219 results about "Immune rejection" patented technology

The invention provides a recombinant XVII type collagen and application thereof, and relates to the technical field of protein engineering. The novel recombinant human XVII type collagen is obtained by optimizing and screening collagen structural domain sequences of the human XVII type collagen and then combining the sequences. The recombinant human XVII type collagen is consistent with the corresponding part of the amino acid sequence of the human XVII type collagen, does not generate immunological rejection when being applied to a human body, and can be widely applied to the industries of surgical medical treatment and medical beauty. In addition, the recombinant human XVII type collagen is high in stability, and the problem of protein degradation in the process of expressing recombinant protein by pichia pastoris can be avoided. In addition, the recombinant human XVII type collagen also has the effects of high biological activity, high biological safety, promotion of cell proliferation and differentiation and promotion of hair growth, and can be applied to the field of cosmetics or medicines as a functional component.

The invention provides recombinant VIII type humanized collagen and application thereof, and the recombinant VIII type humanized collagen is of a triple helix structure, has good cell adhesion activity, does not generate immunological rejection and anaphylactic reaction when being applied to a human body, is a brand new human body synthetic biological material, and has good application prospects.

The invention provides a micromolecular recombinant XVII type collagen as well as a preparation method and application thereof, and relates to the technical field of protein engineering. The novel recombinant human XVII type collagen is obtained by optimizing and screening a plurality of spiral region sequences such as a collagen structural domain, a C-terminal region and a middle region of the human XVII type collagen. The amino acid composition of the recombinant XVII type collagen is consistent with that of a natural collagen alpha1 chain, immunological rejection is not generated when the recombinant XVII type collagen is applied to a human body, the recombinant XVII type collagen can be widely applied to surgical medical treatment and medical beauty industries, the molecular weight of the collagen is small, efficient secretion soluble expression in eukaryotic host cells such as pichia pastoris can be achieved, and the recombinant XVII type collagen has a good application prospect. And industrial large-scale production is carried out. According to the present invention, the verification results show that the micromolecular recombinant XVII type collagen further has basement membrane anti-aging activity, wherein the basement membrane anti-aging activity specifically comprises the improvement of the expression levels of the IV type collagen, the VII type collagen and the XVII type collagen;

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.

The invention discloses an engineered autologous tumor tissue scaffold and application thereof, and the engineered autologous tumor tissue scaffold is prepared by performing specific treatment on autologous tumor tissue to induce immunogenic cell death of the tumor tissue, and then sequentially performing freezing and drying steps; the engineered autologous tumor tissue scaffold can be used for loading dendritic cells and constructing personalized tumor vaccines. According to the stent, autologous tumor tissue is adopted, so that a specific and comprehensive tumor antigen pedigree is reserved, and multi-epitope immunostimulation is provided; and meanwhile, excellent biocompatibility is ensured, the immunological rejection risk is reduced, and relatively high safety is ensured.

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.

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 present disclosure features allogeneic modified cells (e.g., T- or NK-cells) having increased persistence, increased resistance to immune rejection, and / or decreased risk of eliciting a host-versus-graft reaction, or a combination thereof. Methods for producing and using the same are also provided.

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 present invention relates to a novel anti-CD40 antibody and use thereof and, more specifically, to a novel anti-CD40 antibody and use thereof, wherein the antibody comprises a complementarity determining region of a specific sequence and exhibits an excellent antagonistic effect by blocking CD40-CD40L signaling. The novel anti-CD40 antibody of the present invention exhibits an excellent antagonistic effect by blocking CD40-CD40L signaling, and thus can be widely used as a preparation for preventing or treating various diseases, such as autoimmune diseases and chronic inflammatory diseases, and as a preparation for inhibiting immune rejection at the time of transplantation.

The invention discloses a composite bone graft material based on bletilla striata polysaccharide and autologous tooth bone meal as well as a preparation method and application of the composite bone graft material. The preparation method comprises the following steps: preparing bletilla striata polysaccharide, namely BSP, from bletilla striata; the method comprises the following steps: pretreating extracted teeth, and crushing to obtain autologous tooth bone powder, namely AutoBT; dissolving the BSP in water, and uniformly stirring to obtain a BSP solution; the AutoBT is poured into the BSP solution, and after standing and stirring, an AutoBT solution loaded with BSP is obtained; and carrying out vacuum drying on the AutoBT solution loaded with the BSP, and carrying out ultraviolet sterilization to obtain the composite bone graft material. The material can be applied to repairing of oral cavity bone defects, bletilla striata polysaccharide has the effects of resisting inflammation, inhibiting bacteria, promoting osteogenesis and inhibiting osteoclast, the bone steady state unbalance state in the periodontitis environment is effectively reversed, meanwhile, autologous tooth bone powder accelerates bone tissue regeneration and integration by means of the natural bionic structure and high porosity of the autologous tooth bone powder, and the bone tissue regeneration effect is improved. The risks of postoperative infection and immunological rejection are reduced.

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 an implantable acellular matrix material and a preparation method thereof, and belongs to the field of biomedical materials. According to the method, natural animal tissues (such as pericardium, achilles tendon or small intestine submucosa) are used as raw materials, a low-temperature chemical combined decellularization treatment technology is adopted, and the method comprises the multi-step synergistic process of pre-cooling soaking balancing, low-temperature enzymolysis, low-concentration surfactant gradient permeation cleaning, low-temperature nuclease degradation, non-crosslinking sterilization and the like. Under the condition that the treatment temperature is strictly kept at 0-8 DEG C, cell components and genetic materials (the residual DNA content is 1t, and the dry weight is 8 ng / mg) are efficiently removed, and meanwhile the natural three-dimensional fine structure of an extracellular matrix (ECM), the integrity of collagen fibrils and key bioactive components (such as glycosaminoglycans (GAGs)) are reserved to the maximum extent. The host immunological rejection reaction of the obtained material is remarkably reduced, host cell ingrowth, vascularization and tissue function reconstruction can be effectively promoted after implantation, and the material is suitable for high-end implantation scenes such as soft tissue repair and regenerative medical stents.

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 spot universal CFR64-T cell prepared on the basis of CRISPR / Cas9 as well as a preparation method and application thereof. The CFR64-T cell is obtained by induced differentiation of recombinant human embryonic stem cells; in the recombinant human embryonic stem cell, a coding sequence of a CFR64 molecule is knocked into a TRAC site of the human embryonic stem cell at a fixed point through a CRISPR / Cas9 editing system; the CFR64 molecule comprises an antigen binding structural domain, a transmembrane structural domain and an intracellular costimulatory signal structural domain, the antigen binding domain is a human Fc gamma receptor extracellular domain, and the amino acid sequence of the antigen binding domain is shown in SEQ ID NO: 1. The CRISPR / Cas9 technology is adopted, gene integration sites are controllable and free of oncogene mutation risks, TCR genes are knocked out, the immunological rejection risk of universal CFR64-T cells to hosts is reduced, and meanwhile gene expression is more stable.

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.