51 results about "Virus Envelope Proteins" patented technology

This disclosure relates to a recombinant adenovirus comprising a polynucleotide encoding DENV envelope protein and a polynucleotide encoding ferritin heavy chain protein, and uses thereof. This disclosure also provides a recombinant adenovirus comprising a polynucleotide encoding DENV (Dengue Virus) envelope protein and a polynucleotide encoding ferritin heavy chain protein, and a vaccine composition for preventing DENV infection comprising the recombinant adenovirus as an effective ingredient.

The invention discloses a chikungunya virus envelope E2 protein monoclonal antibody and application thereof, and belongs to the technical field of medicines. The chikungunya virus envelope protein E2 expressed by human embryo kidney 293 cells is used as an antigen to immunize a rabbit, B cells capable of being specifically combined with the chikungunya virus envelope protein E2 are screened from rabbit spleen cells through flow sorting, and signal peptide and variable region gene fragments of an antibody are cloned through reverse transcription-polymerase chain reaction. According to the present invention, the chikungunya virus-resistant monoclonal antibody with high neutralizing activity and capable of 100% protection of mice against chikungunya virus lethal attack is obtained by carrying out enzyme-linked immunosorbent assay, in-vitro virus neutralization and mouse toxicity attack experiment after mammalian cell expression and purification, and the recombinant chikungunya virus-resistant monoclonal antibody has characteristics of high neutralizing activity and high immunogenicity, and can be used for preparing the chikungunya virus-resistant monoclonal antibody, and the recombinant chikungunya virus-resistant monoclonal antibody. The monoclonal antibody has application value in prevention and treatment of yellow fever.

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 discloses application of PD-L1 as a drug target for resisting pseudorabies virus infection, the invention discloses PD-L1 as a key host limiting factor for pseudorabies virus infection for the first time, and knockout of PD-L1 can significantly promote replication of pseudorabies virus and induce apoptosis and inflammatory response of host cells. And PD-L1 overexpression can effectively inhibit proliferation of the pseudorabies virus and induce apoptosis and inflammatory response of host cells. Mechanism research results show that PD-L1 can be combined with envelope proteins gB and gD of the pseudorabies virus, and the effect of resisting pseudorabies virus infection is achieved through a cGAS-STNG-IFN pathway. The further research finds that the 125th arginine (ARG125) and the 271th lysine (LYS271) of the PD-L1 protein play a key role in the anti-pseudorabies virus infection effect of the PD-L1. The invention provides a new target spot for drugs for preventing or treating pseudorabies virus infection, and has a good application prospect in the aspect of resisting pseudorabies virus.

Provided is a viral vector having a lipid bilayer envelope, the lipid bilayer envelope comprising an antibody binding domain displayed outside the envelope, the antibody binding domain being cell type specific; a viral envelope protein exhibited outside the envelope, the viral envelope protein being capable of promoting infection of the same cell type; and a nucleic acid molecule comprising a promoter capable of being expressed in the same cell type. Methods of making the viral vectors and methods of modifying cells and treating diseases / conditions using the viral vectors are also provided.

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.

Disclosed herein are compositions and methods for determining the structure of a membrane protein. An epitope from a membrane-proximal external region (MPER) from a viral envelope protein can be grafted on to a variety of diverse membrane proteins to allow for binding structurally characterized antibody fragments, which can aid structural studies.

The invention relates to the technical field of biological medicine, and discloses a lentiviral vector for specifically targeting a target cell and a construction method and application thereof, the lentiviral vector comprises: (1) an antigen targeting artificial protein receptor, the receptor comprising a target cell surface antigen binding domain and a transmembrane domain; (2) a mutated Moreton vesicular disease virus envelope protein; and (3) an expression cassette, wherein the expression cassette comprises a heterologous transgene. The novel lentiviral vector based on the mutated Moreton vesicular disease virus envelope, provided by the invention, can realize specific infection on target cells in vitro and in vivo, and compared with a vesicular stomatitis virus envelope VSV-G, the lentiviral vector constructed based on mutated Moreton vesicular disease virus envelope protein is better in stability in serum, and has a good application prospect. The efficiency of specifically infecting target cells is higher, and the drug effect in a mouse tumor model is more prominent.

The invention discloses an eluent for improving the anion exchange chromatography recovery rate of lentivirus and application of the eluent. The eluent is prepared from a basic buffer solution, 50 to 500 mM of NaCl and 0.2 to 2 M of L-arginine; the pH (Potential of Hydrogen) value of the eluent is 6.5 to 8.0. In order to solve the problems that in the prior art, high-salt elution is adopted, so that the lentivirus activity damage is large, and the recovery rate is low, the concentration of a main elution component NaCl in an eluent is reduced, then the main elution component NaCl is compounded with L-arginine, the lentivirus can be effectively eluted, meanwhile, the damage of a high-salt environment to a virus envelope structure is avoided, and the yield of the lentivirus is improved. And the elution efficiency is improved by utilizing the characteristic that L-arginine inhibits protein interaction. When the eluent is used for chromatographic purification, the recovery rate and activity of the lentivirus can be remarkably improved, impurities such as host cell protein and the like are effectively removed, and a key purification solution is provided for preparing a high-purity and high-activity lentiviral vector for gene therapy.

The invention relates to the technical field of traditional Chinese medicine extract fermentation, and provides a microspore ganoderma lucidum immune protein and herba houttuyniae fermentation method for treating AIDS and application of microspore ganoderma lucidum immune protein and herba houttuyniae fermentation method.The microspore ganoderma lucidum immune protein and herba houttuyniae fermentation method comprises the steps that microspore ganoderma lucidum strains and herba houttuyniae fermentation liquor are co-fermented, beta-cyclodextrin-selenocystine of a specially-made additive is combined, and the microspore ganoderma lucidum immune protein is obtained; the problems that in traditional AIDS treatment, latent infection cells are difficult to remove, toxic and side effects of drugs are remarkable, and the reconstruction efficiency of an immune system is low are effectively solved, experiments prove that the fermentation product can activate the immune system, the cell number and the dendritic cell maturity are remarkably improved, and the curative effect is good. Meanwhile, the multi-target antiviral effect is achieved by blocking virus envelope combination, inhibiting reverse transcriptase activity and inducing latent infection cell apoptosis; the anti-oxidation and anti-inflammatory characteristics can reduce the risk of opportunistic infection, reduce the toxic damage of antiviral drugs to liver, kidney and intestinal tracts, and provide a new scheme for comprehensive treatment of AIDS and nutrition support of patients.

The invention discloses a chikungunya virus monoclonal antibody and application thereof in preparation of preventive and therapeutic antibody drugs, and belongs to the technical field of medicines. The chikungunya virus envelope protein E2 expressed by human embryo kidney 293 cells is used as an antigen to immunize a rabbit, B cells capable of being specifically combined with the chikungunya virus envelope protein E2 are screened from rabbit spleen cells through flow sorting, and signal peptide and variable region gene fragments of an antibody are cloned through reverse transcription-polymerase chain reaction. According to the present invention, the chikungunya virus-resistant monoclonal antibody with high neutralizing activity and capable of 100% protection of mice against chikungunya virus lethal attack is obtained by carrying out enzyme-linked immunosorbent assay, in-vitro virus neutralization and mouse toxicity attack experiment after mammalian cell expression and purification, and the recombinant chikungunya virus-resistant monoclonal antibody has characteristics of high neutralizing activity and high immunogenicity, and can be used for preparing the chikungunya virus-resistant monoclonal antibody, and the recombinant chikungunya virus-resistant monoclonal antibody. The monoclonal antibody has application value in prevention and treatment of yellow fever.

The application provides a virus envelope chimeric receptor and related biomaterials and applications thereof, and belongs to the technical field of molecular biology. Specifically disclosed is a virus envelope chimeric receptor, which comprises, in sequence, an antibody or antigen-binding fragment thereof, a hinge region, a transmembrane region and an intracellular region; the hinge region is selected from a hinge region composed of a hinge region of a CD8 molecule and a hinge region of a vesicular stomatitis virus envelope glycoprotein; the transmembrane region of the virus envelope chimeric receptor is selected from a transmembrane region of the vesicular stomatitis virus envelope glycoprotein; and the intracellular region of the virus envelope chimeric receptor is selected from an intracellular region of the vesicular stomatitis virus envelope glycoprotein. The virus envelope chimeric receptor is used for virus targeting, can improve the infection ability of viruses, reduces the infection rate of viruses on non-T cells to less than 5%, provides a safety guarantee for in-vivo CAR-T preparation, and can be used for industrial production.

Disclosed herein are compositions of retroviruses and methods of using the same for gene delivery, wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.

The present disclosure relates to a novel vaccine strategy against hepatitis B virus (HBV) infection, which is a major cause of chronic liver disease and hepatocellular carcinoma worldwide. The disclosure provides fusion proteins that target dendritic cells (DCs), the key antigen-presenting cells of the immune system, and deliver HBV-derived peptides to both the major histocompatibility complex (MHC) class I and II pathways, thereby inducing strong and specific humoral and cellular immune responses against the viral envelope and core antigens. The disclosure also provides methods of using the fusion proteins for the prevention or treatment of HBV infection and its complications. The inventors have demonstrated in a mouse model that the DC-targeting HBV vaccine candidates can elicit robust antibody and T cell responses, which are essential for the clearance of the virus and the protection from chronic infection.

A viral vector having a lipid bilayer envelope is provided, comprising a cell-type specific antibody-binding domain presented outside the envelope, a viral envelope protein presented outside the envelope capable of promoting infection of the same cell type, and a nucleic acid molecule containing a promoter expressible in the same cell type. Furthermore, a method for producing the viral vector and a method for modifying cells and treating diseases / conditions using this viral vector are also provided.

The invention belongs to the technical field of viral vector design, and discloses a structural prediction-based viral vector targeting optimization method and system.The method comprises the following steps: firstly, obtaining structural information of a target receptor and candidate viral envelope protein; inputting structure information of a target receptor into a trained deep learning structure prediction model, outputting a glycosylation shielding field associated with three-dimensional space coordinates, and quantizing reduction of space accessibility caused by glycosylation by numerical values of the glycosylation shielding field; then docking the candidate virus envelope protein with a target receptor structure, and predicting a candidate binding interface and a corresponding space coordinate set; extracting numerical values from the shielding field based on the coordinate set, and obtaining a shielding punishment score through predefined mathematical operation; constructing a multi-objective optimization function with other optimization objectives; and finally, iterating or screening candidate virus envelope proteins by using an optimization algorithm, and optimizing a function output result. According to the invention, the targeting of the virus vector to target cells can be improved, and the off-target risk is reduced.

The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises: (i) a mitogenic T-cell activating transmembrane protein which comprises a mitogenic domain and a transmembrane domain; and / or (ii) a cytokine-based T-cell activating transmembrane protein which comprises a cytokine domain and a transmembrane domain, wherein the mitogenic or cytokine-based T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells of Natural Killer cells are transduced by such a viral vector, they are simultaneously activated by the mitogenic T-cell activating transmembrane protein and / or the cytokine-based T-cell activating transmembrane protein.

The invention relates to the technical field of biological medicine, and discloses a lentiviral vector and a construction method and application thereof, the lentiviral vector comprises: (1) an antigen-targeted artificial protein receptor, the receptor comprising a target cell surface antigen binding domain and a transmembrane domain; (2) a mutated Maraba virus envelope protein; and (3) an expression cassette, wherein the expression cassette comprises a heterologous transgene. The novel lentiviral vector based on the mutated Maraba virus envelope provided by the invention can realize specific infection on target cells in vitro and in vivo, and compared with a vesicular stomatitis virus envelope VSV-G, the lentiviral vector constructed on the basis of the mutated Maraba virus envelope protein has better stability in serum, and can be used for preparing a novel lentiviral vector of the mutated Maraba virus envelope. The efficiency of specifically infecting target cells is higher, and the drug effect in a mouse tumor model is more prominent.

Provided are a targeting vector and a method for targeting same to a host cell. The vector comprises a first molecule that binds to an endocytosis receptor of the target cell and a second molecule that promotes the release of a substance carried by the targeting vector into a cytoplasm. When the targeting vector is a viral vector, the first molecule is not part of a viral envelope protein, and the second molecule promotes endosomal escape or lysosomal escape of the targeting vector. The first molecule is designed according to the endocytosis receptor of the cell to be targeted, different types of cells can be targeted, and after a reasonable mutation is carried out on the vector, infection of cells that do not need to be targeted can be avoided, thereby improving the accuracy of the vector.

The application discloses a CD7 and CD3 double-targeting fusion protein and application thereof. Specifically, the application discloses an isolated fusion protein, which comprises, from N-terminal to C-terminal, (a) an anti-CD7 single-domain antibody (CD7 VHH); (b) an anti-CD3 single-domain antibody (CD3 VHH); and (c) a transmembrane region, which is used for anchoring the fusion protein on a cell membrane or a viral envelope. And a T cell-targeting pseudotyped lentiviral vector based on the fusion protein is constructed. The pseudotyped lentiviral vector of the application can effectively target and activate T cells, and can deliver the expression CAR-containing vector into T cells, thereby effectively activating T cells and enhancing the target killing ability of T cells.

The present application relates to the technical field of stem cells, in particular to a lentivirus envelope plasmid combination and application thereof, a lentivirus and a packaging method and a method for transducing hematopoietic stem cells. The present application provides an envelope plasmid combination for lentivirus packaging, which is composed of lentivirus packaging plasmids containing VSVG glycoprotein and lentivirus packaging plasmids containing BaEV glycoprotein in a ratio of 3:7; further provided is a method for transducing hematopoietic stem cells with lentivirus, which is simple to operate, can maintain the long-term stemness of hematopoietic stem cells in vitro, can realize efficient and stable transduction of hematopoietic stem cells, and the transduction rate is greater than 90%. The hematopoietic stem cells transduced by the lentivirus transduction method of the present application can be used for hematopoietic stem cell gene therapy of hematopoietic system genetic diseases, such as severe combined immunodeficiency, beta-thalassemia and sickle cell disease, Wiskott-Aldrich syndrome, and has a good application prospect.

To provide retroviral and lentiviral vectors.SOLUTION: The invention provides a retroviral or lentiviral vector having a viral envelope comprising: (i) a mitogenic T cell activating transmembrane protein comprising a mitogenic domain and a transmembrane domain; and / or (ii) a cytokine-based T cell activating transmembrane protein comprising a cytokine domain and a transmembrane domain, wherein the mitogenic or cytokine-based T cell activating transmembrane protein is not part of the viral envelope glycoprotein. When cells such as natural killer cells are transduced with such viral vectors, they are simultaneously activated by the mitogenic T cell activating transmembrane protein and / or the cytokine-based T cell activating transmembrane protein.SELECTED DRAWING: None

The invention discloses a chikungunya virus envelope E2 protein monoclonal antibody and application of the chikungunya virus envelope E2 protein monoclonal antibody in preparation of preventive and therapeutic antibody drugs, and belongs to the technical field of medicines. The chikungunya virus envelope protein E2 expressed by human embryo kidney 293 cells is used as an antigen to immunize a rabbit, B cells capable of being specifically combined with the chikungunya virus envelope protein E2 are screened from rabbit spleen cells through flow sorting, and signal peptide and variable region gene fragments of an antibody are cloned through reverse transcription-polymerase chain reaction. According to the present invention, the chikungunya virus-resistant monoclonal antibody with high neutralizing activity and capable of 100% protection of mice against chikungunya virus lethal attack is obtained by carrying out enzyme-linked immunosorbent assay, in-vitro virus neutralization and mouse toxicity attack experiment after mammalian cell expression and purification, and the recombinant chikungunya virus-resistant monoclonal antibody has characteristics of high neutralizing activity and high immunogenicity, and can be used for preparing the chikungunya virus-resistant monoclonal antibody, and the recombinant chikungunya virus-resistant monoclonal antibody. The monoclonal antibody has application value in prevention and treatment of yellow fever.

The present application relates to a kind of Sebastes schlegelii endogenous retrovirus envelope protein P_env, lentivirus vector and its application, belong to the genetic breeding field of molecular biology, the amino acid sequence of the envelope protein P_env is as shown in SEQ ID NO.1.The present application simultaneously provides the membrane fusion protein plasmid of containing the envelope protein P_env, the in vitro assembly system of lentivirus particle, transformant and kit, and the application of the envelope protein P_env, the P_env protein of the present application is replaced VSVG protein using hard fish source, will effectively improve the transduction efficiency of lentivirus particle to hard fish cell, realize efficient gene delivery.Meanwhile, as endogenous Env protein, overcome the immune rejection of host to exogenous Env protein, also have the potential of in-vivo application.

Provided is a pseudotyped viral particle, a viral envelope surface thereof comprising immune cell-targeting molecules and / or immune cell-activating molecules. Corresponding targeting molecules are designed on the basis of cell receptors to be targeted, enabling targeting of different types of cells. The application scope is broad, including but not limited to the rapid preparation of CAR-T, CAR-NK, and other immunotherapeutic cells in vitro without the need for sorting and activation, as well as the direct generation of CAR-T, CAR-NK, and other immunotherapeutic cells in vivo.

A Dengue virus Envelope Dimer Epitope (EDE) wherein the EDE: c) spans the polypeptides of a Dengue virus Envelope polypeptide dimer; and / or d) is presented on a dimer of Envelope proteins; and / or c) is formed from consecutive or nonconsecutive residues of the envelope polypeptide dimer, wherein the dimer is a homodimer or heterodimer of native and / or mutant envelope polypeptides, from any one or two of DENV-1, DENV-2, DENV-3 and DENV-4. The EDE may be a stabilized recombinant dengue virus envelope glycoprotein E ectodomain (sE) dimer, wherein the dimer is: covalently stabilized with at least one disulphide inter-chain bond between the two sE monomers, and / or covalently stabilized with at least one sulfhydrylreactive crosslinker between the two sE monomers, and / or covalently stabilized by linking the two sE monomers through modified sugars; and / or, covalently stabilised by being formed as a single polypeptide chain, optionally with a linker region, optionally a Glycine Serine rich linker region, separating the sE sequences, and / or non-covalently stabilized by substituting at least one amino acid residue in the amino acid sequence of at least one sE monomer with at least one bulky side chain amino acid, at the dimer interface or in domain 1 (D1) / domain 3 (D3) linker of each monomer. A compound, for example an antibody or antibody fragment that can neutralize more than one Dengue virus serotype, for example an antibody that can bind to an EDE of the invention.

Provided herein are lipid particles containing at least two attachment proteins derived from a paramyxovirus envelope attachment protein and at least one paramyxovirus fusion (F) protein. Also provided are lipid particles, such as lentiviral vectors or lentivirus-like particles, as viral vectors. Also provided are producer cells and compositions containing such lipid particles as well as methods of making and using the lipid particles.

This application provides novel viral envelope glycoproteins for pseudotyping viral vectors, novel designs of synthetic antigen receptors (SARs), novel signaling chains for constructing SARs, novel antigen-binding domains, and novel methods for producing SAR-expressing cells. These novel methods and compositions are widely used in cell therapy.

This invention specifically relates to an endogenous retroviral envelope protein T_env from the rock scorpionfish (Scorpionfish schlegelii), a lentiviral vector, and their applications, belonging to the field of genetic breeding in molecular biology. The envelope protein T_env has the amino acid sequence shown in SEQ ID NO.1. Based on this protein, this invention further provides corresponding membrane fusion protein particles, a system for in vitro assembly of lentiviral particles, transformants, and related kits. This invention utilizes the T_env protein derived from bony fish to replace the commonly used VSVG protein, which can significantly improve the infection and transduction efficiency of lentiviruses in bony fish cells, thereby achieving more efficient gene delivery. Furthermore, since this protein is an endogenous Env protein from the rock scorpionfish, it can avoid the immune rejection response of the host to foreign proteins, thus also possessing the potential for application in the in vivo environment.

The name of the invention: "Neutralization of viruses through oxidation-reduction reaction on the virus envelope" suggests its use in medicine, both in the human and animal fields. This is not only a specific use, but also from the point of view of the dosage regimen, the method of dosage, a new group of patients, of component No. 1 - Cu2+ obtained in a solution of copper sulfate pentahydrate in distilled water, where copper must have at least two free ions and component No. 2 - L-ascorbic acid for neutralization of viruses through oxidation-reduction reaction on the virus envelope, which is characterized by the fact that it ensures the destruction of the virus envelope and thus the inhibition of viruses in humans and other warm-blooded animals. Both substances are administered in a non-toxic concentration appropriate for the human and animal organism and with an appropriate time interval, so that the most suitable conditions for the oxidation-reduction reaction on the virus envelope are created and maintained. The use of these two components establishes a scientifically proven premise for the successful prevention and treatment of infection with various types of enveloped viruses and the diseases they cause.