34 results about "CccDNA" patented technology

The invention relates to an HBV magnetic bead as well as a preparation method and application thereof. The HBV magnetic beads are HBV magnetic beads with molecular tag primer sequences, poly (dT) and N HBV specific capture probes are coupled and modified, and N is a positive integer and is greater than or equal to 1. The HBV specific capture probe is selected from the following groups: (a) a pgRNA probe; (b) an S probe; (c) an X probe; (d) an rcDNA probe; (e) a cccDNA probe; wherein the pgRNA probe targets a positive chain pgRNA region of the HBV, the S probe targets a positive chain S region of the HBV, the X probe targets a positive chain X region of the HBV, the rcDNA probe targets a negative chain rcDNA region of the HBV, and the cccDNA probe targets a negative chain cccDNA region of the HBV. By adopting the novel HBV magnetic bead, the enrichment of HBV sequences can be greatly improved.

The present invention relates to a viral gene therapy vector for removing hepatitis B viruses, a preparation method therefor, and the use thereof, aiming to solve the problem in which existing viral gene therapy vectors can only inhibit the replication of hepatitis B viruses, but cannot remove virus cccDNA. The vector comprises a promoter, an intron, an enhancer, a nuclear localization signal (NLS) functional domain encoding gene of PGLYRP2 protein, an HBV DNA binding domain encoding gene of the PGLYRP2 protein, a secretory signal peptide functional domain encoding gene of the PGLYRP2 protein, an HBV nucleocapsid-binding functional domain encoding gene of the PGLYRP2 protein, and an IRES fragment. The viral gene therapy vector can remarkably promote the removal of HBVs in the liver of mice and is used for treatment of hepatitis B virus infection.

The present disclosure relates to siRNA for inhibiting hepatitis B virus and uses thereof. In particular to an oligonucleotide for inhibiting HBV or a pharmaceutically acceptable salt thereof, the oligonucleotide comprises an antisense strand, the antisense strand comprises at least one modified nucleotide, and the nucleotide sequence of the antisense strand comprises a sequence or fragment as shown in any one of SEQ ID NO: 3-35. According to the present invention, the siRNA provides significant inhibition effects for HBsAg, HBV DNA and HBeAg generated by cccDNA and host genome integrated HBV DNA in vivo and in vitro, the drug effect is lasting, and compared with the original sequence, the optimized sequence improves the inhibition effect and the drug effect period, and reduces the off-target toxicity;

Use of PGLYRP2 gene and a related drug thereof. The present invention relates to the field of biopharmaceuticals, and in particular, to use of the PGLYRP2 gene and the related drug thereof. The present invention aims to solve the problem that existing drugs can only inhibit the replication of hepatitis B virus and cannot eliminate viral cccDNA. The PGLYRP2 gene is used for preparing a drug for treating a hepatitis B virus infection. The PGLYRP2 gene is used for preparing a drug for eliminating hepatitis B virus cccDNA. Also provided is a gene therapy vector for eliminating hepatitis B virus. The gene therapy vector comprises a promoter, an intron, an enhancer, and a PGLYRP2 gene encoding region. The HBV virus inhibition function and the cccDNA-eliminating effect of the PGLYRP2 protein are defined, so that the elimination of HBV in liver cells and a mouse liver can be significantly promoted.

Provided herein are methods of detecting sources of hepatitis B virus (HBV) surface antigens (HbsAgs) in samples. Some exemplary embodiments include amplifying HBV transcript nucleic acids in or from a sample and quantifying an amount of HBV transcript nucleic acids transcribed from HBV cccDNA and an amount of HBV transcript nucleic acids transcribed from the HBV iDNA. Related systems and other aspects are also provided.

The invention discloses a method and system for analyzing next-generation sequencing data and application. The specific detection of the transcriptional activity of the cccDNA is realized by utilizing the two characteristic sequences, a new analysis method is provided for evaluating the antiviral treatment effect and judging functional cure, and individualized treatment and new drug research and development can be guided. In addition, the method is also suitable for designing specific quantitative PCR probes and primers, the cccDNA transcriptional level is evaluated by detecting characteristic fragments, and a more convenient detection means is provided for clinical laboratories.

The application provides an application of AU15330 in preparation of a medicine for treating hepatitis B or inhibiting HBV. The application proves that AU15330 can inhibit the transcription activity of cccDNA by inhibiting the accessibility of HBV cccDNA chromatin, thereby reducing the replication ability of HBV. The application provides a new medicine for treating hepatitis B and related diseases such as hepatocellular carcinoma, and the target point also provides a new selection for the development of other such medicines.

The invention provides a space-time controlled recombinant cccDNA transgenic animal model as well as application and a preparation method thereof.

The present invention relates to enhanced antisense oligonucleotides that are complementary to the Far Upstream Element-Binding Protein 1 (FUBP1) and are capable of reducing a FUBP1 target nucleic acid, such as FUBP1 mRNA. The invention relates to enhanced antisense oligonucleotides targeting FUBP1 or conjugates thereof for use in treating and / or preventing a hepatitis B virus (HBV) infection, in particular a chronic HBV infection. The invention in particular relates to the use of the enhanced antisense oligonucleotides targeting FUBP1 or conjugates thereof for destabilizing cccDNA, such as HBV cccDNA. The invention further relates to enhanced antisense oligonucleotides targeting FUBP1 or conjugates thereof for use in treating cancer. A pharmaceutical composition and its use in the treatment and / or prevention of an HBV infection, or its use in the treatment of cancer is also disclosed.

To provide a COPS3 inhibitor to be used in treating HBV infection particularly chronic HBV infection.SOLUTION: Provided is use of a COPS3 inhibitor for destabilizing a cccDNA (covalently closed circular DNA) such as an HBV cccDNA. Also provided is a nucleic acid molecule which is complementary with COPS3, and can reduce a COPS3 mRNA level. A pharmaceutical composition and use thereof in treating HBV infection are also included.SELECTED DRAWING: None

The present invention relates to a RTEL1 inhibitor for use in treatment of an HBV infection, in particular a chronic HBV infection. The invention in particular relates to the use of RTEL1 inhibitors for destabilizing cccDNA, such as HBV cccDNA. The invention also relates to antisense oligonucleotides which are complementary to RTEL1 and capable of reducing a RTEL1 mRNA. Also comprised in the present invention is a pharmaceutical composition and its use in the treatment and / or prevention of a HBV infection.

To provide a novel agent for inhibiting cccDNA existing in the nucleus of a cell.SOLUTION: An agent for inhibiting HBV-derived cccDNA includes a ferritin light chain inhibitor to inhibit a ferritin light chain. The ferritin light chain inhibitor is an expression inhibitor to inhibit the expression of the ferritin light chain. A pharmaceutical composition for HBV infection includes the agent for inhibiting HBV-derived cccDNA.SELECTED DRAWING: Figure 1

The invention provides an integrated DNA interference excluding in-situ hybridization probe and an in-situ hybridization method for detecting hepatitis B virus cccDNA, the in-situ hybridization probe is designed based on a Basescope detection method, and comprises an HBV cccDNA probe specifically targeting an integrated breakpoint of HBV negative chain DNA, an HBV DNA probe targeting an HBV negative chain, an HBV cccDNA probe targeting an HBV negative chain, an HBV cccDNA probe targeting an HBV negative chain, an HBV cccDNA probe targeting an HBV negative chain, and an HBV cccDNA probe targeting an HBV negative chain. The HBV RNA probe with the targeted HBV positive strand gap structure and the matched ribonuclease of the HBV RNA probe can be used for detecting cccDNA and integrating HBV DNA after being treated, and the targeting sequences of the HBV cccDNA, the HBV DNA and the HBV RNA probe are respectively shown as SEQ ID No.1 to SEQ ID No.3. The in-situ hybridization probe and the in-situ hybridization method can be applied to screening medicines for preventing or treating hepatitis B virus infection and researching the life cycle of the hepatitis B virus, so that the understanding on the characteristics of the hepatitis B virus is promoted, and the evaluation on a treatment strategy is optimized.

The present invention relates to the field of virology, particularly to the field of hepatitis B virus treatment. A model and method for screening HBV cccDNA inhibitors are provided. According to this screening model and method, split luciferase detection is used as a surrogate indicator for HBV cccDNA detection, enabling high-throughput screening of cccDNA-targeting drugs.

The invention discloses a stimuli-responsive hepatic cell targeted light-controlled nano-carrier UACPG and a preparation method and application thereof, the preparation method comprises the following steps: extending the 3'end of sgRNA to synthesize sgRNAL, the extending part is an ASO base complementary pairing sequence, and then preparing Cas9 / sgRNA / ASO through DNA-RNA hybridization; the preparation method comprises the following steps: preparing Nd < 3 + >-sensitized core-shell UCNPs nanoparticles which take NaYF4: Tm / Yb / Ca as a core and NaYF4: Nd / Yb as a shell; dBCO group modification is carried out on the UAC nano particles, Cas9 / sgRNA / ASO is efficiently coupled through click chemistry, and UAC nano particles are synthesized; finally, the surfaces of the UAC nano particles are coated with galactosylated polyacetamide (PVAm-Gal), and the UACPG nano particles are obtained. Safe, efficient and high-targeting delivery of Cas9 / sgRNA / ASO in vivo and in vitro is realized; and the traceless release of ASO and Cas9 / sgRNA is realized under the irradiation of NIR, and the purposes of blocking virus replication, supplementing in a cccDNA pool and removing the existing cccDNA are achieved by targeting HBV pgRNA and HBV cccDNA respectively.

The invention discloses an HBV cccDNA extraction and detection method, and belongs to the technical field of bioengineering. The method comprises the following steps: carrying out cytoplasm-nucleus separation, extracting HBV cccDNA in a cell nucleus, carrying out real-time fluorescent quantitative PCR (Polymerase Chain Reaction), and judging a result. Compared with other HBV cccDNA detection methods, the HBV cccDNA extraction and detection method established by the invention has the advantages that the experiment time is greatly shortened, the experiment cost is reduced, the experiment operation and the use of experiment instruments are simplified, the method is simple to operate and the like, and meanwhile, the detection sensitivity meets the scientific research requirement. The method also has a good application prospect in the aspect of screening and detecting the HBV cccDNA inhibitor.

The present invention relates to enhanced antisense oligonucleotides that are complementary to Far Upstream Element-Binding Protein 1 (FUBP1) and can reduce FUBP1 target nucleic acids such as FUBP1 mRNA. [Solution] The present invention relates to enhanced antisense oligonucleotides targeting FUBP1 or its conjugates for use in the treatment and / or prevention of hepatitis B virus (HBV) infection, particularly chronic HBV infection. The present invention relates in particular to the use of enhanced antisense oligonucleotides targeting FUBP1 or its conjugates for destabilizing cccDNA such as HBV cccDNA. The present invention further relates to enhanced antisense oligonucleotides targeting FUBP1 or its conjugates for use in the treatment of cancer. Pharmaceutical compositions and their use in the treatment and / or prevention of HBV infection, or their use in the treatment of cancer, are also included in the present invention.

The invention belongs to the technical field of cellular immunity, and particularly relates to a DC-CIK cell culture method based on an HBV protective antibody positive healthy donor and application, the cell culture method comprises the following steps: selecting HBsAg negative and anti-HBs antibody positive healthy donor peripheral blood mononuclear cells, loading a dendritic cell (DC) by using a mixed antigen of HBcAg and HBsAg, and culturing the DC-CIK cell by using a cell culture medium. And co-culturing the DC cells and cytokine-induced killer cells (CIK) to finally obtain the allogenic DC-CIK cells. According to the invention, DC cells of healthy donors and CIK cells are co-cultured to obtain allogenic DC-CIK cells, an HBcAg and HBsAg mixed antigen loading technology is adopted to significantly improve the antigen presentation capability of the DC cells, an optimized culture system enhances the targeting killing function of the cells, and the HBsAg clearance rate and the cccDNA inhibition rate can be effectively improved in combination with nucleoside analogue treatment, so that the DC-CIK cells can be used for preparing the DC-CIK cells. The synergistic breakthrough of efficient virus removal, immune function reconstruction and low recurrence rate in hepatitis B treatment is realized.

Compositions of the disclosure include RTEL1 inhibitors for use in treatment of an HBV infection, in particular a chronic HBV infection, which may destabilize cccDNA, such as HBV cccDNA. Also provided are antisense oligonucleotides which are complementary to RTEL1 and capable of reducing a RTEL1 mRNA.

To provide a RTEL1 inhibitor for use in treatment of an HBV infection, in particular a chronic HBV infection.SOLUTION: The invention in particular relates to the use of RTEL1 inhibitors for destabilizing cccDNA, such as HBV cccDNA. The invention also relates to antisense oligonucleotides which are complementary to RTEL1 and capable of reducing a RTEL1 mRNA. Also comprised in the present invention is a pharmaceutical composition and its use in the treatment and / or prevention of a HBV infection.SELECTED DRAWING: None

The invention provides an application of AU15330 in preparing a medicine for treating hepatitis B or inhibiting HBV (Hepatitis B Virus). The application proves that AU15330 inhibits the transcriptional activity of cccDNA by inhibiting the accessibility of HBV cccDNA chromatin, so that the replication ability of HBV is reduced. The invention provides a new medicine for treating related diseases such as hepatitis B and hepatocellular carcinoma, and the provided target also provides a new choice for development of other similar medicines.

The invention relates to the technical field of medical biological detection, provides a novel application of HBV RNA, particularly relates to an application in preparation of an LLV screening kit, and further provides a kit and a detection method for performing LLV screening by quantitative detection of HBV RNA. HBV RNA can reflect cccDNA in the liver of a chronic hepatitis B patient and the level of transcriptional activity of cccDNA. In disease assessment and follow-up visit of chronic hepatitis B patients, as a non-invasive assessment means, serum HBV RNA level dynamic monitoring is helpful for early recognition of potential LLV patients, so that the patients are intervened as soon as possible and disease progression is prevented in clinical diagnosis and treatment of chronic hepatitis B.

The invention discloses an application of (R)-HTS-3 in preparation of a medicine for treating hepatitis B. The (R)-HTS-3 can inhibit the levels of HBsAg, HBeAg, HBc, 3.5 kb HBV RNA, HBV core-associated DNA and HBV cccDNA in HBV replication cells, namely can inhibit HBV replication, has low toxicity to hepatocytes, can be used for preparing the medicine for treating hepatitis B, and has a good clinical application prospect.

The present application relates to the field of virology, in particular the field of hepatitis B virus treatment. Specifically, the present application relates to a model and method for screening HBV cccDNA inhibitors. The screening model and method of the present application take split luciferase detection as a surrogate indicator of HBV cccDNA detection, and can high-throughput screen drugs targeting cccDNA.

The present invention relates to: an antiviral composition comprising spiperone as a cccDNA inhibitor; and a pharmaceutical composition which is for preventing or treating viral infections or hepatitis B, and comprises spiperone as a cccDNA inhibitor. The antiviral composition comprising spiperone according to the present invention has antiviral activity against a wide range of viruses in view of the cccDNA inhibitory efficacy and mechanism of action. In addition, the pharmaceutical composition comprising spiperone has excellent cccDNA inhibitory efficacy, antiviral efficacy, and therapeutic efficacy against viruses and thus can be effectively used for preventing or treating viral infections such as hepatitis B. In addition, spiperone has a synergistic effect with existing antiviral agents and is thus effective in treating viral infections.

To provide a SEPT9 inhibitor for use in treatment and / or prevention of a hepatitis B virus infection, in particular a chronic HBV infection.SOLUTION: The invention in particular relates to the use of SEPT9 inhibitors for destabilizing cccDNA, such as HBV cccDNA. The invention also relates to nucleic acid molecules which are complementary to SEPT9 and capable of reducing the level of a SEPT9 mRNA. Also comprised in the present invention is a pharmaceutical composition and its use in the treatment of a HBV infection.SELECTED DRAWING: None

Disclosed herein is a method of treating human chronic hepatitis B virus infection by reducing or eliminating cccDNA in liver cell of an HBV infected patient for 3 months or longer.

This invention relates to pharmaceuticals and methods for clearing hepatitis B virus (HBV) cccDNA from the livers of hepatitis B virus-infected individuals. Specifically, this invention provides the use of HBV entry inhibitors that inhibit HBV entry into hepatocytes and, optionally, immunomodulatory agents that regulate anti-HBV immunity in the preparation of pharmaceutical combinations or kits used in methods for clearing HBV cccDNA from hepatitis B patients. This invention also provides corresponding pharmaceutical combinations and kits for the above-mentioned uses.

This invention relates to enhancing antisense oligonucleotides that are complementary to distal upstream element-binding protein 1 (FUBP1) and capable of reducing FUBP1 target nucleic acids, such as FUBP1 mRNA. This invention relates to enhancing antisense oligonucleotides or conjugates thereof targeting FUBP1 for the treatment and / or prevention of hepatitis B virus (HBV) infection, particularly chronic HBV infection. This invention particularly relates to the use of said enhancing antisense oligonucleotides or conjugates thereof targeting FUBP1 for destabilizing cccDNA, such as HBV cccDNA. This invention further relates to enhancing antisense oligonucleotides or conjugates thereof targeting FUBP1 for the treatment of cancer. This invention also includes a pharmaceutical composition and its use in the treatment and / or prevention of HBV infection, or its use in the treatment of cancer.

The present disclosure relates to siRNA for interfering with hepatitis B virus and uses thereof. Specifically, the invention relates to an oligonucleotide for inhibiting HBV or a pharmaceutically acceptable salt thereof, the oligonucleotide comprises an antisense strand, and the antisense strand has a sequence as shown in any one of SEQ ID NO: 251-345 or a fragment thereof, or a modification sequence of the sequence or the fragment thereof. The siRNA has a remarkable inhibition effect on HBsAg, HBV DNA and HBeAg generated by HBV DNA integrated by cccDNA and a host genome in vivo and in vitro, and the drug effect is lasting.