49 results about "DNA replication" patented technology

Disclosed herein are prokaryotic homologs of viperin (pVips), and nucleotide and nucleoside analogs produced from pVips. These nucleotide and nucleoside analogs stop nucleotide chain synthesis and provide host cells with resistance to viral infections by targeting actively replicating viral genome. Further, these nucleotide and nucleoside analogs decrease DNA replication in malignant cells. Further disclosed are methods of identifying pVips, and nucleotide and nucleoside analogs produced thereof.

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 present invention relates to cells comprising an orthogonal DNA replication machine, linear plasmids replicable by said machine, uses of said cells and said linear plasmids, methods of maintaining linear plasmids in cells, methods of evolving sequences of interest, and methods of preparing polypeptides or nucleic acids. The invention also relates to error-prone DNA polymerases, nucleic acids encoding said polymerases and uses thereof.

An agent that generates DNA replication stress and / or inhibits pathways involved in DNA replication stress tolerance for use in a method of treating a patient with cancer. The treatment comprises: determining whether the cancer expresses HORMAD1; and, if so, administering to said patient an agent that generates DNA replication stress and / or inhibits pathways involved in DNA replication stress tolerance.

The curcumin-coupled copper-gold bimetallic nanoszyme AuCu-Cur prepared by the application can remove ROS and relieve oxidative stress, prevent further damage to DNA, and introduce human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUCMSC-EVs) to improve the bioavailability. In the system, curcumin can repair damaged DNA by promoting the expression of NEIL3. In addition, the vesicles themselves are rich in various tissue repair-related proteins and RNAs, which can promote DNA replication of notochordal cells (NPCs), reverse the aging state and stimulate extracellular matrix synthesis. In the IVDD model induced by rat tail vertebra puncture, we confirmed that the material has strong antioxidant and DNA repair capacity and can effectively delay cell aging, thereby relieving the progression of IVDD. Compared with existing intervertebral disc biomaterial treatments, the present scheme can realize continuous DNA repair, which is an active, multi-target repair program that not only interrupts the vicious cycle of intervertebral disc degeneration but also promotes tissue transformation to regeneration.

The invention discloses a novel application of ginkgo biflavone in lung cancer treatment, belongs to the technical field of medicines, and researches show that ginkgo biflavone can target CDC7 and is a novel targeted medicine. It is confirmed for the first time that ginkgo biflavone regulates and controls the thermal stability and enzymatic degradation of ginkgo biflavone through targeting CDC7 kinase (binding free energies-8.3 kcal / mol), directly intervenes in the DNA replication process, and provides a natural drug lead compound for development of a novel CDC7 small-molecule inhibitor. The compound has great significance in preventing and treating malignant tumors, and has a wide prospect in the aspect of preparing medicines for treating lung tumors.

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.

The invention provides new pharmacological approaches to the treatment of benign and malignant primary brain tumors, and specifically glioblastomas (GBM) and astrocytomas in which treatment is complicated by resistance to conventional chemotherapies. To which end the invention provides compositions and methods using modulators of intracellular nitrosative / oxidative stress and modulators DNA replication and apoptosis, with examples of specific inhibitors of neuronal and inducible NO synthetases (nNOS and iNOS) that were found to be effective either when administered alone or more effective when administered in combination temozolomide (TMZ), even in tumors displaying TMZ resistance.

The invention discloses a high-yield cell-free protein synthesis system based on a cell crude extract and application of the high-yield cell-free protein synthesis system. The system comprises an escherichia coli extract, a DNA template, a buffer solution, an amino acid mixture, a nucleoside triphosphate mixture, an ATP regeneration system and antibiotics, the antibiotics are selected from compounds having inhibitory activity on metabolic processes except ribosome functions in prokaryotic microorganisms, including but not limited to one or more combinations of interfering DNA replication, DNA transcription, cell wall synthesis, energy metabolism, lipid synthesis or other non-translational related metabolic pathways. According to the method disclosed by the invention, the escherichia coli crude extract is used as a bacterial chassis, and non-essential metabolic pathways in a CFPS system are selectively inhibited by introducing different types of antibiotics, so that the yield of protein synthesis is increased.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to an alkaloid compound as a novel topoisomerase I inhibitor and a preparation method and application thereof. The alkaloid compound with a brand new structure is separated from the traditional Chinese medicine peganum harmala. Researches show that the alkaloid compound has very significant topoisomerase I inhibitory activity, and the topoisomerase I inhibitory activity is stronger than that of a positive drug camptothecin. The topoisomerase I plays a key role in DNA replication and division of tumor cells, so that proliferation of cancer cells can be blocked by inhibiting the topoisomerase I. Therefore, when the compound is used as an effective component for preparing the anti-cancer drug, a new material basis can be provided for drug research and development, the curative effect is improved, and side effects are reduced; the compound can also be used as a lead compound, high-activity anti-cancer molecules are derived through structural optimization, and the compound has important application value in the field of cancer treatment.

Certain embodiments of the invention provide a recombinant polypeptide comprising a T5 DNA polymerase amino acid sequence operably linked to a DNA helicase amino acid sequence, as well as methods of using such a recombinant polypeptide for DNA replication and / or mutagenesis. Certain embodiments of the invention provide a targeted artificial DNA replisome complex. Certain embodiments of the invention provide a targeted DNA mutagenesis system.

Compounds represented by Formula I in which A0-A2, R0-R6, L, Z and Q are defined herein. The compounds of Formula I are CHK 1 inhibitors. Therefore, the compounds can be used to treat diseases, disorders and conditions associated with continuous activation of CHK1 or with high internal DNA damage or injury during DNA replication, such as cancers.

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.

Gene amplifications are an oncogenic driver utilized by many forms of cancer in tumor development or treatment relapse. Promoting genomic instability or the proclivity to propagate genomic alterations through acquired defects in DNA repair machinery, replication licensing, or cell cycle control, gene amplifications not only drive oncogenesis, but also afford an opportunity for therapeutic exploitation. Here, CRISPR-Cas9 nickases are disclosed which selectively promote cancer cell death in a gene amplification-dependent manner. For example, CRISPR- Cas9 nickases generate a lethal number of highly toxic single-ended double-strand breaks within the genome of proliferating cancer cells harboring amplified genomic loci during DNA replication. Cas9 nickases may serve as a tumor-selective therapeutic that mitigates the collateral damage observed with conventional chemoradiotherapies and avoids chemoresistance.

The present invention discloses the mutation sites of SUV420H1 and its application in regulating the proliferation of tumor cells. The present invention provides the application of a substance capable of simultaneously site-directed mutating the K219 and R220 sites of the SUV420H1 protein in an organism or cell in any one of the following: inhibiting the proliferation of tumor cells; treating tumors, inhibiting DNA replication in tumor cells; reducing the binding of the SUV420H1 protein and the H2A.Z protein or its nucleosome. The experiments of the present invention prove that the K219R220 site on the SUV420H1 protein, which can affect the binding to H2A.Z, and mutating the K219R220 site on the SUV420H1 protein can inhibit the proliferation of tumor cells, indicating that the K219R220 site on the SUV420H1 protein can be used as a target to study specific drugs for inhibiting the proliferation of tumor cells and has potential clinical application value.

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 invention discloses a chemical small molecule compound and method for promoting mesenchymal stem cell mitochondria to be delivered to muscle cells. The chemical small molecule compound is composed of metformin, beta-nicotinamide mononucleotide, nicotinamide, ergothioneine and pyrroloquinoline quinone. The concentration range of each component is respectively as follows: 1 to 5mM of metformin, 0.1 to 1mM of beta-nicotinamide mononucleotide, 0.1 to 1mM of nicotinamide, 0.1 to 1mM of ergothioneine and 0.01 to 0.1 mu M of pyrroloquinoline quinone. The compound regulates and controls the mitochondrial function of mesenchymal stem cells through a staged treatment strategy: in the first stage (0-24 h), an AMPK signal channel is activated through metformin, the NAD + level is increased in combination with beta-nicotinamide mononucleotide and nicotinamide, and mitochondrial biogenesis is started; the pyrroloquinoline quinone is combined to promote DNA replication and protein synthesis of mitochondria, further increase the number of mitochondria and optimize functions.

The invention discloses an application of mPGES-2 as a target spot in preparation of a medicine for preventing and / or treating liver cancer. The invention proposes that mPGES-2 is a drug target for preventing and / or treating liver cancer for the first time. Experiments show that mPGES-2 knock-down significantly down-regulates expression of a cell proliferation antigen Ki67 and DNA replication marker protein PCNA, inhibits the S-phase process of cells, and further inhibits proliferation slowing caused by DNA replication of liver cancer cells; overexpression of mPGES-2 can obviously promote expression up-regulation of Ki67 and PCNA, promote the S-phase process of cells, enhance the DNA replication efficiency and finally cause obvious increase of cell proliferation; the mPGES-2 can regulate the proliferation of the liver cancer cells, so that the mPGES-2 can be used as a drug target for preventing and / or treating the liver cancer.

The application belongs to the technical field of antibacterial agents, and aims at the problem of easy loss of the antibacterial active ingredient PHMB in the prior art, and provides a guanidine compound antibacterial agent and a preparation method thereof.The guanidine compound antibacterial agent comprises a compound antibacterial active ingredient, a carrier matrix (chitosan) and a reinforcing material (silicon dioxide).In the preparation process, the zinc ion coordination stability is enhanced through methylation modification, the modified polyglycerol is covalently fixed with PHMB, and the structural stability is improved through a crosslinking network, the chitosan is coated and combined with silicon dioxide to enhance the mechanical properties and swelling resistance, PHMB destroys the bacterial cell membrane to create a penetration channel for the zinc ion ligand, the zinc ion inhibits DNA replication, and the methylated gallic acid blocks energy metabolism, so that the high-efficiency and long-acting antibacterial effect is achieved in cooperation.

The invention is suitable for the technical field of preservative production, and provides a starch food preservative and a preparation method thereof.The preservative comprises the following raw materials: a dynamic covalent bond gel carrier, a polyphenol-metal nano-cluster compound, compound enzyme, a compound extract, modified zein and a multistage pore channel starch-based adsorbent, a dynamic covalent bond gel carrier is added, dynamic imine bonds are cross-linked to form a three-dimensional network structure, when the pH of putrefying bacteria produced acid is reduced, the imine bonds are broken, antibacterial components are released, cross-linking is carried out again after the pH rises, waste of active components is prevented, a double-pH response network is formed with modified zein, and a release curve is smoother; by adding a polyphenol-zinc nano-cluster compound, the microbial enzyme activity and DNA replication are inhibited; fe2O3 in the modified zein is subjected to photo-thermal response, is heated under illumination, softens the shell to release active components, and is linked with the dynamic gel carrier to realize chemical and physical double-trigger release.

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 present invention discloses novel 5-substituted 4-hydroxycyclopent-2-en-1-one derivatives as active compounds in pharmaceutical compositions for cancer treatment. The present invention confers the cytotoxic effect of the above compounds on ovarian cancer, colorectal cancer, cervical cancer, hepatocellular carcinoma, lung cancer, bladder cancer, breast cancer, melanoma, lymphoma, leukemia, and myeloma malignant cells for inhibiting cell cycle progression in the G2 / M phase, reducing the expression of DNA replication licensing factors, and having a general cancer treatment effect. The present invention further discloses the use of the above compositions for the treatment of platinum-resistant tumors. Another aspect of the present invention is the synergistic effect of these compounds with existing cancer therapeutic agents as proteasome inhibitors. Finally, a method for synthesizing the active compounds of the above compositions is disclosed.

The present invention relates to a bacterial continuous evolution system, an orthogonal DNA polymerase and a continuous evolution method. The present invention combines an orthogonal DNA replication system with an orthogonal DNA polymerase to obtain a continuous evolution method that can contain all mutation types, can achieve mutations in long DNA fragments, has good continuity and is easy to operate. By inducing the opening and closing of DNA polymerase expression, the switching between the linear plasmid error-prone mutation process and the high-fidelity replication process is achieved, thereby achieving efficient continuous evolution of the target DNA sequence.

The invention discloses application of a host factor RAB10 in regulation and control of hepatitis B virus antigen expression and anti-hepatitis B virus. The invention provides an application of a host factor RAB10 or a coding gene thereof in regulation and control of hepatitis B virus replication or hepatitis B virus antigen expression level in host cells, and an application of the host factor RAB10 or an expression promoter thereof in preparation of drugs for resisting hepatitis B virus or inhibiting hepatitis B virus antigen. The invention also discloses application of the host factor RAB10 or the coding gene thereof as a drug target in screening drugs for resisting hepatitis B virus or inhibiting hepatitis B virus antigen. Researches show that RAB10 can significantly inhibit HBsAg expression, HBV DNA replication, HBV RNA transcription and HBs protein level, is expected to be used for developing a novel therapeutic drug for inhibiting hepatitis B virus surface antigen, and provides a new strategy for HBV functional cure.

The invention discloses a whole genome continuous mutation system based on base deaminase and application. The whole genome continuous mutation system comprises a MutaGB-A system and a MutaGB-B system. The MutaGB-A system is a series of plasmids for coding'DNA replication protein-base deaminase 'fusion protein, and whole genome continuous mutation can be formed after report strains are converted; the MutaGB-B system is a series of plasmids for coding'DNA replication protein-base deaminase-phase separation element 'fusion protein, after a strain containing'DNA replication / repair protein-phase separation element' fusion protein is converted, whole genome continuous mutation can be more efficiently introduced, and the mutation type is expanded to cover all SNP (Single Nucleotide Polymorphism) types. The whole genome continuous mutation system can improve the mutation rate of yeast strains by more than ten thousand times, is controllable and continuous, and is suitable for different biological species. By combining with a corresponding screening method, the method can be used for rapidly obtaining a target strain with specific characters.

The invention belongs to the technical field of antibacterial agents, and provides a guanidine composite antibacterial agent and a preparation method thereof in order to solve the problem that in the prior art, an antibacterial active component PHMB is prone to loss. The guanidine compound antibacterial agent comprises a compound antibacterial active component, a carrier matrix (chitosan) and a reinforcing material (silicon dioxide), in the preparation process, the coordination stability of zinc ions is enhanced through methylation modification, the modified polyglycerol covalently fixes the PHMB, the structural stability is improved through a cross-linked network, chitosan coating is combined with silicon dioxide to enhance the mechanical property and the swelling resistance, the PHMB destroys bacterial cell membranes to create a penetrating channel for zinc ion ligands, and the zinc ions inhibit DNA replication; methylated gallic acid blocks energy metabolism, and efficient and long-acting antibiosis is achieved synergistically.

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 present disclosure pertains to compounds, methods and compositions for improving on nucleic acid polymerization, including DNA replication by in vitro primer extension to generate, for example, polymers for nanopore-based single molecule sequencing of a DNA template. A nucleic acid polymerase reaction composition is provided with polymerization enhancement moieties, which allows enhanced DNA polymerase activity with nucleotide analogs, resulting in improved length of primer extension products for sequencing applications.