25 results about "Hepatitis A viruses" patented technology

The invention relates to the field of biological medicine, and discloses application of bionic high-density lipoprotein nanoparticles in preparation of drugs for targeting hepatitis virus receptor-1. The bionic high-density lipoprotein nanoparticle disclosed by the invention is composed of phospholipid and apolipoprotein mimetic peptide, wherein the apolipoprotein mimetic peptide is ApoA-I mimetic peptide. According to the invention, the bionic high-density lipoprotein nanoparticles can target hepatitis A virus receptor-1 for the first time, and can deliver drugs to cells of high-expression hepatitis A virus receptor-1 to play a therapeutic role. The biomimetic high-density lipoprotein nanoparticles co-loaded with anti-inflammatory and anti-fibrosis drugs can deliver the drugs to damaged renal tubules in a targeted manner especially for damaged renal tubule epithelial cells with selective high expression of KIM-1, so that kidney injuries are effectively relieved, chronic kidney diseases are treated, disease progression is relieved, and a new solution is provided for treatment of the chronic kidney diseases.

The invention discloses a method for predicting the survival state of duck against hepatitis A virus infection. The method comprises the following steps: (1) constructing a PCA (Principal Component Analysis) prediction model by taking the contents of IFN-alpha and IFN-beta of duck blood as variables; (2) measuring the contents of IFN-alpha and IFN-beta in the duck blood to be measured; and (3) substituting the measured contents of IFN-alpha and IFN-beta in the duck blood into the prediction model, and predicting the anti-hepatitis A virus infection survival state of the duck to be detected according to the family background of the individual in combination with the output result of the prediction model. According to the method, ROC curves and corresponding AUC values of different prediction models in the aspect of predicting the survival state are compared, and the result shows that the AUC value of the PCA prediction model is the highest, and the sensitivity and the specificity are most prominent. Based on the prediction model provided by the invention, the Beijing duck individuals or strains with strong disease resistance can be rapidly screened, and the prediction model has an application prospect in duck disease resistance breeding or duck virus hepatitis prevention.

The invention discloses a primer combination and a kit for detecting hepatitis A virus and application of the primer combination and the kit. The primer combination comprises at least one of the following combinations: (a) a forward primer SEQ ID NO: 3 and a reverse primer SEQ ID NO: 4; (b) a forward primer SEQ ID NO: 5 and a reverse primer SEQ ID NO: 6. According to the primer combination, through targeted region optimization, sequence design improvement and amplification parameter matching, the core pain point of an existing HAV detection technology is solved, and the primer combination has higher application value in quality detection of clinical diagnosis and cell therapy products.

The disclosure provides binding agents (e.g., antibodies) against a human Hepatitis A virus cellular receptor 2 protein (TIM3), as well as kits and methods for using the same (e.g., immunoassays) as part of a companion diagnostic and for other applications. In some aspects, the binding agents described herein may be used in assays for detecting Non-Small Cell Lung Cancer (NSCLC) and / or other types of lung cancer, Head and Neck Squamous Cell Carcinoma (HNSCC), Hepatocellular Carcinoma (HCC) or other types of liver cancer, Renal cell carcinoma, malignant melanoma, gastro-intestinal cancer, colorectal cancer, urothelial carcinoma and other types of bladder cancer, mamma carcinoma and / or other types of breast cancer, ovarian cancer, cervical cancer, prostate cancer, pancreatic cancer, lymphoma / leukemia, malignant mesothelioma, or a cancer in another organ or cell type.

The invention discloses a digital PCR nucleic acid detection kit, and relates to the technical field of in vitro diagnosis detection, the kit comprises primers, probes, a reaction liquid and a quality control liquid, the kit is used for simultaneously detecting hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus and hepatitis E virus, the reaction liquid comprises Master Mix and sterile enzyme-free water, and the quality control liquid is used for simultaneously detecting the hepatitis A virus, the hepatitis B virus, the hepatitis C virus, the hepatitis D virus and the hepatitis E virus. The quality control liquid comprises a negative quality control product and a positive quality control product. Through cooperation of sample collection, sample treatment, digital PCR reaction system preparation, digital PCR amplification and result analysis, nucleic acid detection based on the PCR technology shortens the window period by 50-70% through direct detection of virus genetic materials, becomes a key means for early diagnosis, and adopts the technical principle of digital PCR to realize rapid detection of the virus genetic materials. Compared with a traditional fluorescent quantitative PCR and immunological detection method and a qPCR method, the detection sensitivity is improved by 10-100 times, and absolute quantification can be achieved.

The application discloses a method for constructing an animal model infected with hepatitis A virus and application thereof. Specifically disclosed is a method for constructing an animal model infected with hepatitis A virus, which comprises the following steps: encapsulating a complete genome RNA of hepatitis A virus in LNP to obtain LNP-encapsulated hepatitis A virus genome RNA; inoculating the LNP-encapsulated hepatitis A virus genome RNA into a non-human mammal to obtain the animal model infected with the hepatitis A virus. The LNP-encapsulated HAV genome RNA is obtained through gene synthesis, and is used as inoculating material of the animal infection model, so that the LNP-encapsulated HAV genome RNA is convenient to obtain and has good uniformity and repeatability. The application first establishes an animal model infected with hepatitis A virus without isolation and culture of the virus, and the virus can be directly established and amplified, and compared with a strain, the virus genome RNA is easier to obtain and safer to operate.

The present invention relates to the field of biomedicine and discloses the use of a biomimetic high-density lipoprotein nanoparticle in the preparation of a drug targeting hepatitis A virus receptor 1. The biomimetic high-density lipoprotein nanoparticle of the present invention is composed of phospholipids and apolipoprotein mimetic peptides, and the apolipoprotein mimetic peptide is an ApoA-I mimetic peptide. The present invention proposes for the first time that biomimetic high-density lipoprotein nanoparticles can target hepatitis A virus receptor 1 and deliver drugs to cells that highly express hepatitis A virus receptor 1 to exert a therapeutic effect. In particular, for damaged renal tubular epithelial cells that selectively highly express KIM-1, biomimetic high-density lipoprotein nanoparticles co-loaded with anti-inflammatory and anti-fibrotic drugs can deliver drugs to damaged renal tubules in a targeted manner, effectively reducing kidney damage, treating chronic kidney disease, and alleviating disease progression, thereby providing a new solution for the treatment of chronic kidney disease.

The invention discloses an anti-hepatitis A virus antibody and application thereof, and relates to the field of antibodies. The anti-hepatitis A virus antibody disclosed by the invention comprises a heavy chain complementarity determining region and a light chain complementarity determining region, provides an important raw material source for detection of the hepatitis A virus antibody, and has good affinity or activity.

The invention relates to the technical field of biology, and discloses a DNA molecule containing whole genome cDNA of a live hepatitis A virus attenuated vaccine strain and a preparation method and application of the DNA molecule. Whole-genome infectious cDNA cloning construction is performed on the hepatitis A H2 strain for the first time, and a recovery virus with biological characteristics similar to those of a parent H2 strain is obtained through cDNA cloning rescue obtained through construction, so that a powerful tool is provided for scientific research work and medical application related to hepatitis A viruses and attenuated live vaccines.

The present application relates to compositions and methods for detecting human parvovirus nucleic acid and for detecting hepatitis A virus nucleic acid in single or multiplex assays. In particular, the present application discloses nucleic acid oligomers specific for human parvovirus genomic DNA. Also disclosed is an assay for amplifying and detecting nucleic acid of human parvovirus genotypes 1, 2 and 3 in a biological specimen. Also disclosed are compositions for amplifying and detecting the presence of genomic DNA of human parvovirus genotypes 1, 2 and 3 in a human biological specimen.

The invention discloses a method for detecting the purity of hepatitis A virus based on IEX-HPLC, and the method comprises the following steps: filtering a hepatitis A virus purified liquid sample through a filter membrane; a strong anion exchange chromatographic column is adopted, a mixed solution of a mobile phase A and a mobile phase B is used as a mobile phase, the pH range of the mobile phase is 7.5-8.5, NaCl is adopted for gradient elution, the flow velocity is 0.5-1.5 mL / min, the column temperature is 25-40 DEG C, and the detection wavelength is 260-280 mm; and identifying the target peak by adopting an SDS-PAGE (Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis) method and a Western-Blot method, identifying the target peak of the hepatitis A virus, and calculating the purity of the hepatitis A virus. According to the method, sample treatment, target chromatographic peak qualification and detection condition optimization are combined, an efficient hepatitis A virus antigen purity analysis method is established, and the key technical problem of hepatitis A virus purity analysis in actual production is solved.

A use of a YAP pathway activator in the preparation of an anti-hepatotropic virus medicament. In in vivo and in vitro hepatotropic virus replication models, it has been found that using the YAP pathway activator can significantly inhibit the replication of hepatotropic viruses such as hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, and hepatitis E virus and the expression of viral antigens. The antiviral effect of the activator is mainly achieved by means of regulation of the YAP signaling pathway and the fact that inhibiting YAP can restore viral replication. The described YAP pathway activator may be specifically a LATS1 / 2 kinase inhibitor, such as TDI-011536 or TRULI. The YAP pathway activator has no significant cytotoxicity and has a good antiviral effect.

The present application relates to compositions and methods for detecting human parvovirus nucleic acid and for detecting hepatitis A virus nucleic acid in single or multiplex assays. In particular, the present application discloses nucleic acid oligomers specific for human parvovirus genomic DNA. Also disclosed is an assay for amplifying and detecting nucleic acid of human parvovirus genotypes 1, 2 and 3 in a biological specimen. Also disclosed are compositions for amplifying and detecting the presence of genomic DNA of human parvovirus genotypes 1, 2 and 3 in a human biological specimen.

The invention relates to a hepatitis A virus (HAV) fusion protein as well as a preparation method and application thereof, prokaryotic expression and purification are carried out based on connection and fusion of main antigen regions of HAV capsid proteins VP1 and VP3, a high-purity HAV-rVP13 fusion protein is obtained, the HAV-rVP13 fusion protein is used as a coating antigen, and an ELISA detection method for an HAV specific IgG antibody is established. By establishing an enterprise calibrator and a quality control product and calibrating by a national HAV specific IgG standard product, the established ELISA detection method can quantitatively determine the concentration of the HAV specific IgG antibody in human plasma / serum, has very high sensitivity and specificity, and can be used for quantitative detection of the HAV IgG antibody in a human plasma / serum sample.

The invention relates to the technical field of biological detection, and discloses an oligonucleotide composition, a kit and application. The composition disclosed by the invention can be used for rapidly and simultaneously detecting salmonella, shigella, entamoeba histolytica, vibrio cholerae, hepatitis A virus and hepatitis E virus in a sample with high specificity, and has relatively high sensitivity and stability. Compared with the traditional detection methods such as pathogen separation, genome sequencing and the like, the efficiency of identifying and detecting salmonella, shigella, entamoeba histolytica, vibrio cholerae, hepatitis A virus and hepatitis E virus by adopting the composition disclosed by the invention is effectively improved, the detection process is simple and convenient to operate, and the composition is suitable for large-scale popularization and application.

The invention provides a micro-fluidic chip for combined detection of hepatitis A / hepatitis E virus IgM antibody and application thereof, the micro-fluidic chip comprises a substrate and a cover plate pressed on the substrate, the substrate and the cover plate enclose to form a micro-channel, the micro-channel is provided with a marking area and a detection area, and the marking area and the detection area are arranged on the substrate. The marking area comprises a first marking area arranged on the lower surface of the cover plate and a second marking area arranged on the upper surface of the substrate, and the detection area comprises an HEV-IgM antibody detection area arranged on the lower surface of the cover plate and an HAV-IgM antibody detection area arranged on the upper surface of the substrate. An IgG antibody capture area is arranged on the upper surface of the substrate corresponding to the position right below the sample injection hole, the IgG antibody capture area is provided with a magnetic microsphere-anti-human IgG antibody, the first marking area is provided with a marked HEV antigen, the second marking area is provided with a marked anti-human IgM antibody, the HEV-IgM antibody detection area is provided with an anti-human IgM antibody, and the HAV-IgM antibody detection area is provided with an HAV antigen. A capture method and an indirect method are combined to realize joint detection of the IgM antibodies related to the two viruses.

The invention relates to the technical field of hepatitis A virus detection, and provides an application of a hepatitis A virus detection technology based on an ultra-fast reverse transcription-free exponential amplification reaction (RTF-EXPAR), which comprises a primer composition, a fragment containing HAVRNA, a conjugate DNA (BinderDNA), a trigger X (TriggerX) and a template DNA (Template X '-X'), the reagent combination is divided into a part A, a part B and a part C, the total system is 33 microliters, and the detection process is as follows: the reagents are mixed according to the sequence of the part B, the part C and the part A, and the result is interpreted through a triple nucleic acid test strip (LFD) after isothermal amplification. Through the reverse transcription-free step, the total consumed time is shortened; according to the method, expensive instruments are not needed, a base layer is adapted, the HAVRNA detection limit is as low as 1.2 * 10 <-2 > nmol, early-stage trace viruses can be detected, cross reaction is avoided, and the method is adapted to multi-scene detection.

A method of culturing wild-type hepatitis A virus (wtHAV) using induced differentiated pluripotent stem cell-derived hepatocytes. Specifically, iPSCs were used to differentiate into definitive endodermal (DE) cell, and then the DE cells were differentiated into four stages of hepatocyte progenitor (HpSC), hepatoblasts (HB), immature hepatocytes (immHep), and derived hepatocytes (dHep), and each stage cells were inoculated with wtHAV, and it was confirmed that all cells could be cultured more than the initial inoculation amount and the culture reproducibility. In addition, it was confirmed that the differentiated cells of each stage of the present invention can function as sufficient infection hosts, as the number of HAV gene copies increased after 3 days after inoculation. And thus, by inoculating HAV at each stage of differentiation and selecting the optimal time point of culture, it is possible to shorten the culture period and establish an efficient culture system with optimal effect.

The application belongs to the technical field of medicine, and particularly relates to application of a jingfang preparation in prevention or treatment of type A viral hepatitis. Pharmacological experiments show that the jingfang preparation has a significant inhibitory effect on serum HAV-DNA level of infected ducks, can significantly inhibit the activity of type A hepatitis virus, and can be used for prevention and treatment of type A viral hepatitis, has a definite clinical curative effect, and is superior to jingfang baidu powder with modifications, and has a broad clinical application prospect.

The invention discloses a construction method and application of a hepatitis A virus infected animal model. The invention belongs to the technical field of animal models, and particularly discloses a method for constructing a hepatitis A virus infected animal model, which comprises the following steps: encapsulating a hepatitis A virus complete genome RNA in LNP to obtain LNP encapsulated hepatitis A virus genome RNA, and inoculating the LNP encapsulated hepatitis A virus genome RNA into a non-human mammal to obtain the hepatitis A virus infected animal model. The LNP-encapsulated HAV genome RNA is obtained through gene synthesis, the LNP-encapsulated HAV genome RNA is used as an inoculation substance of an animal infection model, the LNP-encapsulated HAV genome RNA is convenient to obtain and good in uniformity and repeatability, the infected animal model can be directly established without separating and culturing the virus and the virus is amplified for the first time, and the virus genome RNA is easier to obtain and safer to operate compared with a virus strain.

The invention discloses a construction method of a rapid virus detection system, a rapid 1-type duck hepatitis A virus detection system, a detection method and a detection kit, and relates to the technical field of rapid pathogen detection. The construction method of the rapid detection system for the type 1 duck hepatitis A virus comprises the following steps: step 1, primary screening; 2, designing a primer; step 3, verification; step 4, construction of standard quality grains; and 5, optimizing the system, and adjusting the concentration of crRNA, the concentration of Cas12a and the reaction time of Cas12a by using standard plasmids as a positive detection template to obtain a rapid detection system with the reaction time not longer than 30 minutes. The invention also provides a detection method based on the detection system and an optimized detection kit, and the detection kit can realize rapid, accurate, high-specificity and high-sensitivity detection of the 1-type duck hepatitis A virus, and is beneficial to popularization and application.

The invention provides siRNA (small interfering Ribonucleic Acid) for inhibiting RNA (Ribonucleic Acid) of hepatitis A virus (HAV), a pharmaceutical composition containing the siRNA and a conjugate. The siRNA contains a positive-sense strand and an antisense strand, each nucleotide in the siRNA is independently modified or unmodified nucleotide, the positive-sense strand contains a nucleotide sequence I, the length of the nucleotide sequence I is equal to that of a nucleotide sequence shown in SEQ ID NO: 1, the difference between the nucleotide sequence I and the nucleotide sequence shown in SEQ ID NO: 1 is not more than 3 nucleotides, the antisense strand contains a nucleotide sequence II, and the nucleotide sequence II is a nucleotide sequence shown in SEQ ID NO: 2. The length of the nucleotide sequence II is equal to that of the nucleotide sequence shown in SEQ ID NO: 2, and the difference between the nucleotide sequence II and the nucleotide sequence shown in SEQ ID NO: 2 is not more than 3 nucleotides The siRNA, the pharmaceutical composition and the conjugate provided by the invention can be used for effectively treating hepatitis A related diseases.

This invention provides a capture probe set for whole-genome sequencing of hepatitis A virus (HAV). The nucleotide sequences of the capture probe set are shown in SEQ ID No:1 to SEQ ID No:880. This capture probe set can be used to prepare kits for whole-genome sequencing of HAV. This invention also provides a method for whole-genome sequencing of HAV using the capture probe set. The method involves liquid-phase hybridization of a total RNA library from a sample to be tested with the capture probe set. DNA fragments hybridized with the capture probe set are isolated from the hybridization reaction solution. These DNA fragments are then used as templates for capture-and-PCR amplification. The PCR products are sequenced, and after data analysis, the full-length HAV genome sequence is obtained. The capture probe set designed in this invention can capture the HAV genome. By optimizing the probe length, it can specifically enrich ultra-low copy numbers of the viral genome from high-background host nucleic acids, showing broad application prospects.

The invention discloses a hepatitis A vaccine virus titer trace detection method, a kit and application. Comprising the following steps: inoculating human diploid cells into a porous cell culture plate, and culturing to form monolayer cells; inoculating a to-be-detected hepatitis A virus sample into the porous cell culture plate with monolayer cells, carrying out virus adsorption and culture, marking as an experimental group, and taking human diploid cells not inoculated with the virus sample as a negative control group; adding acetone into the experimental group and the negative control group for incubation so as to lyse cells and fix hepatitis A viruses and antigens thereof; detecting by adopting an enzyme-linked immunosorbent assay, and calculating according to a detection result to obtain the virus titer of the hepatitis A virus sample to be detected. The method is simple and convenient to operate, a virus extraction step in a traditional method is omitted, reagents are remarkably saved, the detection flux is improved, and the method is highly related to results of a pharmacopoeia method and is suitable for vaccine process research and development and quality control.

Disclosed herein are immunogenic compositions or product combinations of engineered hepatitis A virus (HAV) and / or hepatitis E virus (HEV) nucleic acids, genes, peptides, or proteins that can be used to elicit an immune response against a HAV and / or HEV infection. Also disclosed are methods of using the immunogenic compositions or product combinations in subjects to generate immune responses against HAV and / or by administering the compositions or combinations with a nucleic acid prime and polypeptide boost approach.