19 results about "Replication cycle" patented technology

The invention relates to the field of cell engineering and gene engineering, in particular to a method for enhancing the multiplication capacity of umbilical cord mesenchymal stem cells and application. The expression or activity of the STN1 gene in the umbilical cord mesenchymal stem cells is reduced through an accelerant, and the umbilical cord mesenchymal stem cells with enhanced multiplication capacity are obtained. By knocking down the hUC-MSCs of STN1, the proliferation speed of the hUC-MSCs is higher, DNA replication is more active, the clone formation ability is higher, and the aging proportion of the hUC-MSCs can be remarkably reduced.

The invention belongs to the field of new application of medicines, and particularly relates to application of 4-hydroxyderrisin in preparation of anti-influenza virus medicines. It is found for the first time that 4-hydroxyderrisin can significantly inhibit replication and internalization of influenza A virus H1N1 and has significant anti-influenza virus activity, the median inhibitory concentrations of 4-hydroxyderrisin in MDCK cells and A549 cells are 0.60 M and 0.23 M respectively, and the 4-hydroxyderrisin is low in cytotoxicity and high in safety. Experiments show that 4-hydroxyderrisin plays a role in the early stage of a virus life replication cycle, and plays an antiviral role by inhibiting virus internalization without affecting virus adsorption and neuraminidase activity. The medicine can be prepared into a solid or solution dosage form, is used for preventing and treating influenza, and has a good application prospect.

A comprehensive teaching aid system for genetic science at least including numerous (deoxy-) ribonucleotide models that can be assembled to form DNA / RNA single strands, or to form the beautiful DNA double helix structure when numerous adjacently and oppositely connected deoxynucleotide models are attached by magnets, tRNAs, and three different plates for DNA replication, mRNA transcription and protein synthesis respectively. The (deoxy-) nucleotide model includes a phosphate model, a (deoxy-) ribose model and a base model connected in sequence. Between two adjacently disposed (deoxy-) ribonucleotide models, a (deoxy-) ribose model is connected to a phosphate model in the head-to-tail fashion to form a detachable and flexible chain structure. The base model is laterally connected to the (deoxy-) ribose model, and two base models in two oppositely disposed deoxynucleotide models are flexibly and complementarily attached.

Formulations and uses thereof are provided for supporting human natural defense against viral infections as well as providing treatment for viral infections susceptible to a lysosomotropic agent. Administration of a lysosomotropic agent, such as ammonium chloride (NH4Q), can militate against the uncoating of viruses within the lysosome of an infected cell and thereby minimize infection by viruses whose replication cycle relies upon an uncoating step in such a manner.

Formulations and uses thereof are provided for supporting human natural defense against viral infections as well as providing treatment for viral infections susceptible to a lysosomotropic agent. Administration of a lysosomotropic agent, such as ammonium chloride (NH4Cl), can militate against the uncoating of viruses within the lysosome of an infected cell and thereby minimize infection by viruses whose replication cycle relies upon an uncoating step in such a manner.

The application relates to the technical field of antibacterial peptides, in particular to application of an antibacterial peptide with antifungal activity, and discloses antifungal activity, antibiofilm activity and an action mechanism of Jelleine-Ic on Candida albicans. Jelleine-Ic shows very strong antifungal activity on Candida albicans. Jelleine-Ic destroys the integrity of the cell wall of Candida albicans and enhances the permeability of the cell membrane of Candida albicans. In addition, Jelleine-Ic interacts with DNA when entering the fungal cell, influences the expression of genes involved in DNA replication and repair, and induces the generation of active oxygen in the cell, thereby accelerating the death of the fungal cell. According to the above results, Jelleine-Ic can effectively inhibit the growth of Candida albicans and has the potential for treating fungal infections.

The present invention provides engineered T7 replisomes that contain one or more modified protein components, and E. coli based orthogonal DNA replication systems that contain such engineered T7 replisomes. Relative to known orthogonal replication systems, the engineered DNA replication systems of the invention are capable of evolving target polynucleotide sequence with enhanced mutation rates.

The invention relates to cells, such as bacterial cells, comprising orthogonal DNA replication machinery, linear plasmids that may be replicated by said machinery, uses of said cells and said linear plasmids, methods of maintaining linear plasmids in cells, methods of evolving sequences of interest, and methods of making polypeptides or nucleic acids. Orthogonal systems that are based on or derived from phage, such as phi29, that infect gram-positive bacteria are disclosed herein.

Mismatch anchoring compounds (MACs) are disclosed that recognize and bind to specific base-pair mismatches (mmBP) present within single stranded or double stranded DNA, RNA, and oligonucleotide sequences, and enable the ex vivo identification of DNA / RNA point mutations (DNAPM / RNAPM), including disease-associated, rare, and low abundance DNAPM / RNAPM, and the isolation and elimination of mmBP-positive cells. The use of MACs in vitro and in vivo (a) blocks mmBP-positive DNA replication and gene transcription / expression, (b) inhibits mmBP-positive cell proliferation, (c) reverses, prevents, and / or treats mmBP-rnediated disease, aging, and age-related disorders, (d) blocks mmBP-positive RNA and / or RNA-DNA duplex translation and inhibits the production of abnormal disease-causing proteins, (e) silence mmBP-positive genes, and (f) blocks intracellular pathogen replication. MAC-conjugates and their uses are disclosed, including MACs radiolabeled with SPECT / PET / particle-emitting isotopes for radioimaging and / or radiotherapy of mmBP-positive diseases.

The present invention relates to a technique for replicating polynucleotides within eukaryotic cells and transferring the polynucleotides between eukaryotic cells, where the polynucleotides include polynucleotide sequences encoding pores that secrete DNA and genes encoding proteins required for DNA replication. The polynucleotides may also include polynucleotide sequences that provide a desired function, such as a therapeutic effect, or polynucleotide sequences that can complement or directly replace mutated genes in eukaryotic cells. Treatment methods involving administration of the polynucleotides are also disclosed.

The current invention provides for methods and systems of inducing cell cycle exit and terminal differentiation in stem cells undergoing differentiation into various mature cell types in particular pancreatic endocrine cells. The current invention also provides for methods and systems of inducing differentiation of pancreatic endocrine cells from stem cells. The invention also provides for the cells produced by the methods that are suitable for transplantation or grafting into a subject for the prevention and / or treatment of disease, and useful for basic research and drug testing.

The invention discloses a nano antibody targeting a hepatitis B surface antigen and application of the nano antibody. The nano antibody has an amino acid sequence as shown in SEQ ID NO: 1-5, and has high affinity to HBsAg. The nano antibody not only can effectively neutralize hepatitis B virus, but also can enter cells to realize'multi-link and all-directional 'inhibition of virus life cycle, including inhibition of virus RNA transcription, protein expression, nucleocapsid assembly, DNA replication and particle secretion, and can significantly down-regulate HNF4alpha, Sp1 and other key transcription factors in host hepatocytes. The antibody can be efficiently expressed in a prokaryotic or eukaryotic system. The PEGylated derivative (such as Nb1-PEG40) can prolong the half-life period, and shows stronger effects of clearing serum HBsAg and inhibiting liver virus replication in an HBV infected mouse model. The invention provides a new strategy and drug candidate for hepatitis B treatment.

The application discloses a combined drug for treating prostate cancer and application, the combined drug is a combined drug of FEN1-IN-4 and TRi-1 administered respectively or simultaneously, the FEN1-IN-4 is an inhibitor targeting Flap endonuclease 1, and the TRi-1 is an inhibitor targeting thioredoxin (TXN) antioxidant system.The combined treatment scheme of FEN1-IN-4 and TRi-1 provided by the application firstly shows a strong antitumor effect superior to single drug in vitro experiment.FEN1-IN-4 as FEN1 specific inhibitor can block the endonuclease function of FEN1 by combining with the active site of FEN1, and can achieve significant growth inhibition to various prostate cancer cell lines such as LNCaP, 22RV-1, PC3, DU145, and the like, and TRi-1 as TXN antioxidant system inhibitor can target to destroy the oxidative stress balance of tumor cells, and the two act on different key pathways (DNA replication / damage repair pathway and antioxidant defense pathway) of tumor cells, forming a "double targeting" synergistic effect.

Mismatch anchoring compounds (MACs) are disclosed that recognize and bind to specific base-pair mismatches (mmBP) present within single stranded or double stranded DNA, RNA, and oligonucleotide sequences, and enable the ex vivo identification of DNA / RNA point mutations (DNAPM / RNAPM), including disease-associated, rare, and low abundance DNAPM / RNAPM, and the isolation and elimination of mmBP-positive cells. The use of MACs in vitro and in vivo (a) blocks mmBP-positive DNA replication and gene transcription / expression, (b) inhibits mmBP-positive cell proliferation, (c) reverses, prevents, and / or treats mmBP-rnediated disease, aging, and age-related disorders, (d) blocks mmBP-positive RNA and / or RNA-DNA duplex translation and inhibits the production of abnormal disease-causing proteins, (e) silence mmBP-positive genes, and (f) blocks intracellular pathogen replication. MAC-conjugates and their uses are disclosed, including MACs radiolabeled with SPECT / PET / particle-emitting isotopes for radioimaging and / or radiotherapy of mmBP-positive diseases.

The invention belongs to the technical field of biological medicine. More specifically, the invention relates to a method for rapidly determining the virus replication period. Through high-frequency sampling after infection and combination of virus specific fluorescent antibody labeling and continuous observation in the same visual field, the invention provides a brand-new rapid determination method for the virus replication period. The method does not need to depend on an animal model and is completely completed in an in-vitro cell system, so that the operation cost is remarkably reduced; the shortest total experiment time can be controlled within 24 hours, and the research and development efficiency is greatly improved. The determination method provided by the invention has high specificity and sensitivity, is simple and convenient to operate, low in equipment threshold and suitable for various viruses, provides a brand new method for determining the virus replication period with speed, precision and feasibility for basic research of virology and research and development of antiviral products, and has good application prospects and application values.

The present disclosure relates to compounds, methods, and compositions for improving nucleic acid polymerization, including DNA replication by in vitro primer extension to produce polymers for, e.g., nanopore-based single molecule sequencing of DNA templates. Provided are nucleic acid polymerase reaction compositions with polymerization-enhancing moieties that allow for enhanced DNA polymerase activity on nucleotide analogs, thereby improving the length of primer extension products for sequencing applications.

The application discloses application of a polypeptide and a PARP inhibitor to preparation of a drug for treating breast cancer, wherein the sequence of the polypeptide is shown as SEQ ID NO:1, and the PARP inhibitor is olaparib or talazoparib. The polypeptide can down-regulate expression of a DNA damage repair gene FANCD2 protein and block DNA interchain cross-link damage repair. The PARP inhibitor blocks DNA single strand break damage repair by inhibiting catalytic activity of PARP and is mainly used for breast cancer treatment of BRCA mutation. The polypeptide and the PARP inhibitor jointly destroy a cell replication fork protection mechanism caused by DNA damage in two different ways, so that DNA replication forks of breast cancer cells are prone to arrest and collapse, thereby causing cell death. The application shows synergistic anticancer activity in BRCA wild type and BRCA mutant breast cancer subtypes, and is expected to provide a new treatment strategy for clinical treatment of breast cancer.

The invention belongs to the technical field of cell replication inhibition, and particularly relates to a method for inhibiting replication of human parvovirus B19 in cells. According to the method, the aim of inhibiting the replication of the human parvovirus B19 in the cells can be remarkably achieved by inhibiting CRM1 or mutating any one of the 255th to 263th amino acids and / or the 285th to 297th amino acids in an NS1 protein amino acid sequence. For example, by taking an NS1 defective genome M20-NS1 as a core and combining with pHelper through a functional complementation experiment, it is found that wild type NS1 (3 * FlagB19-NS1) can restore virus DNA replication, RNA transcription and generation of filial generation virus particles; and the mutant blocks the CRM1-mediated nuclear output pathway, so that the virus genome replication level is reduced by 30%-95%, the RNA transcription is reduced by 20%-80%, and the generation efficiency of filial generation virus particles is reduced by 86%.

The invention relates to the technical field of biological medicine, in particular to application of a reagent targeting ENO1-PKM interaction in preparation of a medicine for treating HBV-related hepatocellular carcinoma, it is proved that ENO1 and PKM in HBV-related HCC are remarkably overexpressed and directly interact with each other, and ENO1 and PKM synergistically promote HCC cell proliferation, migration and invasion and HBV replication by up-regulating PCNA expression, so that the effect of treating HBV-related hepatocellular carcinoma is achieved. And a glycolysis pathway is activated. Cell experiments and nude mouse transplantation tumor model verification show that the targeting reagent can block ENO1-PKM interaction, down-regulate PCNA expression, inhibit tumor cell malignant phenotypes, reduce HBV DNA replication and HBsAg secretion level, and adjust glycolytic activity. Aiming at the core pathogenic mechanism of HBV-related HCC, the invention provides a novel metabolic treatment strategy with cancer suppression and antiviral effects, and has important clinical application value.