72 results about "Rabies virus" patented technology

The present invention provides a rabies virus G protein antigen epitope targeting completely human monoclonal antibody and applications thereof, the completely human monoclonal antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region has three complementary determining region amino acid sequences: GDISSSCFY, IHYSGST and ARHRRGYCYDSEKGGTNWFDP, and the light chain variable region has three complementary determining region amino acid sequences: GDISSSCFY, IHYSGST and ARHRRGYCYDSEKGGTNWFDP. The amino acid sequences of the three complementary determining regions of the light chain variable region are respectively as follows: QGISND, ATS and LQDYEFPLT. The fully human monoclonal antibody has efficient and broad-spectrum anti-rabies virus neutralizing activity, is high in expression, fully human-derived and good in stability, and can be used for preparing rabies virus detection products or drugs for preventing and treating rabies.

The invention discloses preparation and application of a rabies virus G protein mRNA vaccine freeze-drying preparation, and relates to the field of veterinary biological products. According to the invention, rabies virus G protein mRNA is prepared on a large scale through an in-vitro transcription technology, and an mRNA-LNP (lipid nanoparticle) delivery system is successfully constructed by adopting a microfluidic encapsulation process. Through freeze-drying protective agent formula screening (including cane sugar, trehalose and mannitol) and freeze-drying procedure parameter optimization (including pre-freezing temperature, main drying rate and secondary drying residual moisture control), the freeze-dried mRNA vaccine preparation which can stably exist under the condition of 4 DEG C is finally obtained.

The invention discloses application of mitoxantrone in preparation of an anti-rabies virus drug, reveals that clinical anti-tumor and immunosuppression drug mitoxantrone has remarkable anti-rabies virus activity for the first time, and opens up a new application field for mitoxantrone. The rigorous in-vitro and in-vivo tests prove that the mitoxantrone can inhibit virus replication in a dose-dependent manner, reduce virus gene and protein expression and remarkably improve the survival rate of infected mice in an animal model. The invention provides a new clinical application approach for mitoxantrone, provides a powerful candidate drug and a brand-new technical scheme for anti-rabies virus drugs, and has important practical significance and clinical application prospects for coping with rabies which is a major public health threat.

This utility model relates to the field of biopharmaceutical technology, and in particular to a bioreactor for monitoring rabies virus cell culture. It includes a tank and a detection mechanism. The detection mechanism is located on one side of the tank, and an assembly mechanism is located at one end of the tank. In this rabies virus cell culture monitoring bioreactor, the solution is first placed inside the tank through the detection mechanism, and a top cover is fixed to the tank via a threaded connection. The detection cover is used to seal the sample to be tested. An integrated head integrates a heating rod and is electrically connected to a battery pack to power the heating rod, thereby heating the sample inside the tank. The heating rod is located inside a sensor so that the sensor can monitor the sample status (such as gas, temperature, pressure, etc.) in real time when heated. The sensor is connected to the integrated head through a connector and a socket to form a closed detection circuit. The detection signal is transmitted to a display screen via the integrated head to display the detection result. If an abnormality occurs, an alarm light flashes.

The application discloses a single-chain antibody, the amino acid sequence of which is shown as SEQ ID NO:1, and the nucleotide sequence of which is shown as SEQ ID NO:2. The single-chain antibody against rabies virus is screened from an antibody library of immunized mice by using a phage display technology. Compared with a traditional cell fusion technology, the phage display technology is simple in operation, low in cost, short in time, and high in antibody discovery and screening efficiency. The single-chain antibody obtained by the application is low in molecular weight and immunogenicity, high in antibody specificity and affinity, and has the activity of neutralizing rabies virus, thereby providing a new idea for basic research of rabies virus and development of therapeutic drugs.

This invention discloses nanobodies against rabies virus G protein and their applications, belonging to the field of nanobody technology. The nanobodies are antibody 11G6, antibody 9F7, or antibody 9A3; the amino acid sequence of antibody 11G6 is shown in SEQ ID NO. 8; the amino acid sequence of antibody 9F7 is shown in SEQ ID NO. 13; and the amino acid sequence of antibody 9A3 is shown in SEQ ID NO. 18. This invention uses phage display technology to screen for nanobodies with high affinity and high neutralizing activity. Based on this, this invention utilizes the advantage of the small size of nanobodies and verifies their unique ability to cross the blood-brain barrier (BBB) ​​through Transwell experiments, overcoming the limitation that large molecules such as antibodies and drugs cannot cross the BBB to enter the brain. This invention provides a new drug option for the treatment of rabies virus and has significant clinical implications.

This disclosure provides an attenuated suid herpesvirus 1 (a Pseudorabies virus) wherein the TK, gl and gE genes thereof are modified relative to a parent field strain, such that the resultant virus is safe and effective for use as a live vaccine that protects swine animals from challenge with a virulent Pseudorabies virus.

The invention provides a high-yield rabies virus cell line as well as a preparation method and application thereof. Specifically, the invention provides an engineered cell for producing the recombinant rabies virus, the recombinant rabies virus with effective titer can be produced by using the cell virus through one-time passage, and a neural circuit tracing tool with excellent performance is provided for the application of the defective rabies virus in neural network reverse labeling. The research in the brain science field is promoted.

The application discloses application of siRNA for targeting and inhibiting rabies virus G gene and / or L gene in preparation of a medicine for inhibiting rabies. Furthermore, the application provides siRNA-G for targeting and inhibiting rabies virus G gene and siRNA-L for targeting and inhibiting rabies virus L gene, wherein the nucleotide sequence of the sense strand of the siRNA-G is shown as SEQ ID NO:1, the nucleotide sequence of the antisense strand of the siRNA-G is shown as SEQ ID NO:2; the nucleotide sequence of the sense strand of the siRNA-L is shown as SEQ ID NO:3, and the nucleotide sequence of the antisense strand of the siRNA-L is shown as SEQ ID NO:4. The siRNA-G and / or the siRNA-L can effectively inhibit the expression of the rabies virus G gene and the L gene, reduce the proliferation of the rabies virus, and can be used as an effective small nucleic acid medicine in the development process of an anti-rabies virus medicine.

The invention relates to a recombinant rabies virus. The recombinant rabies virus is obtained by inserting an antigen gene of feline calicivirus and an antigen gene of feline herpes virus into a genome of a rabies virus attenuated strain. The triple inactivated vaccine for preventing and treating the feline calicivirus disease, the feline herpes virus disease and / or the rabies is prepared based on the recombinant rabies virus, and after the triple inactivated vaccine is used for immunizing cats, neutralizing antibodies aiming at the feline calicivirus disease, the feline herpes virus disease and the rabies virus can be effectively induced and generated; the simultaneous immunization on the three viruses is realized.

The invention discloses an anti-rabies virus G protein nano antibody and application thereof, and belongs to the technical field of nano antibodies. The nano antibody is an antibody 11G6, an antibody 9F7 or an antibody 9A3; the amino acid sequence of the antibody 11G6 is as shown in SEQ ID NO. 8; the amino acid sequence of the antibody 9F7 is as shown in SEQ ID NO. 13; the amino acid sequence of the antibody 9A3 is as shown in SEQ ID NO. 18. According to the invention, the nano antibody with high affinity and high neutralizing activity is screened by a phage display technology. On the basis, the advantage that the size of the nano antibody is small is utilized, the unique ability of the nano antibody to penetrate through the BBB is verified through a Transwell experiment, and the defect that macromolecules such as antibodies and drugs cannot penetrate through the BBB to enter the brain is overcome. The invention provides a new drug choice for the treatment of rabies virus, and has important clinical significance.

The invention discloses an anti-rabies virus G protein monoclonal antibody, a detection reagent and application of the anti-rabies virus G protein monoclonal antibody and the detection reagent. The anti-rabies virus G protein monoclonal antibody comprises a heavy chain variable region and a light chain variable region, the amino acid sequence of the heavy chain variable region is as shown in SEQ ID No. 1; the amino acid sequence of the light chain variable region is as shown in SEQ ID No.2. The monoclonal antibody provided by the invention has high affinity and detection sensitivity to rabies virus G protein, and lays a foundation for research, development and popularization of colloidal gold test strips and fluorescence immunoassay test strips.

The invention discloses a CDR region of a nano antibody for targeting rabies virus. The invention also discloses a nano antibody aRV7, which comprises the CDR region of the nano antibody targeting the rabies virus. The invention also discloses an antibody targeting the rabies virus. The invention also discloses a polynucleotide, an expression vector, a host cell and an antibody conjugate. The invention also discloses a CDR region of the rabies virus-targeted nano antibody, a nano antibody aRV7, the rabies virus-targeted antibody, and an application of the antibody conjugate. The invention also discloses a pharmaceutical composition. The nano antibody aRV7 and the antibody targeting the rabies virus have specific recognition and binding performance on rabies virus G protein, can target the rabies virus, and can be used for preparing reagents, kits, vaccines or drugs for detecting, diagnosing, treating and / or preventing rabies virus infection.

The invention discloses a CDR region of a nano antibody for targeting rabies virus. The invention also discloses a nano antibody aRV15, which comprises the CDR region of the nano antibody targeting the rabies virus. The invention also discloses an antibody targeting the rabies virus. The invention also discloses a polynucleotide, an expression vector, a host cell and an antibody conjugate. The invention also discloses a CDR region of the rabies virus-targeted nano antibody, a nano antibody aRV15, the rabies virus-targeted antibody, and an application of the antibody conjugate. The invention also discloses a pharmaceutical composition. The nano antibody aRV15 and the antibody targeting the rabies virus have specific recognition and binding performance on rabies virus G protein, can target the rabies virus, and can be used for preparing reagents, kits, vaccines or drugs for detecting, diagnosing, treating and / or preventing rabies virus infection.

The invention provides a broad-spectrum anti-rabies virus fully-humanized monoclonal antibody and application thereof, the fully-humanized monoclonal antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region has three complementary determining region amino acid sequences: GFTFSDYE, ISSSGATK and ARVPGQQVGVDR, and the light chain variable region has three complementary determining region amino acid sequences: GFTFSDYE, ISSSGATK and ARVPGQQVGVDR. The amino acid sequences of three complementary determining regions of the light chain variable region are RAIHNY, ATS and QQYYGYPWT respectively. The fully human monoclonal antibody R06 has efficient and broad-spectrum anti-rabies virus neutralizing activity, is high in expression, fully human-derived and good in stability, and can be used for preparing rabies virus detection products or drugs for preventing and treating rabies.

The invention discloses an anti-rabies virus mutant antibody as well as a preparation method and application thereof, and belongs to the field of antibodies. The technical problem to be solved is to provide an anti-rabies virus mutant antibody with longer in-vivo half-life period and longer effective antibody concentration maintenance time. According to the key point of the technical scheme, the anti-rabies virus mutant antibody comprises a heavy chain and a light chain, and the nucleotide sequence of the heavy chain is as shown in SEQ ID NO: 1. According to the invention, a YTE mutation technology is adopted to carry out long-acting modification on the recombinant human anti-rabies virus monoclonal antibody R8. Through synthesis of heavy chain and light chain gene sequences of the mutated antibody, a mutation expression plasmid is constructed, and pharmacokinetic verification is carried out after transient transfection expression purification, so that long-acting transformation and preparation of the R8 antibody are realized, and technical support is provided for clinical application.

The application belongs to the technical field of biological medicine, and provides a photosensitizer, a targeted delivery nano platform and application. A preparation method of the photosensitizer comprises the following process: a Suzuki coupling reaction is used to synthesize an intermediate with an aldehyde group by taking a brominated or iodinated triphenylamine as a precursor and reacting with boric acid, and then a Knoevenagel condensation reaction is used to convert the terminal aldehyde group into a strong electron-withdrawing dicyanovinyl group by reacting the aldehyde group intermediate with malononitrile, so as to synthesize the photosensitizer PSs. The application takes a structure-optimized photosensitizer (used for generating ROS and inactivating viruses) and a STING agonist (used for activating the STING pathway and inducing cell death) as core treatment components, and takes a rabies virus glycoprotein peptide as a active targeting ligand, so that the "PDT-immune" synergistic inactivation of RABV can be realized.

The invention relates to a cell line for saving rabies virus and application thereof. A cell comprising, expressing and / or secreting B19G or a variant having at least 80% sequence identity thereto and retaining function is provided. According to the cell line, viruses can be efficiently rescued, and passage of the viruses is reduced.

The application discloses application of lapatinib in preparation of a rabies virus resisting medicine, and first discovers the rabies virus resisting activity of lapatinib, breaks the limitation of lapatinib only being used for treating tumors, and first proves the role of lapatinib in inhibiting rabies virus replication through in-vivo and in-vitro experiments, develops the potential application value of lapatinib in early treatment after rabies virus exposure, and provides a new use of lapatinib, i.e., using lapatinib as a candidate medicine for rabies treatment, especially specific treatment in the early stage of rabies virus infection, and fills the blank of specific treatment medicines after rabies virus exposure.

The invention discloses a CDR region of a nano antibody for targeting rabies virus. The invention also discloses a nano antibody aRV48, which comprises the CDR region of the nano antibody targeting the rabies virus. The invention also discloses an antibody targeting the rabies virus. The invention also discloses a polynucleotide, an expression vector, a host cell and an antibody conjugate. The invention also discloses a CDR region of the rabies virus-targeted nano antibody, a nano antibody aRV48, the rabies virus-targeted antibody, and an application of the antibody conjugate. The invention also discloses a pharmaceutical composition. The nano antibody aRV48 and the antibody targeting the rabies virus have specific recognition and binding performance on rabies virus G protein, can target the rabies virus, and can be used for preparing reagents, kits, vaccines or drugs for detecting, diagnosing, treating and / or preventing rabies virus infection.

The invention discloses a neurophilic virus protein-loaded selenium-containing cationic mesoporous silica nano-material, a preparation method thereof and application thereof in preparation of drugs for treating multiple sclerosis, a nano-carrier is selenium atom-containing MSN, polyethyleneimine and polyethylene glycol are used as raw materials, and a neurophilic virus protein rabies virus glycoprotein RVG29 is loaded, so that the selenium-containing cationic mesoporous silica nano-material is prepared. And constructing the nanoparticles for removing the cfDNA. Compared with traditional drugs for treating multiple sclerosis, the cationic mesoporous silica nano-material loaded with neurophilic virus protein provided by the invention is more efficient, safer and controllable when being used for anti-inflammatory treatment of multiple sclerosis, and provides a new thought and a new material for efficient intervention of clinical multiple sclerosis; the cationic mesoporous silica nano material loaded with the neurophilic virus protein can be targeted to a central nervous system to play an anti-inflammatory role, has a good antibacterial role, also has a good blood-brain barrier penetration property, and is very suitable for being applied to multiple sclerosis treatment.

The invention provides a neutralizing fully human monoclonal antibody aiming at rabies virus G protein and application thereof, the fully human monoclonal antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region has three complementary determining region amino acid sequences: GGSFSDYY, SMHSGST and AAGDYGDSGGWFES, the light chain variable region has three complementary determining region amino acid sequences: GGSFSDYY, SMHSGST and AAGDYGDSGGWFES, and the heavy chain variable region has three complementary determining region amino acid sequences: GGSFSDYY, SMHSGST and AAGDYGDSGGWFES. The amino acid sequences of three complementary determining regions of the light chain variable region are respectively as follows: QSIDRD, GAS and QQYNTWPLT. The antibody has efficient and broad-spectrum anti-rabies virus neutralizing activity, high expression, full human source and good stability, and can be used for preparing rabies virus detection products or drugs for preventing and treating rabies.

The present invention relates to a population of small extracellular vesicles (sEVs) for use in the treatment of obesity in a subject in need thereof, wherein the sEVs comprise at least one polynucleotide encoding a D168A dominant negative AMP-activated protein kinase alpha 1 (AMPKa1-DN) mutant protein operably linked and under the control of a steroidogenic factor 1 (SF1) promoter, wherein the sEVs are engineered to transiently express in their outer membrane at least one fusion protein comprising the neurotrophic rabies virus (RVG) peptide fused to lysosome-associated membrane protein 2b. Said population is highly safe and effective, as the sEVs, when administered systematically, are capable of exerting their effect in the SF1 expressing neurons located in the ventromedial nucleus of the hypothalamus.

The invention provides an anti-rabies virus fully-humanized monoclonal antibody with high neutralizing activity and application thereof, the fully-humanized monoclonal antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region has three complementary determining region amino acid sequences: GYSSINYW, IYPGDSDT and ARRSMTTPYYFDY, the light chain variable region has three complementary determining regions: GYSSINYW, IYPGDSDT and ARRSMTTPYYFDY, and the heavy chain variable region has three complementary determining regions: GYSSINYW, IYPGDSDT and ARRSMTTPYYFDY. The amino acid sequences of three complementary determining regions of the light chain variable region are respectively as follows: QSVSSSY, AAS and HQYGRSPPLT. The fully human monoclonal antibody has efficient and broad-spectrum anti-rabies virus neutralizing activity, is high in expression, fully human-derived and good in stability, and can be used for preparing rabies virus detection products or drugs for preventing and treating rabies. The invention relates to an anti-rabies virus fully humanized monoclonal antibody with high neutralizing activity.

Compositions and methods of making and making nucleic acid vaccines comprising polynucleotide sequences encoding one or more structural proteins of rabies virus (RABV) and therapeutic uses for the treatment, amelioration, amelioration and / or prevention of rabies are provided.

The present application relates to a packaging cell line for efficiently propagating third-generation rabies virus and its preparation method and application. Specifically, the present application provides an engineered cell line for efficiently propagating third-generation rabies virus, wherein an exogenous expression cassette expressing B19L and a fluorescent reporter gene is integrated into the genome of the cell, which can be used for packaging and producing third-generation rabies virus with L protein deletion. The cell line of the present application can be used for efficiently propagating third-generation rabies virus, and the obtained third-generation rabies virus has low toxicity, high titer and persistent neuron labeling ability, and is particularly suitable for neuron-related functional studies.

The invention discloses an application of etoposide in preparation of anti-rabies virus drugs, and proves that the clinical anti-tumor drug etoposide has remarkable anti-rabies virus activity on cell and animal levels for the first time, and plays an antiviral role in vitro and vivo by inhibiting virus replication and reducing virus gene and protein expression. The invention provides a brand-new medical application for etoposide, namely provides a new medicine and a technical scheme for preparing a rabies virus, and has important significance for solving the problem of clinical treatment of rabies.

This invention discloses a monoclonal antibody against rabies virus N protein, a detection reagent, and their applications. The monoclonal antibody against rabies virus N protein includes a heavy chain variable region and a light chain variable region; the amino acid sequence of the heavy chain variable region is shown in SEQ ID No. 1; the amino acid sequence of the light chain variable region is shown in SEQ ID No. 2. This invention provides a monoclonal antibody with high affinity and detection sensitivity against rabies virus N protein, laying the foundation for the research and development and promotion of colloidal gold test strips and fluorescent immunoassay strips.

The invention discloses a CDR region of a nano antibody for targeting rabies virus. The invention also discloses a nano antibody aRV29, which comprises the CDR region of the nano antibody targeting the rabies virus. The invention also discloses an antibody targeting the rabies virus. The invention also discloses a polynucleotide, an expression vector, a host cell and an antibody conjugate. The invention also discloses a CDR region of the rabies virus-targeted nano antibody, a nano antibody aRV29, the rabies virus-targeted antibody, and an application of the antibody conjugate. The invention also discloses a pharmaceutical composition. The nano antibody aRV29 and the antibody targeting the rabies virus have specific recognition and binding performance on rabies virus G protein, can target the rabies virus, and can be used for preparing reagents, kits, vaccines or drugs for detecting, diagnosing, treating and / or preventing rabies virus infection.

The invention relates to a engineered pseudorabies virus (PRV) to express protective antigens derived from viruses associated with infection in swine. The PRV recombinant vector is a triple deletion mutant and includes a deletion in the gene encoding glycoprotein gE, a deletion in the gene encoding glycoprotein gG and a deletion in the gene encoding tyrosine kinase (TK), wherein at least one heterologous antigen is inserted in at least one deletion locus. The PRV recombinant vector can include at least three heterologous antigens inserted therein. Included are methods for creating recombinant vectors, mutant viruses, and vaccines for preventing or reducing symptoms associated with viral infection in swine, in particular classical swine fever (CSF) and Porcine circovirus type 2 (PCV2).