1592 results about "Somatic cell" patented technology

The invention relates to the technical field of biological information, in particular to an immunoreaction evaluation method based on tumor neoantigen activity sorting. The method comprises the following steps: obtaining genome data of tumor and normal tissues through whole exon sequencing, extracting multi-dimensional features of candidate somatic mutation, and screening by combining a Gaussian mixture model and a Transform model to obtain a high-confidence mutation genome set; predicting the HLA genotype of a patient based on sequencing data, translating and mutating into a peptide fragment, predicting the binding affinity of the peptide fragment and an MHC molecule by using an XGBoost model, and calculating a new antigen activity score sequence in combination with various parameters; and finally, synthesizing a new antigen peptide fragment according to a sorting result, carrying out in-vitro co-culture to detect an IFN-gamma secretion result, and dynamically optimizing a characteristic combination coefficient through a PPO algorithm to realize intelligent iterative updating, so that the accuracy of new antigen screening and the immunoreaction prediction capability are remarkably improved.

The invention relates to an organ-like core-shell microsphere as well as a preparation method and application thereof. The preparation method comprises the steps that 1, raw materials are prepared, specifically, shell raw materials and inner core raw materials are prepared, the shell raw materials comprise a photoinitiator and methacrylated hyaluronic acid (HAMA), and the inner core raw materials comprise organoid precursor cell suspension and matrigel; 2) molding: extruding the dispersion phase of the shell raw material wrapping the core raw material to a continuous phase by using a micro-fluidic chip and a high-precision injection pump, cutting the dispersion phase into liquid drops by the continuous phase, and performing illumination curing on the liquid drops to form core-shell microspheres; and (3) incubating, namely culturing the core-shell microspheres in a culture medium, so that the organoid precursor cells in the inner core are developed into organoids. According to the preparation method, rapid forming and curing of the organ-like precursor cells carried by the matrigel are achieved, so that the time of the organ-like precursor cells staying in the oil phase is shortened, the cells can obtain oxygen and nutrient substances, and the cell activity is improved.

The present invention relates to a method for constructing an eight-gene-edited xenogeneic organ transplantation donor pig, belonging to the field of animal biotechnology. In the wild-type porcine fetal fibroblast cell line, the GGTA1, β4GalNT2, and CMAH genes are knocked out by using the CRISPR / Cas9 gene editing technology, and the humanized genes of hCD39, hCD46, hCD55, hCD59, and hTBM are transfected. Combining with somatic cell cloning technology, GTKO / β4GalNT2KO / CMAHKO / hCD39 / hCD46 / hCD55 / hCD59 / hTBM eight-gene-edited cloned pigs are constructed. Further, through genotype, mRNA, protein expression identification and functional analysis, eight-gene-edited xenogeneic organ transplantation donor pigs are obtained. The present invention solves the technical problems of high production difficulty, low efficiency, and low survival rate of donor pigs for multi-gene-edited xenogeneic organ transplantation, and maximally solves the common problems of immune rejection reaction and complement dysregulation faced during xenogeneic organ transplantation, laying a foundation for more targeted development of donor pigs suitable for different tissue and organ xenotransplantation, and having important value for promoting the clinical transformation of xenogeneic organ transplantation.

Disclosed are compositions and methods for preventing graft versus host disease (GVHD) in subjects receiving donor cells. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer suppress alloreactive donor cells. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of suppressing alloreactive donor cells in a subject receiving transplant donor cells that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

The present disclosure provides compositions and methods useful in the treatment of trinucleotide repeat disorders, including Huntington's disease and Friedreich's ataxia. The present disclosure also provides gRNAs designed to target the HTT or FXN genes. Complexes comprising a base editor and any of the gRNAs disclosed herein are also provided by the present disclosure. The present disclosure further provides polynucleotides, vectors, cells, compositions, and kits. Methods of treating Huntington's disease and Friedreich's ataxia are also provided herein.

Disclosed are compositions comprising a nucleic acid molecule. The nucleic acid molecule may encode an exonic sequence or portion thereof of a target ribonucleic acid (RNA) sequence. The nucleic acid molecule may further encode one or more stabilization domains. The one or more stabilization domains may be configured to reduce a cellular nuclease activity compared to a nucleic acid molecule that does not comprise the one or more stabilization domains.

The invention discloses a novel coronavirus neutralizing antibody, a detection kit and application of the novel coronavirus neutralizing antibody. The amino acid sequence of a heavy chain variable region of the neutralizing antibody is shown as SEQ ID No.1, and the amino acid sequence of a light chain variable region of the neutralizing antibody is shown as SEQ ID No.2. The antibody with mature affinity is screened through bioinformatics analysis of a single B cell, the antibody screening process is optimized by combining single cell RNA sequencing, VDJ rearrangement analysis and somatic cell hypermutation research, blindness of a traditional method is avoided, and the accuracy and effectiveness of antibody screening are improved. According to the neutralizing antibody GR12 provided by the invention, a heavy chain variable region and a light chain variable region of the neutralizing antibody GR12 can be specifically combined with an RBD structural domain of the SARS-CoV-2 and an S-Trimer structural domain of an Omicro variant, so that a broad-spectrum neutralizing effect on the SARS-CoV-2 virus and the variant thereof is realized. The binding activity of the antibody GR12 to S-Trimer and RBD under 2-fold and 300-fold dilution conditions is obviously superior to that of other antibodies, which indicates that the antibody GR12 has high affinity and dilution stability and is suitable for clinical large-dose administration.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near at least one gene that encodes a survival factor, wherein the genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor.

The invention provides a cell development process dynamic modeling method and device based on time sequence single cell transcriptome data and a medium, and relates to the crossing field of bioinformatics and computational biology. The method comprises the following steps: constructing a Shenchang differential equation learning framework; adjusting parameters of the single cell development state change model based on the Shenxuan differential equation learning framework so as to construct a population cell development state change model; obtaining a cell specific gene regulation network and a population cell gene regulation network based on the population cell development state change model so as to predict occurrence opportunity of cell lineage differentiation and a molecular decision mechanism of cell differentiation; therefore, the problems of incomplete modeling mechanism, insufficient noise processing and lack of energy principle in the existing cell development process are solved.

Disclosed are methods of augmenting efficacy of oncology therapies by providing reprogrammed cells such as personalized regenerative cells that modulate the tumor microenvironment. In one embodiment, somatic cells are dedifferentiated into OCT-4 expressing cells and endowed with tumor homing properties through culture or gene engineering. Once a stable population of tumor homing cells is established, such cells are made to express immune stimulating agents constitutively, or selectively upon entering the cancer microenvironment. Selective expression of immune stimulatory agents can be induced by exposure to hypoxia, acidosis, immune suppressive signaling or inflammatory signaling.

The invention provides a plug-and-play Mi3 protein nanocage fusion protein with a VNP6 tag and a preparation method and application of the plug-and-play Mi3 protein nanocage fusion protein, the fusion protein comprises the VNP6 tag, a SpyCatch003 component, a Mi3 protein nanocage and a functional protein sequence, and the VNP6 tag is located at the N end of the fusion protein. The VNP6 peptide sequence or the variant thereof is utilized to induce a vesicle or vesicle-like structure beneficial to protein folding and stabilization in escherichia coli, so that the correct folding rate and activity of recombinant protein are improved while the overall intracellular molecular crowding effect is relieved. The core idea of the invention lies in that the internal structure of cells is regulated at low temperature, and the internal microenvironment of an escherichia coli expression system is optimized, so that protein molecules under high expression load can obtain more reasonable spatial distribution, and the problems of misfolding and aggregation caused by molecular crowding are reduced.

Methods, systems, and software for estimating circulating tumor fraction are provided. A first plurality of nucleic acid sequences for a plurality of loci in genomic DNA from a solid tumor sample is obtained. A second plurality of nucleic acid sequences for a plurality of cell-free DNA fragments obtained from a liquid biopsy sample from the same subject is obtained. One or more somatic mutations is identified in the first plurality of nucleic acid sequences. A variant allele frequency (VAF) is determined for each somatic mutation based on a frequency of the respective somatic mutation in the liquid biopsy sample and a frequency of the corresponding wild type allele in the liquid biopsy sample, thereby determining a set of VAFs. An estimate of the circulating tumor fraction for the test subject is determined based on the set of VAFs for the one or more somatic mutations.

The invention discloses a novel coronavirus neutralizing antibody, a detection kit and application of the novel coronavirus neutralizing antibody. The amino acid sequence of a heavy chain variable region of the neutralizing antibody is shown as SEQ ID No.1, and the amino acid sequence of a light chain variable region of the neutralizing antibody is shown as SEQ ID No.2. The antibody with mature affinity is screened through bioinformatics analysis of a single B cell, the antibody screening process is optimized by combining single cell RNA sequencing, VDJ rearrangement analysis and somatic cell hypermutation research, blindness of a traditional method is avoided, and the accuracy and effectiveness of antibody screening are improved. According to the neutralizing antibody GR75 provided by the invention, a heavy chain variable region and a light chain variable region of the neutralizing antibody GR75 can be specifically combined with an RBD structural domain of the SARS-CoV-2 and an S-Trimer structural domain of an Omicro variant, so that a broad-spectrum neutralizing effect on the SARS-CoV-2 virus and the variant thereof is realized. The binding activity of the antibody GR75 to S-Trimer and RBD under 2-fold and 300-fold dilution conditions is obviously superior to that of other antibodies, which indicates that the antibody GR75 has high affinity and dilution stability and is suitable for clinical large-dose administration.

The invention focuses on the fields of biotechnology and sanitary disinfection, and successfully separates five brand-new small molecule peptides (small molecule peptides K, L, M, N and O) from herba violae and spica prunellae. According to the innovative extraction method from raw material pretreatment, mixed extraction to multi-step purification, a disinfection action mechanism of destroying pathogen cell membranes, interfering energy metabolism and inhibiting biosynthesis by small molecular peptides is defined. The small molecule peptides show the advantages of efficient disinfection activity, high safety, good stability and difficult generation of drug resistance. On the basis, a series of products such as hygienic disinfection spray, wet tissues and hand sanitizer are developed, the market application prospect is wide, remarkable economic and social benefits can be brought, and a brand-new and high-quality solution is provided for the field of hygienic disinfection.

The invention discloses a novel coronavirus neutralizing antibody GR46, a detection kit and application of the novel coronavirus neutralizing antibody GR46. The amino acid sequence of a heavy chain variable region of the neutralizing antibody is shown as SEQ ID No.1, and the amino acid sequence of a light chain variable region of the neutralizing antibody is shown as SEQ ID No.2. The antibody with mature affinity is screened through bioinformatics analysis of a single B cell, the antibody screening process is optimized by combining single cell RNA sequencing, VDJ rearrangement analysis and somatic cell hypermutation research, blindness of a traditional method is avoided, and the accuracy and effectiveness of antibody screening are improved. According to the neutralizing antibody GR46 provided by the invention, a heavy chain variable region and a light chain variable region of the neutralizing antibody GR46 can be specifically combined with an RBD structural domain of the SARS-CoV-2 and an S-Trimer structural domain of an Omicro variant, so that a broad-spectrum neutralizing effect on the SARS-CoV-2 virus and the variant thereof is realized. The binding activity of the antibody GR46 to S-Trimer and RBD under 2-time and 300-time dilution conditions is obviously superior to that of other antibodies, which indicates that the antibody GR46 has high affinity and dilution stability and is suitable for clinical large-dose administration.

The invention discloses an anti-neurodegeneration exosome composition as well as a preparation method and application thereof. The anti-neurodegeneration exosome composition is prepared from the following components in parts by mass: 5 to 25 parts of human exfoliated deciduous tooth stem cell exosome, 25 to 85 parts of plant-derived exosome-like nano-vesicles, 12 to 10 parts of ginsenoside Rg, 2 to 10 parts of curcumin and 10 to 20 parts of auxiliary materials. The anti-neurodegeneration exosome composition contains a large amount of cell factors, growth factors, miRNA, mRNAs and other components, is easy to fuse with cell membranes of intestinal epithelial cells, can selectively deliver bioactive substances to recipient cells through a blood-brain barrier, carries out information transmission among different cells, regulates signal transduction among the cells, and has a good anti-neurodegeneration effect. The effects of resisting oxidation, resisting inflammation, resisting aging and the like are achieved.

Disclosed in the present invention are a monoclonal antibody against an interleukin-6 protein and the use thereof. The present invention provides a nucleic acid molecule, a vector, a cell, a composition, a product, a bispecific antibody, a CAR, an antibody-drug conjugate and a pharmaceutical composition comprising an anti-IL-6 monoclonal antibody or an antigen-binding fragment thereof; and further provides the use of the monoclonal antibody or the antigen-binding fragment thereof, the nucleic acid molecule, the vector, the cell, the composition and the product in the detection of IL-6 or a nucleic acid fragment encoding same, in the preparation of a product for detecting IL-6, in a pharmaceutical composition for preventing or treating diseases related to abnormal IL-6 expression, and in the preparation of a pharmaceutical composition for regulating the expression level or activity of IL-6.

The present disclosure relates to methods for detecting unique genetic signatures derived from markers such as, for example, mutations, somatic or germ-line, in nucleic acids obtained from biological samples. The sensitivity of the methods provides for detection of mutations associated with a disease, e.g., cancer mutations, or with inherited disease, e.g., an autosomal recessive disease, in a noninvasive manner at ultra-low proportions of sequences carrying mutations to sequences carrying normal, e.g., non-cancer sequences, or a reference sequence, e.g., a human reference genome.

Provided herein are engineered immune cells and populations thereof for administration to patients to treat cancer (e.g., solid tumors or liquid tumors) and other conditions. The cells are engineered to functionally express a reduced level of one or more of RFX5, NLRC5, TAP2, β2m, TRAC, RFXAP, CIITA and RFXANK. The cells optionally are further engineered to express one or more than one additional protein such as an antigen binding protein (e.g., a chimeric antigen receptor (CAR) or T cell receptor) to target tumor cells or other damaged cells in the patient and / or to express other genes at a reduced level. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering the cells and the compositions.

The invention provides an AbAIL5 gene and application of the AbAIL5 gene in improvement of genetic transformation efficiency of amorphophallus bulbifer, and belongs to the technical field of biology. The invention provides an AbAIL5 gene. The nucleotide sequence of the AbAIL5 gene is shown as SEQ ID NO: 1. Genetic transformation is performed on the amorphophallus bulbifer somatic embryo by constructing an overexpression vector of the AbAIL5 gene, so that the genetic transformation efficiency of the amorphophallus bulbifer callus can be improved, and candidate genes are provided for application of a large-scale breeding technology and a genetic transformation technology of the amorphophallus bulbifer callus in good varieties.

We introduce a variant classifier that uses trained deep neural networks to predict whether a given variant is somatic or germline. Our model has two deep neural networks: a convolutional neural network (CNN) and a fully-connected neural network (FCNN), and two inputs: a DNA sequence with a variant and a set of metadata features correlated with the variant. The metadata features represent the variant's mutation characteristics, read mapping statistics, and occurrence frequency. The CNN processes the DNA sequence and produces an intermediate convolved feature. A feature sequence is derived by concatenating the metadata features with the intermediate convolved feature. The FCNN processes the feature sequence and produces probabilities for the variant being somatic, germline, or noise. A transfer learning strategy is used to train the model on two mutation datasets. Results establish advantages and superiority of our model over traditional classifiers.

An antigen peptide is provided specifically for treating individuals suffering from ovarian cancer, preferably based on BRCA1 gene c. 5470_5477del8 mutation. It is selected from amino acid sequences of SEQ ID NO. 1 to SEQ ID NO. 6, or derived by substitution, deletion and / or addition of at least one amino acid. The neoantigen polypeptides of the present disclosure can significantly activate T lymphocytes specific to the BRCA1 gene c. 5470_5477del8 mutation in vitro, stimulating the release of the cytokine IFN-y, indicating notable immunogenicity. This enhances T lymphocytes' ability to target and kill cancer cells from ovarian cancer patients carrying the BRCA1 gene c. 5470_5477del8 mutation. Additionally, the antigen peptide can activate and expand human T lymphocytes specific to the BRCA1 gene c. 5470_5477del8 mutation in vitro for adoptive cell therapy. The antigen peptide of the present disclosure addresses the gap in personalized antigen peptide therapies for ovarian cancer patients with BRCAl-c. 5470_5477del8 somatic mutations.

The present disclosure relates to cellular compositions that are modified to introduce a nucleic acid or vector expressing the same. Such compositions may be used to deliver nucleic acid to a target cell and treat disease such as cancer.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating the genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near at least one gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or component or transcriptional regulator of the MHC-I or MHC-II complex, at least one genetic modification that increases the expression of at least one polynucleotide that encodes a tolerogenic factor, and optionally at least one genetic modification that increases or decreases the expression of at least one gene that encodes a survival factor.

The invention relates to the field of image processors and biological medicines, and discloses an NK cell activity rapid detection method based on image processing. The method comprises the following steps: acquiring an unmarked time sequence phase image sequence of an NK cell and target cell co-culture system; performing cell instance segmentation to track individual cells; extracting a morphological dynamic characteristic parameter set of the target cell, wherein the morphological dynamic characteristic parameter set comprises a volume change rate, a phase gradient entropy, a cytoplasm phase fluctuation frequency and a nuclear region phase mean value; inputting the parameters into a pre-trained death state discrimination model, and outputting a death probability; and calculating a killing efficiency index based on the death probability evolution curve, and judging the activity level of the NK cells. The system comprises a phase image acquisition unit, a cell segmentation unit, a feature extraction unit, a death judgment unit and an activity judgment unit. Through unmarked imaging and deep learning fusion analysis, high-precision, real-time, quantitative and ultra-early NK cell activity evaluation is realized, and the method is suitable for clinical instant inspection and immunotherapy monitoring.

The invention discloses a composite microecological preparation as well as a preparation method and application thereof. The compound microecological preparation disclosed by the invention comprises lactobacillus casei, lactobacillus plantarum and saccharomyces cerevisiae. The application effect of the composite microecological preparation in cow breeding is remarkable, the optimal addition amount of the composite microecological preparation is 100 mL / cow / day, the production performance of lactating cows can be improved, the milk yield is improved by 3.30 kg / cow / day, the milk yield of 4% standard milk is improved by 3.78 kg / cow / day, the total protein is improved by 15.9%, the albumin is improved by 14.7%, the globulin is improved by 16.5%, and the somatic cell number is reduced by 52.6%; and pollutant emission can be reduced, including 37.2% of ammonia emission reduction and 28.7% of carbon dioxide emission reduction.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating the genetically modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near at least one gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or component or transcriptional regulator of the MHC-I or MHC-II complex, at least one genetic modification that increases the expression of at least one polynucleotide that encodes a tolerogenic factor, and optionally at least one genetic modification that increases or decreases the expression of at least one gene that encodes a survival factor.

The invention provides a novel D-A-D type fluorescent probe material as well as a preparation method and application thereof. The fluorescent probe material has good stability, the preparation process is simple, and the synthesis condition is mild. Moreover, the D-A-D type fluorescent probe material has good solubility and stability, and a complex of the D-A-D type fluorescent probe material and zinc ions can identify pyrophosphate ions with high selectivity and high sensitivity. The interference of phosphate ions, hydrogen phosphate ions, dihydrogen phosphate ions, fluorine ions, chloride ions, nitrate ions, acetate ions, sulfate ions and carbonate ions is avoided; after the zinc ion complex of the D-A-D type fluorescent probe material is combined with PPi, the fluorescence intensity is remarkably enhanced, the D-A-D type fluorescent probe material has a higher signal-to-noise ratio, in-situ imaging detection of a target object in living cells or tissues is realized, the defects of a traditional molecule and ion detection method are overcome, and the D-A-D type fluorescent probe material is suitable for being widely applied to the field of biological imaging. # imgabs0 #

The invention provides application of a CD47 gene in detection of pig litter size phenotype and application of an SNP site of the CD47 gene in gene expression regulation. It is found that the CD47 gene is regulated and controlled by the SNP site rs323354626, it is further found that the rs323354626 site and the phenotype of the total litter size of sows show the highest significance, and it is indicated that the CD47 gene and the total litter size of the sows have large correlation. In three main commercial varieties of pigs, namely Duroc, Landrace and Yorkshire, the CD47 expression level in testis tissues is negatively correlated with the litter size, which indicates that the expression mode of the CD47 gene may influence the reproductive performance of the pigs, and the litter size phenotype of the pigs can be detected by detecting the CD47 gene expression level in the testis of the breeding pigs or somatic cells of the sows. Or the litter size of the pigs is influenced by regulating and controlling the expression level of the CD47 gene through the rs323354626 site, and the discovery lays a foundation for improving the breeding efficiency of the pigs, especially for a breeding method for increasing the litter size.

The present invention relates to a hybrid exosome formed by the fusion of a human cell-derived exosome and an artificial exosome. When an active ingredient labeled with a fluorescent material was attached or encapsulated in the hybrid exosome of the present invention and applied to cells, the active ingredient was observed in the cells. In addition, when the exosome was applied to skin tissue, fluorescence expression could also be observed in the dermal layer. Therefore, the hybrid exosome according to the present invention can be used as a novel drug delivery system.