1159 results about "Somatic cell" patented technology

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.

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.

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.

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.

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.

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.

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.

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.

The disclosure provides a method for treating a subject afflicted with a tumor derived from a small cell lung cancer (SCLC) having a high tumor mutational burden (TMB) status comprising administering to the subject a monotherapy comprising an anti-PD-1 antibody or a combination therapy comprising an anti-PD-1 antibody and an anti-CTLA-4 antibody. The present disclosure also provides a method for identifying a subject suitable for treatment with an anti-PD-1 antibody or a combination therapy comprising an anti-PD-1 antibody and an anti-CTLA-4 antibody comprising measuring a TMB status of a biological sample of the subject. A high TMB status identifies the patient as suitable for treatment with an anti-PD-1 antibody or antigen-binding portion thereof. The TMB status can be determined by sequencing nucleic acids in the tumor and identifying a genomic alteration, e.g., a somatic nonsynonymous mutation, in the sequenced nucleic acids.

The present disclosure relates generally to methods of inhibiting a tripartite VAP-A, ORP3 and Rab7 (VOR) protein complex in multicellular organisms, to methods of identifying agents which inhibit such complex and to the medical use of those agents. Inhibition of the VOR complex causes interference with at least one mechanism of intercellular communication, wherein the intercellular communication is mediated by receptor-ligand interaction and / or EVs, and viral infection involving the transport of endocytosed biomaterials to the nucleus of recipient cells.

The present invention encompasses compositions and methods to allow one to deliver and express multiple genes under the control of multiple gene regulatory components in a recipient cell via a synthetic chromosome. The engineering of synthetic chromosomes to contain multiple gene control units permits the construction of complex biological circuits.

The invention belongs to the technical field of biomedicine, and relates to a method for constructing a mouse embryo-derived hypothalamic organ model and application, the invention proposes that a mouse embryo is used for constructing a hypothalamic organ for the first time, and the mouse embryo has a definite development time sequence and genetic operability; the naturally retained vascular endothelial cells and multilineage precursor cells provide unique advantages for constructing a three-dimensional organ containing multiple nucleuses such as a preoptic region, a paraventricular nucleus, an arcuate nucleus and a supraoptic nucleus, and the model not only breaks through the nucleus coverage limitation of the existing iPSCs organ, but also can be used for constructing the three-dimensional organ containing multiple nucleuses such as the preoptic region, the paraventricular nucleus, the arcuate nucleus, the supraoptic nucleus and the like by reconstructing a nerve-blood vessel unit. High-fidelity simulation of complex physiological functions of the hypothalamus is realized, and an irreplaceable technical platform is provided for mechanism analysis of neuroendocrine diseases and high-throughput screening of drugs.

Several embodiments disclosed herein relate to methods and compositions for enhanced expansion of NK cells in culture, through the repeated co-culturing of NK cells with feeder cells and the selective use of stimulatory interleukins. In several embodiments, the methods utilize one or more soluble interleukins as culture media supplements at one or more time points during expansion of the NK cell, or other immune cell, which results in a highly expanded and highly cytotoxic population of cells, for use in, for example allogeneic cellular immunotherapy.

The invention discloses a conjugational transfer-assisted orthogonal targeted mutation evolution system, which comprises a donor strain and a receptor strain, a donor strain intracellular muter performs targeted mutation on a target sequence to obtain a mutation sequence, a non-self-transferable conjugational transfer functional plasmid is introduced into the donor strain, and a non-self-transferable conjugational transfer functional plasmid is introduced into the receptor strain. The mutant sequence is unidirectionally and horizontally transferred from a donor strain cell to a receptor strain cell, and the complete orthogonality of the mutants in the initial donor strain and the mutant sequence in the receptor strain is realized through the orthogonality between the donor strain and the receptor strain. The results of a sacB-sucrose reverse screening experiment show that the mutation frequency of an ortho-MutaT7 system reaches 2.96 * 10 <-2 > at 96 hours, which is 1840.9 times of the natural mutation frequency of the sacB in donor cells, and the ortho-MutaT7 system generates mutation of 12 basic group change types in a target sequence. The Ortho-MutaT7 system developed by the invention realizes mutation diversity and also has orthogonality, leakage mutation and off-target mutation of mutants in host cells are fully avoided, and a direct relationship between a mutation sequence and a phenotype is established.

The invention discloses a chicken myoblast and chicken fat precursor cell co-culture synchronous differentiation method and application thereof, and belongs to the technical field of animal cell co-culture and differentiation. The method comprises the following steps: respectively carrying out in-vitro multiplication culture on chicken myoblasts and chicken fat precursor cells, carrying out mixed co-culture, inducing for at most two days by adopting horse serum with the volume percent of 0.5-2%, carrying out pre-differentiation, and continuously carrying out induced differentiation culture for at most one day by using an induced adipogenesis culture medium. According to the synchronous differentiation method for co-culture of the chicken myoblasts and the chicken fat precursor cells, a cell co-culture system is constructed, time sequence induced differentiation is achieved, and a final product with fat droplets distributed in the gaps of muscle bundles (the average distance is 20-50 microns) and capable of recarving natural chicken intermuscular fat textures is obtained. According to the method, the differentiation period is shortened to be within 3 days from 21 days (the efficiency is improved by 600%); the induction cost is reduced by 42.7%; the final product breaks through the sensory acceptance barrier through bionic structure recarving.

Disclosed in the present invention is an siRNA for inhibiting the expression of a urate transporter 1 (URAT1) gene in human cells. In the present invention, a plurality of siRNAs capable of inhibiting URAT1 expression are obtained by screening, and on this basis, appropriate modifications are performed to obtain sequences with improved target silencing ability. Drugs with the siRNAs as active ingredients are expected to be clinically applicable in the prevention and treatment of diseases related to the URAT1 target, such as gout, hyperuricemia, gouty arthritis and renal calculi.

The invention relates to the field of gene engineering, in particular to Os HSL mutants and coding genes, expression vectors, transgenic cells, compositions and application thereof, the mutants are Os HSL1 enzyme and / or Os HSL2 enzyme mutants, the amino acid sequence of the Os HSL1 enzyme is as shown in SEQ ID NO.1, and the amino acid sequence of the Os HSL2 enzyme is as shown in SEQ ID NO.2. The invention further relates to an application of the Os HSL mutants and the coding genes, the expression vectors, the transgenic cells and the compositions. The invention relates to a gene, a protein, a carrier, a cell and a composition which endow plants with a detoxification effect on an HPPD inhibitor and application of the gene, the protein, the carrier, the cell and the composition to plant improvement, so that the plants are endowed with resistance to the HPPD inhibitor.

The invention discloses a medicine composition for inducing fibroblasts to be reprogrammed into pericyte-like cells (PCLCs) through a chemical small molecule combination, and the medicine composition is used for treating sepsis. According to the invention, a chemical reprogramming strategy without genetic modification is adopted, an endogenous signal channel is activated through a time sequence, and fibroblasts from somatic cells are efficiently converted into PCLCs with high expression of genes such as EMILIN3, LAMC3, GDF10, AHR, CD109, AHR, NQO1, QPRT and the like. When applied to treatment of sepsis, the medicine composition can improve pathological symptoms and reduce death rate by synergistically exerting anti-inflammatory, anti-oxidation, immune regulation and tissue barrier protection effects. The invention provides a novel safe treatment strategy based on non-genetically modified cells for sepsis.

The invention relates to the technical field of hyperbaric oxygen physiotherapy cabins, in particular to a terahertz wave micro hyperbaric oxygen physiotherapy cabin which comprises a cabin body, a door opening is formed in one face of the cabin body, a cabin top is installed at the top of the cabin body, and a door plate is hinged to the interior of the door opening through a hinge; the deep sea volcanic energy stone treatment device comprises a cabin, two groups of bed bodies are arranged in the cabin, the two groups of bed bodies are symmetrically mounted in the cabin, each bed body is of a hollow structure, and a plurality of terahertz wave generation modules are uniformly laid on the upper surface of each bed body through a support. The pelelith-based passive terahertz releaser formed after the pelelith-based passive terahertz releaser is combined with the ceramic matrix can continuously release terahertz waves with the frequency band of 0.1-12 THz, the vibration frequency is consistent with that of human cells, and the terahertz waves with the frequency band can repair biological enzyme and nucleic acid structure deformation caused by free radical attack and age increase through the biological resonance effect, so that the pelelith-based passive terahertz releaser can be used for repairing biological enzyme and nucleic acid structure deformation caused by free radical attack and age increase. The metabolic function is recovered from the cell molecule level, and the defect that a traditional oxygen cabin can only supply oxygen on the surface layer and cannot be deeply repaired is overcome.

The invention discloses a cell lineage tracking system based on synNotch and CRISPR / Cas9 bar code technology and application thereof, the cell lineage tracking system comprises a system mGFP ligand vector for constructing Sender ligand cells and a system for constructing Receiver recipient cells, and the system comprises a synNotch receptor-rtTA fusion vector, a TetO-Cas9 expression vector, a gRNA expression vector and a Target vector library containing a Barcode sequence. A synNotch system and a CRISPR / Cas9 gene editing technology are combined with a bar code strategy, a unique bar code is generated, the contact sequence between cells is recorded, the method is compatible with a single-cell sequencing technology, transcription information of the cells is provided, long-term tracking of the contact history between the cells is achieved, the method can be used for tracking interaction and functions between the cells in a tumor microenvironment, and the application prospect is wide. Through long-term tracking and functional analysis of interaction between macrophages, especially macrophages and tumor cells, the accuracy of interaction analysis is remarkably improved, and a more accurate target spot is provided for targeted therapy.

The invention specifically discloses three SNP (Single Nucleotide Polymorphism) molecular markers obviously related to Chinese Holstein cattle somatic cell scoring (SCS) and application thereof. The SNP is located in the following aspects: 1) in a No.8 chromosome 15818198bp (LINGO2 gene, Ggt; t), genotype effect GGlt; gTlt; GTlt; tT; 2), in the 17th chromosome 16535314bp (Ggt in the ZNF330 gene; a), effect GGlt; aA1t; AA1t; gA; 3) in the 69672126bp (in the PACS2 gene, Ggt; a), effect GGlt; gAlt; aA. SCS is an index of mastitis, and high SCS corresponds to high morbidity rate of mastitis. By detecting the genotypes of the sites, individuals with low SCS (namely, low mastitis morbidity) can be accurately bred in the early stage, the disease-resistant breeding efficiency and accuracy are remarkably improved, the reduction of the mastitis morbidity of groups is accelerated, and the production performance and economic benefits are improved.

Disclosed are in vitro methods for the differentiation of precursor cells into a neural crest cell (NCC) primed to a neurogenic lineage. The methods may include, for example, the steps of activating a Hedgehog signaling pathway (“HH signaling pathway”) in a precursor cell, wherein the precursor cell may be contacted with a neural crest cell induction medium for differentiation of the precursor cell into a neural crest cell. Compositions for carrying out the disclosed methods are also disclosed.

The invention belongs to the field of medicine, and discloses application of POCM-NP-coated A939572 in preparation of a medicine for treating osteoporosis, the POCM-NP-coated A939572 comprises osteoclast precursor cell membrane vesicles and NP-coated A939572 loaded on the osteoclast precursor cell membrane vesicles, and the NP-coated A939572 is PLGA (poly (lactic-co-glycolic acid)) nanoparticles entrapped with the NP-coated A939572. The POCM-NP-coated A939572 obtained by loading the nanoparticles loaded with the A939572 small molecule medicine into the osteoclast precursor cell membrane vesicles has the effect of relieving the osteoporosis, can inhibit osteoclast differentiation and can be used for preventing, treating and relieving the osteoporosis.

The invention relates to a new technology for promoting generation of hematopoietic precursor cells from human pluripotent stem cells. Specifically, the present invention relates to a method for preparing hematopoietic precursor cells comprising reducing the expression level of YTHDF2 gene in pluripotent stem cells or reducing the activity of YTHDF2 protein of pluripotent stem cells. On the other hand, the invention also relates to a kit for preparing the hematopoietic precursor cell, and the kit comprises a reagent for reducing the expression level of the YTHDF2 gene or a reagent for reducing the activity of the YTHDF2 protein.

Compounds, compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo. Also disclosed are pharmaceutical compositions comprising a Cbl-b inhibitor and a cancer vaccine, as well as methods for treating cancer using a Cbl-b inhibitor and a cancer vaccine; and pharmaceutical compositions comprising a Cbl-b inhibitor and an oncolytic virus, as well as methods for treating cancer using a Cbl-b inhibitor and an oncolytic virus.

The invention discloses an NK cell culture solution and an NK cell culture. The culture solution comprises a cell activation culture solution and a cell amplification culture solution, the cell activation culture solution comprises a basic culture medium, and the basic culture medium contains autologous plasma with the final concentration of 1-10%, IL-2 with the final concentration of 50-1000U / mL, IL-15 with the final concentration of 1-15ng / mL, OK432 with the final concentration of 0.1-1ug / mL and ginseng exosome with the final concentration of 1-10ug / mL; the cell amplification culture solution comprises a basic culture medium, and the basic culture medium contains IL-2 with the final concentration of 100-2000U / mL. The ginseng exosome component in the cell culture fluid can promote NK cell proliferation and remarkably improve the immune killing function of the NK cells, and the ginseng exosome serving as an activating factor can effectively improve the activity of the NK cells and enhance the immune effect of the NK cells.