29 results about "Furin" patented technology

The invention discloses a reconstructed respiratory syncytial virus F protein trimer, relates to the technical field of genetic engineering vaccines, and designs an RSV F protein trimer, a monomer of the trimer does not contain a p27 sequence, and a furin enzyme digestion peptide fragment aa110-aa136 is deleted; the F2 structural domain and the F1 structural domain are connected through a GS connexon; the invention also designs point mutation combinations, and the point mutation combinations can form an inter-chain disulfide bond, so that covalent connection of the trimer is realized, and the problem of depolymerization of the trimer is fundamentally solved; the trimer is stabilized in a pre-F state, a post-F sample structure does not exist, and an ELISA result shows that a neutralizing epitope is completely reserved; the trimer antigen structure is challenged by adopting a thermal acceleration experiment method, and a result shows that the purity of the trimer antigen reaches 95% or above after the trimer antigen is placed at 37 DEG C for 28 days, and the trimer antigen is very good in stability; when the trimer is used for preparing the vaccine, the standard required by laws and regulations can be met without freeze-drying.

The invention belongs to the technical field of biology, and relates to an RSV pre-F mutant as well as a preparation method and application thereof. Relative to a wild type F0 polypeptide, the RSV pre-F mutant meets the following conditions: (1) the RSV pre-F mutant does not contain a furin enzyme cutting site fragment, a P27 polypeptide, a transmembrane structural domain and an intracellular structural domain; (2) the gene has mutations of S180C, S186C, A170C, V179C, A241C, Q279C, D486C and A490C; and (3) the C end of the F1 polypeptide is not connected or is connected with an aggregation motif. The conformations of the mutant and the trimer thereof are highly stable, the mutant and the trimer thereof can be self-assembled to form the trimer without depending on a heterotrimer structural domain, a high-level binding antibody and a neutralizing antibody can be induced after immunization, and the situation that the high-level binding antibody with non-neutralizing activity is generated when the heterotrimer structural domain is immunized is avoided, so that the quality of the antibody is improved.

The invention belongs to the technical field of biological medicine, and discloses application of a Furin inhibitor in preparation of a medicine for preventing, delaying or treating idiopathic pulmonary fibrosis, the effect of the Furin inhibitor in inhibiting generation of P61-Sema3E so as to delay the idiopathic pulmonary fibrosis is found for the first time, the key effect of Furin and P61-Sema3E in generation and development of IPF is further determined, and the application of the Furin inhibitor in preparation of the medicine for preventing, delaying or treating the idiopathic pulmonary fibrosis is provided for the first time. And a new target can be provided for prevention and treatment of IPF. The invention determines that the Furin inhibitor inhibits activation, proliferation and migration of human primary lung fibroblasts by inhibiting the enzyme activity of Furin, reducing the conversion from P87-Sema3E to P61-Sema3E and reducing the generation of P61-Sema3E, so that a new treatment strategy is provided for IPF.

The invention relates to novel inhibitors of the serine protease furin and related furin-like proprotein convertases according to claim 1 and methods for their synthesis as well as use for the manufacture of medicaments for the treatment of furin-dependent viral and bacterial infectious diseases, as well as other diseases in which furin is involved, such as cystic fibrosis, cancer, osteoarthritis, hypertension, and neurodegenerative diseases.

The present disclosure provides a fluorescence resonance energy transfer (FRET) nanoprobe and a preparation method and use thereof, and belongs to the technical field of targeted nanomaterials. The FRET nanoprobe includes a loading component and an encapsulating component that encapsulates the loading component, where the loading component includes a carrier and DOX coated in the carrier, and the carrier is a carboxyl-modified hollow mesoporous silica nanoparticle (HMSN); and the encapsulating component includes an RVRR peptide and PAMAM / TPE. In the present disclosure, based on condensation properties of a carboxyl group of the carboxyl-modified HMSN, the RVRR peptide and the small-molecule polymer PAMAM / TPE are encapsulated on an outer surface of the HMSN by a reaction of the RVRR peptide that is specifically responsive to Furin and an amino group modified on a surface of the PAMAM / TPE with the carboxyl group on the surface of the HMSN. Therefore, the DOX is effectively encapsulated.

The present invention discloses a recombinant humanized filaggrin and its uses. The recombinant humanized filaggrin contains a humanized LEKTI protein fragment, and the humanized LEKTI protein fragment contains the humanized Kazal motif protein sequence shown in SEQ ID No.2; it also contains a humanized FLG protein fragment, and the humanized FLG protein fragment is linked to the humanized LEKTI protein fragment through a linker containing a furin cleavage site. After cleavage by interstitial furin protease, the two protein fragments perform their respective functions. The recombinant humanized filaggrin of the present invention has the prospect of being developed into a drug, a cosmetic or a medical device for treating diseases that can be treated or alleviated by supplementing FLG and / or inhibiting kallikrein KLK5. Diseases that can be treated or alleviated by supplementing FLG and / or inhibiting KLK5 include atopic dermatitis, Netherton syndrome and tumors with high expression of KLKs.

The application belongs to the technical field of biology and relates to an RSV pre-F mutant, a preparation method and application thereof. Compared with a wild-type F0 polypeptide, the RSV pre-F mutant satisfies the following conditions: (1) does not contain a furin enzyme cutting site fragment, a P27 polypeptide, a transmembrane domain and an intracellular domain; (2) has mutations S180C, S186C, A170C, V179C, A241C, Q279C, D486C and A490C; and (3) the C terminal of an F1 polypeptide is not connected or connected with an aggregation motif. The mutant and a trimeric conformation thereof are both highly stable, can self-assemble into a trimer without a heterologous trimeric domain, can induce high levels of binding antibodies and neutralizing antibodies after immunization, avoid high levels of non-neutralizing active binding antibodies produced when immunization is performed on the heterologous trimeric domain, and thus improve the quality of antibodies.

The application discloses a plant-expressed varicella-zoster virus gB recombinant antigen and a preparation method, product and application thereof, and belongs to the technical field of plant molecular biology and vaccine engineering. The technical problems to be solved are that the existing VZV gB protein has low heterologous expression, poor stability and insufficient antigen activity; the existing VZV vaccine has high production cost, is difficult to popularize and has a single antigen with an immune escape risk; and the plant expression system is not mature in VZV gB antigen production, and lacks a complete preparation scheme and related products. The technical solution is that the natural VZV gB protein is modified, a furin protease cleavage site is knocked out, and a H527P mutation is introduced, related nucleic acid molecules, vectors and plant source cells are constructed, high-activity antigens are obtained through culture and purification, and the high-activity antigens are applied to the preparation of VZV drugs / vaccines, and have the advantages of low cost, high safety and strong immunogenicity.

The invention provides a method for in-vitro expression and purification of recombinant human interleukin 15 in mammalian cells, which comprises the following steps: a, providing a first expression vector comprising nucleic acid encoding a fusion protein of maltose binding protein (MBP) and recombinant human IL-15, the fusion protein comprises the following elements from the 5'end to the 3 'end: 5'-MBP-Furin restriction enzyme cutting site-His tag-enterokinase restriction enzyme cutting site (EK)-rhIL-15-3 '; b, providing a second expression vector, wherein the second expression vector comprises nucleic acid for coding furin; c, co-transfecting the first expression vector and the second expression vector to mammalian cells, and performing fermentation culture to enable the cells to express recombinant human IL-15 protein; d, centrifuging to obtain fermentation supernate from the step c; e, carrying out affinity chromatography through a His tag, so as to obtain a His-EK-rhIL-15 fragment; f, the fragment is subjected to enzyme digestion with enterokinase, affinity purification is conducted again through the His tag, a flow-through substance is collected, and the flow-through substance comprises rhIL-15; and g, purifying the flow-through substance from the step f by anion exchange chromatography to obtain the purified rhIL-15 protein.

The application discloses a reconstructed respiratory syncytial virus F protein trimer, and relates to the technical field of genetic engineering vaccines.The application designs a RSV F protein trimer, the monomer of the trimer does not contain a p27 sequence, and a furin enzyme cleavage peptide segment aa110-aa136 is deleted; a GS linker is used for connecting between an F2 domain and an F1 domain; the application also designs point mutation combinations, the point mutation combinations can form inter-chain disulfide bonds, so that covalent connection of the trimer is realized, and the problem of trimer depolymerization is fundamentally solved; the trimer is stably kept in a pre-F state, and there is no post-F-like structure; an ELISA result shows that neutralizing epitopes are completely retained; a thermal acceleration experiment method is used to challenge the trimer antigen structure, and the result shows that the trimer antigen purity reaches more than 95% after being placed at 37 DEG C for 28 days, and the stability is very good; the trimer is used to prepare a vaccine, and the vaccine can meet the standard of a regulation requirement without freeze drying.

The invention relates to the technical field of medicines, and relates to application of licochalcone B as a Furin enzyme inhibitor. In particular to application of licochalcone B in preparation of drugs for preventing, relieving and / or treating diseases related to Furin enzyme activity increase. The application shows that the licochalcone B has a certain inhibition effect on Furin enzyme activity, has a good pharmacodynamic effect on hypoxia-induced pulmonary arterial hypertension and monocrotaline-induced pulmonary arterial hypertension, can obviously reduce right ventricular systolic pressure, improve right heart remodeling and pulmonary artery blood flow, inhibit pulmonary artery blood vessel remodeling, and can be used for treating pulmonary arterial hypertension. In addition, the Furinase signal channel in the lung tissue of the pulmonary arterial hypertension disease can be obviously reduced. Licochalcone B has good application and development prospects, and is an ideal compound for treating pulmonary arterial hypertension and complications thereof.

Provided are methods for treating viral infections in subject in need thereof. In some embodiments, the method include administering to the subject a composition that has an effective amount of an agent that selectively interferes with host protease function to inhibit fusion-ready viral fragment generation, optionally S2 in case of SARS-CoV2 or GP160 or GP120 in case of HIV, and / or to destabilize a full-length viral fusion protein, optionally SARS-CoV-2 spike. Also provided are compositions that include an effective amount of an agent that selectively interferes with host protease function to inhibit fusion-ready viral fragment generation, optionally S2 in case of SARS-CoV2 or GP160 or GP120 in case of HIV, and / or to destabilize a full-length viral fusion protein, optionally SARS-CoV-2 spike, which compositions can optionally be employed in the disclosed methods.

The invention provides a fusion protein which is characterized in that the fusion protein comprises the following elements from the 5'end to the 3 'end: 5'-MBP-Furin restriction enzyme cutting site-rhIL-7-3 ', and a method for in-vitro expression and purification of recombinant human interleukin 7 in mammalian cells, and the method comprises the following steps: a, providing a first expression vector, the first expression vector comprises nucleic acid for coding the fusion protein; b, providing a second expression vector, wherein the second expression vector comprises nucleic acid for coding furin; c, co-transfecting the first expression vector and the second expression vector to mammalian cells, and performing fermentation culture to enable the cells to express recombinant human IL-7 protein; d, centrifuging to obtain fermentation supernate from the step c; and e, purifying by using POROS XS and CHT chromatographic methods to obtain the rhIL-7 fragment.

The application discloses a combined biomarker combination and evaluation model for evaluating chronic low-grade inflammation of polycystic ovary syndrome, and belongs to the technical field of biomarkers. The combined biomarker combination comprises inflammation-related proteins and metabolites; the inflammation-related proteins comprise FURIN, CCL3, CCL8, CD38, NOS2, NOS3, IL18R1 and HGF; and the metabolites comprise lithocholic acid-3-O-glucuronide and taurine. The application provides a combined biomarker combination for diagnosing and evaluating the chronic inflammation state of polycystic ovary syndrome and an application method thereof. By jointly detecting specific inflammatory proteins and metabolites, the systemic chronic inflammation load of PCOS patients is quantitatively evaluated, and the combined biomarker combination has the beneficial effects of high stability, accurate discrimination, wide applicability and easy clinical transformation, and solves the problem that there is no objective evaluation method for the chronic inflammation state of PCOS.

The present invention discloses TH17 CD4+ T cell subsets in bladder cancer, their characteristic genes and applications, relating to the technical field of biomedicine. A biomarker group for identifying, detecting or assaying TH17 CD4+ T cells according to the present invention, the biomarker group includes at least one of the genes IL17A, FURIN, CTSH, KLRB1, or a protein or protein fragment encoded by the gene. The characteristic genes IL17A, FURIN, CTSH, KLRB1 screened by the present invention are lowly expressed in TH17 CD4+ T cells in bladder cancer tissues and can be used for tumor auxiliary diagnosis, prognosis judgment, and preparation of drugs for immunotherapy; the expression of the characteristic genes of the present invention in TH17 CD4+ T cells in normal bladder tissues is higher than that in bladder cancer tissues, indicating that the characteristic genes of the present invention can promote the immune function of TH17 CD4+ T and can be used for the preparation of drugs for treating bladder cancer.

The present invention discloses a novel recombinant polypeptide, and methods for stimulating protective or therapeutic immune responses to human herpesvirus. The invention relates to a composition comprising isolated homotrimers of a modified gB polypeptide from human cytomegalovirus (hCMV), wherein the gB polypeptide comprises an immunoglobulin signal peptide, an ex-tracellular domain with furin cleavage site mutations, and / or the intravirion domain, but lacks the transmembrane domain. Also the use thereof and methods of treating and preventing CMV associated disease or CMV infections with said composition.

The present results show for the first time that the HLA proteins HLA-H and HLA-J are specifically expressed at the surface of breast tumor cells (in particular Triple Negative Breast Cancer) and can therefore serve as specific targets for various immunotherapeutic agents, preferably CAR-expressing macrophages. The present invention therefore provides new immunotherapeutic molecules recognizing peptides that are specifically present in the HLA protein HLA-H or in the HLA protein HLA-J at the surface of breast cancer cells, nucleic acids encoding said molecules, immune cells expressing said molecules, as well as therapeutical uses and / or treatment methods involving them, for alleviating the symptoms of patients suffering from breast cancer, in particular from Triple Negative Breast Cancer. The invention specifically proposes to use furin-inhibited CAR-macrophages targeting extracellular peptides of the HLA-H or HLA-J proteins for treating patients suffering from breast cancer, in particular from Triple Negative Breast Cancer.

Immunogenic fusion proteins against infectious animal diseases caused by feline coronavirus (FCoV). A fusion protein is disclosed, which comprises a CD40-binding domain; an antigen of FCoV; a translocation domain located between the CD40-binding domain and the antigen, and a furin and / or cathepsin L cleavage site located between the CD40-binding domain and the translocation domain. Also disclosed are pharmaceutical compositions, expression vectors and use of the fusion proteins of the invention for eliciting an antigen-specific cell-mediated immune response, or for reducing, inhibiting, treating and / or ameliorating an animal disease caused by FCoV infection.

The present invention provides a linear antigen peptide for diagnosing schizophrenia and its application, a kit and its application, and relates to the field of schizophrenia diagnosis. The linear antigen peptide is used to bind to a schizophrenia diagnostic marker, and the amino acid sequence of the linear antigen peptide includes at least one of SEQ ID NO. 1 to 5. The technical solution of the present invention detects the proportion of antibodies corresponding to the antigens in the sample by using at least one peptide segment containing FURIN antigen, MOB4 antigen, PDIA3 antigen, MAD1L1 antigen and CACNA1C antigen to diagnose schizophrenia. Compared with the normal person, the expression content is low, which means that it meets the diagnosis of schizophrenia.

The present invention discloses a recombinant humanized collagen and uses thereof, the recombinant humanized collagen contains a humanized LEKTI protein fragment and a type III human collagen fragment, and the two protein fragments are connected through a linker containing a furin enzyme cutting site. After the recombinant humanized collagen is cut by the furin protease, two protein fragments are generated and exert respective functions. The recombinant humanized collagen has the prospect of being developed into medicines, cosmetics or medical instruments for treating diseases which are treated or relieved by supplementing III-type human collagen fragments and / or inhibiting kallikrein KLKs; diseases treated or relieved by supplementing the III-type human collagen fragment and / or inhibiting the KLKs include atopic dermatitis, internal sephton syndrome and tumors with high expression of the KLKs.

Fusion proteins for immunotherapy against cancer and infectious diseases are disclosed. A fusion protein according to the invention comprises a CD40-binding domain; an antigen; and a translocation domain located between the CD40-binding domain and the antigen, in which a furin and / or cathepsin L cleavage site is present in the fusion protein between the CD40-binding domain and the translocation domain. The antigen is an antigen of a pathogen or a tumor antigen. The furin and / or cathepsin L cleavage site permits removal of the CD40-binding domain away from the fusion protein via furin and / or cathepsin L cleavage. Also disclosed are pharmaceutical compositions, expression vectors and use of the fusion proteins of the invention for eliciting an antigen-specific cell-mediated immune response, treating a tumor and / or a disease caused by a pathogen in a subject in need thereof.

The invention relates to the technical field of biological medicine, and discloses an active EDA-A1 loaded engineered small extracellular vesicle and a preparation method thereof, the preparation method comprises the following steps: step 1) overexpressing EDA-A1 protein on epidermal stem cells in a lentivirus infection mode, and screening to obtain stably transfected strain cells stably overexpressing EDA-A1; 2) performing multiplication culture on the stably transfected strain cells, and adding a Furin protease inhibitor in the culture process; 3) after the multiplication culture is completed, collecting cell culture supernatant and extracting small extracellular vesicles to obtain engineered EDA-A1 small extracellular vesicles carrying EDA-A1 active fragments; compared with the EDA-A1 recombinant protein, the engineered small extracellular vesicles prepared by the preparation method provided by the invention have the advantages of being easy to obtain, capable of exerting the functions of the EDA-A1 protein, stable in property, not easy to degrade and the like, and have a relatively great application prospect in clinical treatment of diseases related to ectoderm dysplasia in the future.

The present disclosure provides a recombinant Hepatitis C Virus glycoprotein comprising a heterodimer of E1 and E2 glycoproteins bearing at least 60% homology to SEQ ID No. 1, an engineered furin cleavage site and a hydrophilic amino acid linker, wherein the E1 and E2 glycoproteins partially or completely lack their respective transmembrane domain(s). Further provided herein are nucleic acid(s) encoding the said recombinant Hepatitis C Virus glycoprotein, nanoparticle conjugate(s) comprising the said recombinant Hepatitis C Virus glycoprotein and compositions comprising the recombinant Hepatitis C Virus glycoprotein, the said nucleic acid(s) or the nanoparticle conjugate(s). Also envisaged herein are applications of the recombinant Hepatitis C Virus glycoprotein or the composition comprising the same.

The present invention relates to the field of biomedicine. The present invention provides the application of mammalian MARCH proteins in anti-virus and anti-tumor, wherein human MARCH1 and MARCH2 proteins, bovine MARCH1 and MARCH2 proteins and mouse MARCH2 proteins can significantly block the cleavage and transport of viral membrane proteins, inhibit the activity of Furin protease, and block the replication of cancer cells; it provides valuable reference for subsequent anti-virus and anti-cancer research, and may promote the research and development of new anti-enveloped virus infection and cancer treatment strategies.

The invention discloses a recombinant humanized sericin and application thereof. The recombinant humanized sericin contains a humanized LEKTI protein fragment, and the humanized LEKTI protein fragment contains a humanized Kazal motif protein sequence as shown in SEQ ID No.2; the humanized LEKTI protein fragment is characterized by further containing a humanized FLG protein fragment, and the humanized FLG protein fragment is connected with the humanized LEKTI protein fragment through a linker containing a furin restriction enzyme cutting site. After the recombinant humanized silk protein is cut by intercellular gap furin protease, the two protein fragments perform respective functions. The recombinant humanized silk protein has the prospect of being developed into medicines, cosmetics or medical instruments for treating diseases treated or relieved by supplementing FLG and / or inhibiting kallikrein KLK5, and the diseases treated or relieved by supplementing FLG and / or inhibiting KLK5 comprise atopic dermatitis, internal sephton syndrome and tumors with high KLKs expression.

The present invention provides a method for providing a prognosis for a subject with lung cancer, the method comprising: (a) contacting a biological sample from the subject with reagents that specifically bind to each member of a panel of biomarkers comprising ANLN, ASPM, CDCA4, ERRFI1, FURIN, GOLGA8A, ITGA6, JAG1, LRP12, MAFF, MRPS17, PLK1, PNP, PPP1 R13L, PRKCA, PTTG1, PYGB, RPP25, SCPEP1, SLC46A3, SNX7, TPBG, XBP1; (b) determining a riskscore of the subject based on the nucleic acid levels of expression of the biomarkers in the samples; and (c) providing a prognosis for the lung cancer based on the risk score of the subject.

This invention relates to Furin / hydroxyl radical dual-responsive size-changing nanoparticles, their preparation, and applications. The Furin / hydroxyl radical dual-responsive size-changing nanoparticles use an AIE photosensitizer as the core and DSPE-PEG as the substrate. 2K MAL nanoparticles serve as carriers, with functional peptides coupled to their surfaces via Michael addition reactions. The core functional building block is a self-designed and custom-synthesized R1 peptide, which possesses a triple function: high specificity recognition by Furin protease, OH-responsive tyrosine oxidation cross-linking, and coupling with DSPE-PEG nanoparticles. Its simple sequence significantly enhances tumor selectivity. The peptide is covalently modified with natural peptides using a nanoprecipitation method, avoiding complex chemical modifications and exogenous orthogonal biological groups, thus mitigating the toxicity and synthesis costs of traditional systems. Under the dual conditions of Furin protease overexpression and the presence of OH, size transformation is triggered, enabling deep tumor penetration with small sizes and long-term intratumoral retention through in-situ large-size assembly, demonstrating clinical translational potential.

1.The name of the design product: ornament (Fulu Ruyi). 2.The use of the design product: for ornaments and decoration. 3.The design points of the design product: in shape. 4.The picture or photo that best shows the design points: perspective view 1. 5.The design points of the left and right views have been embodied in perspective view 1-perspective view 4, and the left and right views are omitted.