46 results about "Specific mutation" patented technology

The present invention provides a computer-implemented method for predicting the treatment response of a subject having a lung cancer to an immune checkpoint inhibitor (CPI) therapy, the method comprising: providing a mutation profile of the subject, said profile comprising the presence or absence of cancer-specific mutations at one or more locations in at least five genes selected from the group consisting of: NF1, STK11, TSC2, BRCA2, BRAF, STAG2, U2AF1, BRIP1, PDGFRA, CTNNA1, PDK1, FGF10, and FLT1; analysing the mutation profile to classify the profile as matching the mutation profile of a response signature or a resistance signature, wherein the subject is predicted to be likely to respond to the CPI therapy if the mutation profile for the subject is classified as matching the mutation profile of the response signature and is predicted to be likely not to respond to the CPI therapy if the mutation profile for the subject is classified as matching the mutation profile of the resistance signature. Also provided are related methods and systems for predicting the treatment response of a subject having a lung cancer to an immune checkpoint inhibitor (CPI) therapy.

A new technique for improving the secretion production of a heterologous protein by a coryneform bacterium is developed, and thus a method for the secretion production of a heterologous protein is provided. A coryneform bacterium having a secretion production ability of a heterologous protein and modified to maintain a phoS gene having a specific mutation is cultured to produce a heterologous protein by secretion.

Genetically modified zebrafish, in which mutation combinations frequently identified in human AML are stably expressed in the stem cell population of the fish, are provided. The combination of mutations result in morphologic, cytochemical and molecular changes of its blood cells that are remarkably similar to those in human AML. The zebrafish model provides a foundation for the study of AML initiation and progression and a high throughput in vivo drug screening platform to identify personalized therapies for AML based on specific mutation combinations. The method of drug screening includes contacting embryos or adult fish containing mutations as disclosed herein, with a test agent, at test concentrations and test intervals to determine the therapeutic effect if any, of the test agent.

This disclosure relates to a technique for identifying tumor-specific mutations through integrated analysis of next-generation sequencing data using machine learning models. In certain embodiments, a computer implementation method is provided, comprising: generating sequence reads from one or more samples collected from the same patient; generating variant calling files by analyzing the sequence reads corresponding to each of the one or more samples; generating a list of candidate somatic variants by comparing the variant calling files; generating a score for each of the candidate somatic variants in the list of candidate somatic variants using a classification machine learning model, wherein the score is generated based on a plurality of classifications generated by the classification machine learning model; determining the ctDNA status for the patient based on the score, wherein the ctDNA status is either positive or negative; and generating a report providing the ctDNA status for the patient.

This invention discloses a sequencing technique for enriching mutations after library construction. The co-priming amplification (Co-PCR) technique of this invention couples a mutation probe to a short P5 / P7 primer. This short primer has a low melting temperature (Tm) and cannot hybridize and amplify on its own at the reaction temperature. Only when the mutation probe hybridizes to the mutation site can it assist the coupled short P5 / P7 primer in hybridizing to the adjacent P5 / P7 sequence at the end of the pre-library, initiating amplification. Therefore, this Co-PCR technique not only amplifies a specific mutation in a specified gene but also amplifies from both ends of the original pre-library, replicating the complete sequence information of the pre-library, including sequencing adapters, indexes, and sequencing primers. The amplified products can be directly sequenced after purification. By optimizing the co-primers, Co-PCR enrichment amplification of five sites in the pre-library was achieved, resulting in nearly 100-fold enrichment.

The invention discloses a construction method and application of a basic group editor of industrial bacteria of cephalosporium acremonium based on CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9), and belongs to the field of gene engineering. The cephalosporium acremonium industrial bacterium base editor provided by the invention can be used for specific mutation of a specific site of the DNA level of the cephalosporium acremonium industrial bacterium. The cytosine base editor CBE constructed by the invention is a plasmid comprising a fusion protein A and an sgRNA expression element. The base editor CBE can successfully mediate C.G-T.A, is suitable for the base editor of the high-yield CPC cephalosporium acremonium industrial bacteria, utilizes the protoplast, is high in conversion efficiency, can mediate specific site mutation in the cephalosporium acremonium industrial bacteria, and has application value.

A method of treating a subject having been diagnosed as having cancer with an immunotherapy is described. The method comprises targeting one or more clonal neoantigens selected using a method comprising determining whether a tumour-specific mutation is likely to be clonal in a subject. The method comprises providing sequence data from one or more samples from the subject comprising tumour genetic material, the sequence data comprising for each of the one or more samples, and determining the likelihood that the tumour-specific mutation is clonal as a posterior probability depending on: a prior probability of the mutation being clonal, and the probabilities of observing the sequence data if the tumour-specific mutation is (i) clonal and (ii) non-clonal, in view of a tumour fraction for each of the one or more samples and one or more candidate joint genotypes.

The present technology relates to methods, computing devices, and systems for predicting the fitness of mutant p53 based on the loss of transcription factor function and immunogenicity of a particular TP53 mutation. The fitness of mutant p53 may be used to determine whether a patient will benefit from a particular anti-cancer therapy such as immune checkpoint inhibitor therapy, adoptive T-cell therapy, or prophylactic cancer vaccine therapy.

This invention discloses the application of the VDAC2 gene or VDAC2 protein as a target in screening drugs for the treatment of retinitis pigmentosa, relating to the field of biomedical technology. The drug is one that reduces the expression level of the VDAC2 gene or inhibits the expression level or activity of the VDAC2 protein; the CDS sequence of the VDAC2 gene is shown in SEQ ID NO.1. This invention uses a rod cell-specific promoter to inhibit VDAC2 expression, which can significantly improve the survival rate of local photoreceptor cells. This method intervenes in the early stages of the disease, conforming to the natural course of RP. It strengthens the function of rod cells before a large number of photoreceptor cells die, delaying their degenerative process and indirectly protecting cone cells, thereby prolonging the patient's effective visual retention time. This overcomes the shortcomings of existing gene therapies, which are mainly applicable to late-stage or specific mutation types, and provides a therapeutic basis for retinitis pigmentosa.

The invention belongs to the technical field of agricultural biology, and particularly discloses a grape germplasm innovation method based on X-ray gradient mutagenesis and an LD50 precise prediction model, and the method comprises the following steps: selecting an annual grape branch for vernalization treatment, and trimming the annual grape branch into a single-bud stem segment; setting an irradiation time gradient, accurately calculating an LD50 value through a cubic spline interpolation model, and carrying out X-ray irradiation on the single-bud stem segment according to the LD50 value; after irradiation, performing cutting and liquid paraffin sealing, and then performing cuttage, potting and field planting treatment; performing secondary vernalization on mutagenesis plant branches, trimming the mutagenesis plant branches into single-bud stem segments, collecting tender leaves after cutting survival, extracting genome DNA, performing whole genome sequencing, and accurately distinguishing mutagenesis specific variation and natural variation. By establishing a complete technical system of standardized vernalization, gradient irradiation, LD50 accurate calculation and whole genome verification, the problems of inaccurate irradiation parameters, nonstandard material treatment, low mutation screening accuracy and the like in the prior art are solved.

The application provides a pyroglutamic acid transaminase mutant and application thereof, the mutant is obtained by mutation on the basis of wild-type pyroglutamic acid transaminase, and specific mutation includes at least one of the following sites: (1) the 13th isoleucine is mutated into arginine; (2) the 35th valine is mutated into arginine; (3) the 183rd asparagine is mutated into aspartic acid; and the mutant is suitable for industrial enzymatic production of L-aspartic acid and the process of amino acids taking L-aspartic acid as a precursor; especially, the I13R / V35R / N183D mutant obtained by modification has high positive catalytic activity and strict direction selectivity, and completely loses the reverse reaction activity of decomposing L-aspartic acid; the mutant is overexpressed with phosphoenolpyruvate carboxylase in L-threonine production strain THRS-6, and a high-efficiency L-threonine synthesis metabolic pathway is constructed, and the yield of L-threonine is significantly improved when glucose is used as a substrate.

The application discloses a kind of identification Pinb The primer sequence for amplifying the dCAPS molecular marker is shown in SEQ ID No.10-SEQ ID No.11.The application uses a strong wheat variety as a transgenic receptor, edits the variety by gene editing Pinb Gene to make it produce specific mutations and lose function, and creates a new wheat germplasm with greatly improved grain hardness and improved flour quality. Pinb The effect is stronger than that of reported single knockout of the gene, and the resistance to wheat scab does not decrease after knockout, and the content of DON toxin in flour is actually reduced.

The invention provides a primer and probe combination, a kit and a method for quantitatively detecting the JAK2V617F gene mutation rate, and the primer and probe combination comprises a primer and probe set targeting JAK2V617F mutation sites and a primer and probe set of reference genes GPI, according to the primer probe set targeting JAK2V617F mutation sites, the nucleotide sequence of an upstream primer of a specific mutation site is any one of SEQ ID NO.1-7, the nucleotide sequence of an upstream primer of a specific wild type site is any one of SEQ ID NO.9-14, the nucleotide sequence of a universal downstream primer is SEQ ID NO.8, and the nucleotide sequence of a probe is SEQ ID NO.15. The invention further discloses a kit for detecting the JAK2V617F mutation sites. According to the invention, the JAK2V617F mutation rate can be economically, simply, efficiently, sensitively, accurately and quantitatively detected, and the detection mutation rate is as low as 0.1%.

The invention discloses a novel Fc effect eliminated framework flow antibody, and belongs to the technical field of biological medicine. The antibody comprises a mutation combination of L234A, L235A, P238S and D265A in a heavy chain CH2 region, and can further comprise S267E and L328F mutations, so that the Fc receptor binding capacity is effectively reduced. The type of the antibody can be selected from multiple forms of scFv-Fc, (scFv) 2-Fc, scFv / scFv-Fc, Fab / scFv-Fc and the like. The invention also provides a nucleic acid sequence for coding the antibody and a preparation method of the antibody. The preparation method comprises the following steps: introducing specific mutation into a CH2 region of recombinant rabbit IgG, and expressing and purifying in a mammal expression system to obtain the antibody. When the antibody is applied to a flow cytometry detection reagent, a non-specific background signal caused by Fc receptor combination can be effectively eliminated, and the detection specificity and accuracy are improved.

This invention relates to the fields of molecular biology and human genetic disease detection; specifically, it relates to a reference standard for methylmalonic acidemia and its application. The reference standard comprises positive reference cells with MMACHC gene mutation sites. The genome of the positive reference cells contains one or more combinations of specific mutation sites of the following MMACHC genes: c.609G>A, c.567insT, c.658_660delAAG, c.482G>A, c.1A>G, c.80A>G, c.217C>T, c.315C>G, and c.394C>T. This reference standard provides reliable technical support for the accurate detection of methylmalonic acidemia, especially MMACHC gene-related mutations, and is of great significance in improving detection accuracy and promoting detection standardization.

To provide cancer vaccines based on a replication-defective vaccinia virus such as an MVA expressing antitumor neopeptide fusions, and to provide methods for preparing the same.SOLUTION: The present invention relates to a personalized cancer vaccine comprising a recombinant poxvirus encoding one or more neopeptides, or to a composition comprising such a recombinant poxvirus and a pharmaceutically acceptable vehicle, and to use of the personalized cancer vaccine to treat a cancer subject in need thereof. A particular embodiment is a method for providing the vaccine or composition, comprising the steps of: a) extracting DNA from tumor and non-tumor samples; b) selecting a target region, preferably the entire coding region of the genome (exome); c) sequencing the target region (e.g., the exome) from the extracted DNA; and d) identifying one or more tumor-specific mutations by comparing the DNA sequences obtained from the tumor and non-tumor samples.SELECTED DRAWING: None

Two or more peptides or polypeptides and an adjuvant for use in a method of inducing a tumor specific immune response, wherein the peptides or polypeptides have been identified by a method comprising: identifying a plurality of neoantigenic peptides for preparing a subject-specific immunogenic composition, each neoantigenic peptide comprising a tumor-specific neoepitope comprising a tumor-specific mutation, the method comprising: a. identifying a plurality of subject-specific tumor mutations in expressed genes of a subject having cancer by whole genome or whole exome nucleic acid sequencing of tumor and normal tissue samples from the subject, wherein the mutations are present in the genome of cancer cells of the subject but not in normal tissue from the subject; b. wherein when a mutation identified in step (a) is a point mutation: i. identifying a mutant peptide having the mutation identified in step (a), wherein said mutant peptide comprises a tumor-specific neoepitope which binds to a class I HLA protein with a greater affinity than a wild -type peptide; and has an IC50 less than 500 nm; c. wherein when a mutation identified in step (a) is a splice-site, frameshift, read-through or gene-fusion mutation: i. identifying a mutant polypeptide encoded by the mutation identified in step (a), wherein said mutant polypeptide comprises a tumor-specific neoepitope which binds to a class I HLA protein.

Provided in the present invention are a fatty-acid-chain-modified GLP-1-FGF21 fusion protein, and a preparation method therefor and the use thereof. In the fusion protein, after a specific mutation site is introduced at the C-terminus of FGF21, the terminus of GLP-1-FGF21 is subjected to a fatty-acid-chain modification by using a Sortase-A enzyme-mediated molecular modification technique. The fatty-acid-chain modification can achieve: extended half-life of GLP-1-FGF21; slowed terminal degradation of FGF21 by fibroblast activation protease (FAP); and low-cost operation and rapid preparation of the GLP-1-FGF21 fusion protein in an aqueous solution at room temperature. The enzyme-mediated molecular modification technique is used on the GLP-1-FGF21 fusion protein of the present invention, thereby providing significant advantages.

This invention discloses a radiotracer targeting pan-KRAS mutant proteins, its preparation method, and its applications. The tracer uses small molecule ligands that specifically recognize multiple KRAS mutant proteins as targeting modules, and is coupled to diagnostic radionuclides through an optimized linkage system. This tracer is independent of specific mutation sites and can broadly and specifically bind to multiple high-frequency KRAS mutant subtypes, including G12C, G12D, and G12V. Based on PET / SPECT imaging, this tracer enables rapid, non-invasive, systemic, visualized, and quantitative assessment of KRAS mutant protein expression load in living tumors, overcoming the invasiveness, spatiotemporal limitations, and tumor heterogeneity challenges of traditional biopsies. It provides a novel molecular imaging tool for accurate companion diagnosis of KRAS-mutant tumors, screening of patients benefiting from pan-KRAS inhibitors, and monitoring efficacy, possessing significant clinical translational value.

The present invention relates to multispecific antibody constructs comprising Fab fragments having a specific set of mutations at the interface of the CH1 and CL domains, said mutations preventing heavy / light chain mismatch.

A statistical model can be used to evaluate the potential of specific mutations to become dominant in a population of hosts by leveraging a contrast between a measure of within-host fitness and between-host fitness for a given mutation. The model can based on deep sequencing data that provides information variant frequencies within a single host. Deep sequencing across multiple hosts enables a determination of between-host detection frequency. Based on discrepancies between the within-host variant frequency and the between-host detection frequency, mutations with high fitness potential can be identified (or predicted) as potential "key" mutations before they become dominant across a host population.

The present invention relates to a mutant LC3B allosteric switch, wherein three specific residues have been mutated to either reduce or enhance receptor binding, compared to the wild- type protein. In particular, the present invention provides a method for generating conformational ensemble of lipidated protein on the membrane and introducing specific mutations within the protein activation switch that is indirectly altering protein binding pocket without disrupting its functional domains. The identification of an activation site opens avenues for the development of small molecules or peptides to enhance or regulate protein activity, providing a new dimension for therapeutic interventions. Therefore, by linking the structural insights of lipidated forms to functional outcomes, the invention advances knowledge on LC3 activity regulation, which could further be utilized to modulate the autophagy pathways.

Disclosed herein is a botulinum neurotoxin (BoNT) polypeptide with a modified receptor binding domain (HC) having one or more amino acid mutations that modify the binding of the BoNT to the receptor. Specific mutations and combinations of mutations are also disclosed. Isolated modified HC, polypeptides comprising the modified HC, chimeric molecules, pharmaceutical compositions, and methods of making and using the same are also disclosed. Methods of identifying additional such modified receptor binding domains, are further disclosed.

The application belongs to the field of genetic engineering and enzyme engineering, and discloses a kind of N-acetylneuraminic acid synthase mutant and its application in N-acetylneuraminic acid production, the mutant NeuB C86T is obtained by site-specific mutation on wild-type N-acetylneuraminic acid synthase from Neisseria meningitidis (N. meningitidis) Neisseria meningitidis The 86th amino acid is replaced from cysteine (C) to threonine (T). Through high performance liquid chromatography (HPLC) analysis of N-acetylneuraminic acid yield, the results show that, compared with wild-type enzyme, the mutant NeuB C86T The synthesis efficiency of N-acetylneuraminic acid is significantly improved by 57%, which indicates that it has potential superiority in producing N-acetylneuraminic acid.

The invention discloses a method for targeted knockout of a pig CAPN3 gene locus and application, and belongs to the technical field of gene editing engineering. A CAPN3 gene knockout method is designed on the basis of a CRISPR / Cas9 system, specifically, specific sgRNA is designed, pX459-EXON3 and pX459-EXON19 targeting plasmids are constructed, and Bama pig embryo fibroblasts are subjected to gene editing, so that a cell line capable of realizing CAPN3 gene long fragment knockout is successfully obtained, a cell line with specific mutation is obtained, and the CAPN3 gene knockout method has the advantages that the CAPN3 gene knockout method is suitable for large-scale popularization and application. The method has important application value in pig gene editing research and related fields.

The invention provides a method for increasing the drought resistance of soybean plants by introducing site-specific mutations into stomatal opening genes. The invention also relates to a soybean plant, an isolated part thereof or the seeds thereof, wherein said genes have been inactivated.

The invention belongs to the field of plant genetic breeding, and discloses a rice restorer line cadmium low-accumulation mutant gene which is based on a Nipponbare reference genome IRGSP-1. 0, and deletion mutation of a basic group CCAG occurs after a nucleotide at the 8875181 site of a chromosome 7 of rice. The cadmium low-accumulation mutant gene of the rice restorer line is derived from the rice restorer line R8022, and a gene resource library of low-cadmium rice breeding is enriched. The low-cadmium mutant is successfully created and screened in the restoring line R8022, a key parent foundation is laid for subsequent cultivation of a new hybrid rice variety with high yield, high quality and low-cadmium safety characteristics, and targeted improvement on the existing excellent genetic background is realized. According to the KASP marker primer combination specially aiming at the specific mutation and the detection method thereof, an efficient, rapid, accurate and relatively low-cost genotype identification tool is provided, the selection efficiency can be remarkably improved, and the breeding period can be shortened.

The invention provides application of K46 lactic acid of AARS2 mediated ULK1 as a target spot in preparation of an anti-kidney cancer product, so that the K46 lactic acid of the AARS2 mediated ULK1 as the target spot can be used for preparing the anti-kidney cancer product. The use comprises partial or complete knockout of AARS2 and / or ULK1 genes; the AARS2 protein activity is inhibited; the K46 gene of the ULK1 is subjected to specific mutation; the invention relates to a cell penetrating peptide aiming at a ULK1 K46 site and other methods. And inhibiting the expression of AARS2 and / or controlling the K46 lactylation level of ULK1 to play a role in resisting kidney cancer.

A recombinant antigen against Zika / Dengue virus, and a vaccine composition thereof and its use. The recombinant antigen is obtained by introducing a specific mutation into the FL fusion loop region and optionally the non-FL fusion loop region of the E protein of a wild-type Zika / Dengue virus. By introducing the specific mutation, the FL epitope of the recombinant antigen is disrupted, which can prevent the induction of antibodies against the FL epitope; thus, the purpose of reducing or eliminating the ADE effect is achieved. In addition, the recombinant antigen has the correct conformation of the E protein, has a protein expression level similar to or higher than that of a wild-type, and can induce a relatively high titer of specific binding antibodies and neutralizing antibodies in the animal body, so that effective immune protection can be provided, and good clinical application value and industrialization prospects are achieved.

Disclosed herein in one aspect is a pharmaceutical composition comprising a plurality of neoantigen peptides and a pharmaceutically acceptable carrier, each neoantigen peptide comprising a tumor-specific neoepitope capable of binding to an HLA protein in a subject, each tumor-specific neoepitope comprising a tumor-specific mutation present in a tumor, wherein (a) the composition comprises neoantigen peptides comprising tumor-specific mutations present in at least 1% of subjects in a population of subjects having cancer; (b) the composition comprises neoantigen peptides comprising tumor-specific neoepitopes that bind to an HLA protein present in at least 5% of subjects in the population; and (c) the composition comprises at least one neoantigen peptide capable of eliciting an immune response against a tumor present in at least 5% of subjects in the population of subjects having cancer.