capable of producing seeds comprising oil having relatively higher oleic acid levels and lower linoleic and linolenic acid levels than corresponding seeds lacking the targeted mutation.SOLUTION: Disclosed are TALEN compositions and methods of use, including using a multiplexing composition to make targeted mutations in several genes at once, such as the FAD3A / B / C genes, compositions for making targeted mutations in a single gene, such as a gene encoding a FAD2 protein, and combinations thereof. The compositions and methods can provide genetically edited plants, plant parts, and plant cells with improved characteristics as compared to corresponding unmodified plants, plant parts, or plant cells.SELECTED DRAWING: FIG. 1A

The present invention relates to antigen binding proteins comprising a T cell receptor variable region and targeting a KRAS G12V mutant epitope. The present invention also provides fusion proteins, conjugates or compositions comprising the antigen binding proteins, nucleic acid molecules encoding the antigen binding proteins or fusion proteins, vectors comprising the nucleic acid molecules, recombinant cells comprising the nucleic acid molecules or vectors, recombinant cells expressing the antigen binding proteins or fusion proteins, methods of making the antigen binding proteins, fusion proteins or recombinant cells, and therapeutic uses thereof.

This invention discloses a method for detecting nucleic acid mutations with spatial single-cell resolution and its application. The method includes the following steps: (1) pre-staining, fixing, and digesting the tissue sample or cells to be tested; (2) adding isBDA reaction solution for in situ PCR amplification, discarding the reaction solution after the reaction, fixing again, and performing confocal imaging. This invention's detection method is an innovative in situ cell imaging detection method that can achieve localization and visualization at the single-cell level. This invention's detection method selectively inhibits the amplification of wild-type templates, thereby efficiently enriching the target mutation sequence. It can identify cell types while detecting mutation-positive cells, exhibiting high sensitivity and low cost. Furthermore, through specific reaction conditions, it maintains high inhibition efficiency in complex in situ environments, demonstrating good spatial single-cell resolution.

This invention discloses a method for constructing and applying an anti-obesity animal model based on ISCA1 / 2 gene regulation, belonging to the field of biomedical technology. The method utilizes CRISPR-Cas9 gene editing technology to design specific single-stranded guide RNAs targeting the ISCA1 and ISCA2 genes in mice. Cas9 mRNA and sgRNA are introduced into fertilized eggs of C57BL / 6J strain mice via microinjection. The injected embryos are then transferred into pseudopregnant mice to obtain F0 generation chimeric mice. By mating F0 generation mice with wild-type C57BL / 6J mice, F1 generation heterozygous mice carrying the target mutation in the germline are selected, thus obtaining the anti-obesity animal model. This model is not only a phenotypic model but also a mechanistic research model, suitable for drug target validation, energy metabolism pathway exploration, and personalized treatment strategy evaluation.

The present application relates to a gRNA targeting CYP4V2 gene, and a donor nucleic acid molecule comprising a CYP4V2 gene fragment. The present application also relates to use of the gRNA and the donor nucleic acid molecule in the preparation of a medicament for treating Bietti crystalline dystrophy.

The present disclosure provides gRNAs targeting the phospholamban (PLN) gene, expression cassettes, vectors, virions and compositions comprising the same, as well as methods useful for the treatment or prevention of heart disease. In some embodiments, the present disclosure provides expression cassettes and vectors comprising a polynucleotide encoding a Cas endonuclease protein operably linked to a protein expression-driving promoter (e.g., a human troponin T promoter) and / or a polynucleotide encoding a gRNA targeting a sequence of the PLN gene comprising a mutation or deletion operably linked to an RNA expression-driving promoter. The present disclosure also provides guide RNAs, expression cassettes, vectors, virions and compositions for specifically targeting PLN gene comprising a deletion of Arg14.