179 results about "Immune rejection" patented technology

The invention provides sgRNA for targeting and guiding nuclease to efficiently cut an HLA-DRA gene, a method for modifying a CAR-T cell by using the sgRNA, and a related gene editing system, reagent and kit. According to the CAR-T cell, the immunogenicity is greatly reduced, the risk of graft versus host disease and immunological rejection can be effectively reduced, and meanwhile the killing capacity of tumor cells of the CAR-T cell is not affected.

The invention provides sgRNA for targeting and guiding nuclease to efficiently cut a B2M gene, a method for modifying cells by using the sgRNA, and a related gene editing system, reagent and kit. The cells produced by the invention greatly reduce the immunogenicity, can effectively reduce the risk of graft versus host disease and immunological rejection, and does not affect the killing ability of the cells to tumor cells.

The invention relates to a method for carrying out gene editing on a TRAC gene locus. Specifically, the invention provides sgRNA targeting and guiding nuclease to efficiently cut a TRAC gene, a method for modifying a CAR-T cell by using the sgRNA, the CAR-T cell obtained by the method, and a related gene editing system, reagent and kit. According to the CAR-T cell, the immunogenicity is reduced, the risk of graft versus host disease and immunological rejection can be effectively reduced, and meanwhile the killing capacity of tumor cells of the CAR-T cell is not affected.

Disclosed herein are universal donor stem cells and related methods of their use and production. The universal donor stem cells disclosed herein are useful for overcoming the immune rejection in cell-based transplantation therapies. In certain embodiments, the universal donor stem cells disclosed herein do not express one or more MHC-I and MHC-II human leukocyte antigens. Similarly, in certain embodiments, the universal donor stem cells disclosed herein do not express one or more human leukocyte antigens (e.g., HLA-A, HLA-B and / or HLA-C) corresponding to MHC-I and MHC-II human leukocyte antigens, thereby rendering such cells hypoimmunogenic.

The invention relates to the technical field of synthetic biology, in particular to polypeptide with a triple helix structure, recombinant XII type humanized collagen and application of the recombinant XII type humanized collagen. The recombinant XII type humanized collagen is successfully expressed and prepared, has a triple-helix structure and good biological activity including promotion of cell proliferation activity, cell adhesion activity and inhibition of MMP-1, is used as a biological material derived from a human body, does not generate immunological rejection and anaphylactic reaction when applied to the human body, and has a good application prospect. The composition can be used for medical or non-medical application of a plurality of tissues and organs of a human body, filling, compatibilizing or repairing, and promotion of skin compactness or wrinkle resistance and other scenes.

The invention discloses application of a 3D hypoxia mesenchymal stem cell derived exosome preparation in preparation of an immune cell proliferation inhibitor or a medicine for treating acute myocardial infarction, belongs to the technical field of biology, and solves the problems of low cell survival rate and immunological rejection in application of a cell treatment method in the prior art. The 3D hypoxia mesenchymal stem cell derived exosome is used as a medium for treating acute myocardial infarction, and the problem of immunological rejection can be solved.

The invention relates to the technical field of biomedical material modification, in particular to a sulfhydrylation biocompatible polymer derivative, a preparation method thereof, extracellular matrix imitating injectable in-situ cross-linked hydrogel and application thereof. According to the invention, a pre-acylation strategy is firstly carried out on the biocompatible polymer containing both amino and carboxyl, so that a three-dimensional cross-linked byproduct formed by coupling of self amido bonds is avoided, meanwhile, the number of side chain carboxyl for sulfhydrylation modification is increased, and the accurate and adjustable pre-acylation rate can optimize the physical and chemical properties of the derivative; meanwhile, a disulfide bond is used as a protective precursor, active sulfydryl is introduced through amido bond coupling, self-oxidation of the active sulfydryl in the reaction process is avoided, sulfydryl activity is guaranteed, hydrazine-containing reagents are avoided, safety is further improved, virus residues and immunological rejection risks are avoided, universality is high, and the application prospect is wide; and in combination with a high-concentration preparation method, the method has the advantage of large-scale production, and further widens the industrial application potential.

The invention discloses a preparation method and application of collagen derivative and polysaccharide substance compounded self-gel hemostatic powder, and relates to the field of biomedical materials. Aminated collagen derivatives and aldehyde polysaccharide substances are subjected to a Schiff base reaction through amino groups and aldehyde groups; further obtaining the Schiff base cross-linked aminated collagen derivative-aldehyde polysaccharide hydrogel, freeze-drying, and grinding into powder, so as to obtain the self-gel hemostatic powder. The self-gel hemostatic powder disclosed by the invention forms hydrogel in a wound tissue for adhesion and sealing, so that rapid hemostasis is realized, postoperative adhesion at the wound tissue is avoided, and healing of a wound is facilitated; after hemostasis is completed, the self-gel powder can be dissociated and removed from the tissue surface, and the risk that thrombus is formed and immunological rejection is caused is reduced; after hemostasis is completed, the hemostasis powder can be metabolized and absorbed by a human body along with thrombus, so that the residue of the hemostasis powder in the body is reduced, and the safety is improved.

The invention relates to the technical field of biology, and particularly discloses polypeptide, recombinant XIX type humanized collagen and application of the recombinant XIX type humanized collagen. The amino acid sequence of the polypeptide comprises n repetitive units; the repetitive unit comprises any one of the following amino acid sequences or variant sequences thereof: (1) an amino acid sequence as shown in any one of SEQ ID NO.1-2; (2) an amino acid sequence having at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with the amino acid sequence as shown in any one of SEQ ID NO.1-2; (3) a variant sequence obtained by performing mutation of one or more amino acid residues on the amino acid sequence as shown in any one of SEQ ID NO.1-2; wherein n is an integer greater than or equal to 1. The polypeptide provided by the invention has a collagen triple helix structure, has good cell adhesion activity, can carry out functions of human collagen, is free of immunological rejection and anaphylactic reaction, and can be used in various fields of cartilage repair, biological dressing, tissue filling and the like.

The invention relates to the technical field of bone tissue engineering and regenerative medicine, and discloses a stem cell-loaded bionic bone scaffold material, which comprises a bone scaffold main body, the bone scaffold main body is formed by compounding hydroxyapatite and a biodegradable high-molecular polymer and has a porous structure, the porosity is 70%-90%, the aperture range is 100-500 microns, and pores are communicated with one another; a vascularization induction factor slow release system is arranged in the porous structure of the bone scaffold main body, the stem cell-loaded bionic bone scaffold material does not need to take the autologous bone of a patient, and the problems of donor injury and limited sources are avoided; the composite scaffold is matched with low-immunogenicity stem cells, so that the risks of immunological rejection and disease transmission are avoided; the material has the advantages of good biocompatibility, mechanical matching with human bones, degradability, no secondary operation, promotion of vascular regeneration and stem cell osteogenesis, and realization of bone regeneration integration.

The invention discloses a culture medium for adipose-derived stem cells, and particularly relates to the technical field of stem cell culture. The culture medium comprises a basic culture medium and nerve-vascular niche components, wherein the basic culture medium comprises DMEM / F12, 10% of human-derived platelet lysate and 1% of antibiotic solution; the nerve-vascular niche comprises the following components: a Slit3 recombinant protein, a nerve growth factor-beta, a glial cell-derived neurotrophic factor, a lysyl oxidase inhibitor, dexamethasone, 3-isobutyl-1-methylxanthine and insulin. The traditional fetal calf serum is replaced by the human-derived platelet lysate, so that the risks of immunological rejection and pathogen pollution are avoided; through the synergistic effect of nerve-vessel niche factors, blood vessel maturation and innervation are promoted, programmed mechanical stretching culture is combined, the adipogenic differentiation efficiency of adipose-derived stem cells is remarkably improved, and engineered adipose tissue which is huge in lipid droplet, compact in structure and provided with a nerve-vessel network is formed.

The invention relates to hydrogel for promoting healing of diabetic wounds as well as a preparation method and application of the hydrogel, and belongs to the technical field of hydrogel dressings. The invention discloses an exosome hydrogel, which is characterized in that exosome is loaded in crosslinked aldehyde hyaluronic acid and carboxymethyl chitosan, the aldehyde hyaluronic acid is grafted with L-arginine, and the exosome is derived from bone marrow mesenchymal stem cells. L-arginine can release nitric oxide under the action of a diabetic wound surface or an inflammation microenvironment to achieve the effects of resisting bacteria and promoting wound surface recovery, and the exosome successfully avoids the risks of cell survival defects, vascular embolism, immunological rejection and the like while retaining powerful bioactive components. The product has excellent antibacterial activity, degradability, tissue adhesion, injectable performance and self-repairing performance, and can be suitable for wounds in different shapes.

The application belongs to the technical field of biomedical materials, and discloses a collagen-based double-network porous hydrogel scaffold capable of recruiting endogenous stem cells and a construction method and application thereof. The scaffold takes collagen II (Col-II) and oxidized methyl acrylated hyaluronic acid (AHAMA) as an organic phase, and is constructed into a physical / chemical double-network structure through Schiff base dynamic crosslinking and ultraviolet light-induced methacryl radical polymerization. An air-in-water emulsion template method is used to form a through-porous structure, and 5' aldehyde-modified nucleic acid aptamer Apt19S is anchored in the scaffold network to achieve specific recruitment of endogenous pluripotent stem cells. The scaffold has excellent mechanical properties, a biomimetic extracellular matrix microenvironment and a targeted stem cell recruitment function, can effectively promote the directional differentiation of stem cells into chondrocytes, avoids the immune rejection and ethical issues caused by exogenous stem cell transplantation, and is suitable for the field of articular cartilage defect repair.

The invention provides a universal UCMSC and a construction method and application thereof.The construction method includes the steps that a UCMSC specific lipid mixture containing ionizable lipid, auxiliary lipid, a stabilizer and cholesterol is prepared, the UCMSC specific lipid mixture is mixed with a nucleic acid solution containing CRISPRoff mRNA and a targeted B2M gene super enhancer sgRNA, and UCMSC specific LNP is prepared; the optimal universal UCMSC disclosed by the invention is constructed by transfecting P0-generation UCMSC with UCMSC specific LNP and screening a cell subset with low expression of HLA-I, the problems that existing universal cell construction depends on a virus or an electrotransfection system and genome change and immunological rejection exist are solved, and the optimal universal UCMSC has the effects of continuously and stably low immunogenicity, effectively avoiding immunological rejection and being free of permanent genome change. The construction method provided by the invention is safe and reliable, is simple and convenient to operate, improves the clinical accessibility of UCMSC cell therapy, reduces the burden of patients, and has a wide application prospect.

The invention discloses an antibody specifically binding to CD48-1 protein or an antigen binding fragment thereof and application thereof, and belongs to the technical field of biological medicine. The invention further discloses application of the antigen binding fragment specifically binding to the CD48-1 protein, the antibody, polynucleotide, an expression vector, a host cell and the conjugate. The invention also discloses a pharmaceutical composition which comprises one of the antigen binding fragment specifically binding to the CD48-1 protein, an antibody, polynucleotide, an expression vector, a host cell and a conjugate. The antibody or the antigen binding fragment thereof has the beneficial effects that immunological rejection caused by species difference does not exist, and the antibody or the antigen binding fragment thereof has specific binding performance to human CD48-1 full-length protein, can be used for detecting the CD48-1 protein and diagnosing diseases related to the CD48-1 protein, can be used for preparing drugs specifically binding to the CD48-1 protein, and can be used for preparing the CD48-1 protein. The CD48-1 protein related diseases can be treated or prevented, and the CD48-1 protein has a wide application prospect.

The invention relates to a Sebastes schlegeli endogenous retrovirus envelope protein Penv, a lentiviral vector and application thereof, and belongs to the field of genetic breeding of molecular biology, and the amino acid sequence of the envelope protein Penv is as shown in SEQ ID NO.1. The invention further provides an in-vitro assembly system, a transformant and a kit containing membrane fusion protein particles and lentiviral particles of the envelope protein Penv and application of the envelope protein Penv. VSVG protein is replaced with Penv protein from sclerobone fish, so that the transduction efficiency of the lentiviral particles to sclerobone fish cells is effectively improved, and the transduction efficiency of the lentiviral particles to the sclerobone fish cells is improved. And efficient gene delivery is realized. Meanwhile, as the endogenous Env protein, the Env protein overcomes the immunological rejection of a host to the exogenous Env protein, and also has the potential of in-vivo application.

The invention provides an optimized and far potent chimeric antigen receptor for its use in the treatment of HvG disease in a patient having received a transplant, for use in suppressing the host's immune response directed against the transplant. The fusion protein is adapted for use in suppressing the immune rejection of a transplant which contains or expresses HLA-A*02 in a recipient patient who is negative for HLA-A*02, i.e. the patient prior to transplantation does not express HLA-A*02. The fusion protein is a chimeric antigen receptor (CAR), which upon expression in regulatory T-cells (Treg) causes a specific suppressor activity of the regulatory T-cells in the presence of HLA-A*02.

Provided are a universal cell system, a construction method therefor, and use thereof. Universal mesenchymal stem cells are constructed by means of the combination of electroporation and CRISPRoff gene editing, and the cells can survive stably in a pulmonary inflammatory pathological environment to provide sustained treatment, significantly improve multiple indicators of acute pneumonia, solve immune rejection, and provide new cell therapies and ideas for acute pneumonia. CRISPRoff is introduced into universal CTL cells by means of electroporation technology, targeting a specific region and inhibiting the expression of HLA-I in T cells; thus, T cells with low immunogenicity are constructed, and the cells can avoid allogeneic immune rejection. The universal cell system combines the advantages of both transient transfection and CRISPRoff gene editing, has great significance in the field of cell therapy, provides a more comprehensive and effective solution for the treatment of various diseases, and has a wide application prospect.

This invention provides a xenotransplant donor pig that does not express the TEKT5 gene and its preparation method. The TEKT5 gene can cause the risk of xenogeneic immune rejection. The invention also utilizes the CRISPR / Cas9 system to knock out the TEKT5 gene, verifying that the lack of TEKT5 gene expression can effectively reduce the binding ability of donor pig organs, tissues and / or cells to recipient IgG and IgM, improve the ability of donor pig organs, tissues and / or cells to resist recipient complement-mediated cytotoxicity, and prolong the recipient survival time of donor pig organs, tissues and / or pig cells.

To provide genetically engineered stem cells, plasma cells, and B cells for avoiding immune rejection within a host, and methods of making the same and uses thereof.SOLUTION: Provided is a method of differentiating human embryonic stem cells (ES cells) into plasma cells, the method comprising producing precursor cells and differentiating the precursor cells into B cells.SELECTED DRAWING: Figure 10

The invention particularly relates to a sebastes schlegeli endogenous retrovirus envelope protein percomORF, a lentiviral vector and application of the sebastes schlegeli endogenous retrovirus envelope protein percomORF and the lentiviral vector, and belongs to the field of genetic breeding of molecular biology, and the envelope protein percomORF has an amino acid sequence as shown in SEQ ID NO.1. The invention also covers a membrane fusion protein particle constructed based on the protein, a system for in-vitro assembly of lentivirus particles, a corresponding transformant and a matched kit. By replacing conventional VSVG protein with percomORF protein from sclerobone fish, the infection and transduction efficiency of lentivirus on sclerobone fish cells can be effectively enhanced, and more efficient gene delivery is realized. Besides, the protein belongs to host endogenous Env protein and is beneficial to avoiding immunological rejection caused by introduction of foreign protein, so that the protein has good potential in in-vivo gene delivery application.

The present disclosure provides a recombinant humanized collagen VIII, which is a triple helix structure, has good cell adhesion activity, and is applied to human body without immune rejection and allergic reaction.

A recombinant human collagen and a method for building same are provided. The amino acid sequence of the recombinant human collagen is SEQ ID NO. 1: GPAGARGNDGATGAAGPPGPTGPAGPPGFP. The recombinant human collagen does not have a signal peptide and a transmembrane domain and is a novel hydrophilic protein. In addition, the protein does not have an antigenic determinant and does not elicit an immunological rejection response when applied to human body. The present invention further discloses a method for building and synthesizing a low-immunogenic hydrophilic recombinant human collagen. The recombinant human collagen synthesized by using the present invention has high purity, no virus risk, and a high expression level. The protein can be widely applied to related biomedical products, regenerative medicine products, tissue engineering and beauty products, health care products, cosmetic products, among others.

The invention relates to the technical field of biological materials, in particular to chitosan-mussel mucin bionic polypeptide-SVF composite hydrogel as well as a preparation method and application thereof. The mussel mucin bionic polypeptide endows the hydrogel with strong adhesion capacity, so that the hydrogel can be firmly adhered to the surface of cartilage, and SVF loss is prevented; as a carrier of the SVF, the hydrogel can be fixed in an articular cavity, the retention time of the hydrogel is prolonged, and the treatment effect is continuously achieved. Chitosan and mussel mucin bionic polypeptide have good biocompatibility and do not cause immunological rejection, an RGD sequence in the polypeptide can promote cell adhesion, chitosan provides a good cell growth microenvironment, and colonization, survival and function exertion of cells in SVF are facilitated. Chitosan has a certain cartilage repair promoting effect and has a synergistic effect with SVF, cartilage regeneration can be more effectively promoted, a hydrogel precursor solution has good fluidity, the hydrogel precursor solution can be injected into an articular cavity in a minimally invasive mode, and operation is easy and convenient.

The invention discloses an antigen binding fragment capable of specifically binding to NKG2A protein. The invention also discloses an antibody, a polynucleotide, an expression vector and a host cell. The invention also discloses a preparation method of the antibody. The invention also discloses a conjugate. The invention further discloses application of the antigen binding fragment specifically binding to the NKG2A protein, the antibody, polynucleotide, an expression vector, a host cell and the conjugate. The invention also discloses a pharmaceutical composition which comprises one of the antigen binding fragment specifically binding to the NKG2A protein, an antibody, polynucleotide, an expression vector, a host cell and a conjugate. The antibody or the antigen binding fragment thereof has no immunological rejection caused by species difference, and has specific binding performance to human NKG2A full-length membrane protein.

The application discloses a multifunctional artificial organ device, which comprises a shell, a blood pipe bundle and a hydrogel, the blood pipe bundle is contained in a containing cavity, the blood pipe bundle is communicated with a blood inlet and a blood outlet, the hydrogel is filled in the containing cavity, the hydrogel comprises a gel layer and allogeneic therapeutic cells, the allogeneic therapeutic cells are wrapped in the inside of the gel layer, and the allogeneic therapeutic cells absorb nutrient substances and oxygen separated from the blood pipe bundle and secrete therapeutic factors to the blood pipe bundle. The multifunctional artificial organ device in the embodiment of the application wraps the allogeneic therapeutic cells in the inside of the gel layer, so that the immune rejection of the human body is reduced, the human blood is filtered through the blood pipe bundle, the nutrient substances and oxygen are separated from the blood pipe bundle for normal metabolism of the allogeneic therapeutic cells, the allogeneic therapeutic cells generate therapeutic factors, the therapeutic factors flow to internal organs along with the blood, and the purpose of disease treatment is achieved.

The invention discloses application of keratin in preparation of a bone repair material, and relates to the technical field of biomedical engineering. The preparation method comprises the following steps: extracting bone marrow mesenchymal stem cells, and carrying out osteogenic induction culture under the intervention of keratin with the concentration of 100-800 [mu] g / ml; the culture conditions of the BMSCs are as follows: in a constant-temperature incubator with the temperature of 37 DEG C and 5% CO2, a culture medium contains a precooled complete culture medium; the first liquid changing time of the primary culture of the BMSCs is 48-72 hours, then the liquid is changed once every 2-3 days, and passage is carried out when the cell fusion degree reaches 80%-90%. Keratin is adopted as a natural biological material, has good biocompatibility and biodegradability and can well interact with cells, and immunological rejection is reduced.

The application provides a milk exosome coated PLGA nanometer anti-tuberculosis drug system and preparation and application. The system structure is: anti-tuberculosis drug-milk exosome@PLGA-anti-tuberculosis drug. The anti-tuberculosis drug is selected from a combination of one or more of aminoquinolones, benzothiazoles, arylquinolines, nitrobenzamide and benzothiazinone anti-tuberculosis drugs. The nanometer anti-tuberculosis drug system prolongs the circulation time of nanoparticles in blood, improves the bioavailability of the drug, enhances the cell uptake efficiency of nanoparticles, improves the drug delivery effect, reduces the immune rejection reaction and potential toxicity, and improves the safety of treatment.

The present disclosure provides a method for judging the level of immune rejection between heterologous cells, tissues or organs, and relates to the field of biological medicine. The method provided by the present disclosure can quickly and objectively compare the interspecies relative phagocytosis rate of phagocytes in a single experiment, and provides a new way for evaluating and researching the level of immune rejection between heterologous cells, tissues or organs.

The application relates to the field of biomaterials, and particularly discloses a kind of acellular matrix material and a preparation method thereof.The preparation method of the material comprises the following steps: extracting tissue material of a mammal, performing acellular treatment on the tissue material to obtain acellular tissue material, freeze-drying the tissue material, and then crushing the freeze-dried tissue material to obtain animal-derived acellular matrix; the animal-derived acellular matrix is resuspended in water, mixed with a modified epoxidized chitosan solution, and then transglutaminase is added to perform a reaction; the product obtained is freeze-dried to obtain the acellular matrix material.The method can improve the biocompatibility of the acellular matrix and reduce the immune rejection reaction by cross-linking the animal-derived acellular matrix with modified epoxidized chitosan; at the same time, since the cross-linking reaction is a biological cross-linking reaction under the action of transglutaminase, the biological activity factors contained in the acellular matrix are not easily destroyed during the cross-linking process, and the biological activity and safety are better.