93 results about "Helicase" patented technology

Disclosed herein are certain thiadiazolyl derivatives Formula (I):that inhibit DNA Polymerase Theta (Polθ) activity, in particular inhibit Polθ activity by inhibiting ATP dependent helicase domain activity of Polθ. Also, disclosed are pharmaceutical compositions comprising such compounds and methods of treating and / or preventing diseases treatable by inhibition of Polθ such as cancer, including homologous recombination (HR) deficient cancers.

The present invention relates to modified Dda helicases which can be used to control the movement of analytes such as polynucleotides. The modified Dda helicases are used in analyte detection and characterisation. The present invention also relates to novel protein pores and their uses in analyte detection and characterisation. The invention particularly relates to an isolated pore complex formed by a CsgG-like pore and a modified CsgF peptide, or a homologue or mutant thereof, thereby incorporating an additional channel constriction or reader head in the nanopore.

The present invention relates to compounds of the Formula I, and pharmaceutically salts thereof: I wherein RS, R1, R2, R3, R4 and X are each as defined herein. The compounds of the present invention inhibit WRN. The novel therapeutic compounds are therefore useful for the treatment and / or prevention of diseases and conditions in which WRN activity is implicated, such as, for example but not limited to, the treatment and / or prevention of cancer. The present invention also relates to pharmaceutical compositions comprising the novel therapeutic compounds defined herein, to processes for synthesising these compounds and to their use for the treatment of diseases and / or conditions in which WRN activity is implicated.

The invention provides a bifidobacterium animalis subspecies HX-BA21, and the preservation number of the bifidobacterium animalis subspecies HX-BA21 is CGMCC (China General Microbiological Culture Collection Center) NO.32958. The invention discloses bifidobacterium animalis subspecies HX-BA21 containing exosome metabiotics and an exosome-containing fermentation compound obtained by fermenting gastrodia elata through the HX-BA21. The fermentation compound comprises a probiotic protective layer (a core layer), an exosome delivery layer (a shell layer) and a prebiotics sustained release layer (a cocoon layer) from inside to outside. The probiotic protection layer comprises a sodium alginate-milk fat globule membrane compound and animal bifidobacterium subsp.animalis; the exosome delivery layer comprises a gelatin-chitosan compound and a gastrodia elata and probiotic mixed exosome; the prebiotic sustained-release layer comprises an octenyl succinic anhydride starch / polyvinyl alcohol compound and inulin. The compound can start cell repair by improving the cell migration rate, up-regulate DNA helicase and telomere related gene expression, delay premature senescence and delay cell senescence caused by D-galactose by adjusting the oxidative stress level.

The invention discloses a corynebacterium glutamicum whole genome random mutation tool and application thereof, and belongs to the technical field of genetic engineering and biological mutagenesis. DsDNA is unwound in the transcription process based on DNA helicase, DNA adenine deaminase and the DNA helicase are fused, and whole-genome random mutation of corynebacterium glutamicum is achieved. The whole genome random mutation method disclosed by the invention is applied to mutagenesis of an original strain of Corynebacterium glutamicum ATCC 13032, and a mutant strain of which the biomass is 1.95 times of that of WT (OD600 is 2.2) and 1.99 times of that of WT / pXMJ19 (OD600 is 2.16) when being cultured under the condition that the pH value is 5.5 is obtained. The corynebacterium glutamicum whole genome random mutation method disclosed by the invention has important guiding significance for screening other mutation strains with enhanced robustness.

The present disclosure provides 3,7-disubstituted 2-oxo-2H-chromenyl compounds of Formula I or Formula II as inhibitors of helicases, such as SF3 and / or SF6 helicases, and more particularly, for example, CMG helicase and HPV El helicase, useful in treating medical disorders such as cancers or papilloma virus infections, as well as methods of making and using said compounds.

A method for moving a polynucleotide through a transmembrane pore, comprising: under the control of an electric field force, moving a polynucleotide, which is linked to a helicase variant, through a transmembrane pore, wherein the helicase variant does not have active unwinding activity or translocation activity.

This disclosure pertains to the field of gene sequencing technology and discloses the KphPif1 helicase and its applications. This disclosure relates to a modified helicase, a polynucleotide encoding the helicase, a recombinant expression vector, and a construct capable of expressing the modified helicase and used to construct recombinant cells expressing the helicase. The modified helicase disclosed herein allows target polynucleotides to pass through nanopores in a controllable and stepwise manner, stabilizing polynucleotide movement and preventing detachment from the polynucleotide. Furthermore, it features a wide current range, high decoding accuracy, fast perforation speed, and high sequencing efficiency.

Provided are a helicase mutant, a preparation method therefor, and use thereof in high-throughput sequencing. The helicase mutant has at least one cysteine on a surface of a three-dimensional structure of an amino acid sequence as set forth in SEQ ID NO: 1, the at least one cysteine being substituted with alanine. The cysteine is C133, C164, C292, C323, and / or C347. Preferably, the amino acid sequence of the helicase mutant is as set forth in SEQ ID NO: 6. The helicase mutant exhibits excellent DNA unwinding activity, good protein uniformity, reduced cross-linking interactions between protein molecules, enhanced adaptability with perforin, improved sequencing stability, as well as integrity and continuity of electrical signals. Consequently, it achieves a better sequencing performance. It can be utilized for the control and characterization of nucleic acids and applied in single-molecule nanopore sequencing.

The invention discloses application of ATP-dependent DNA helicase RECG in improvement of agronomic traits of gramineous crops, corn overexpression helicase RECG or enhancement of enzyme activity can improve grain yield and plant biomass, and the application is of great significance to cultivation of new high-yield corn varieties.

The present disclosure provides technologies for genetic modification that use a helicase beta-wing element (HbW element). Provided technologies enable genetic modification without a need for introduction of one or more breaks into any genetic material being modified.

The invention discloses pharmaceutical application of RNA helicase DHX8, including application of the RNA helicase DHX8 in aortic dissection diagnosis, treatment and drug development. It is found for the first time that DHX8 is significantly down-regulated in aortic dissection patients, animal models and vascular endothelial cells, and overexpression of DHX8 can effectively up-regulate endothelial cell tight connection related genes and repair the endothelial barrier function. The Si DHX8 is used for transfecting human umbilical vein endothelial cells (HUVECs), and the DHX8 is knocked down, so that the tight connection gene OCLN is obviously reduced; when the OE DHX8 plasmid is used for transfecting the HUVECs and overexpressing the DHX8, the tight connection genes OCLN, JAM-A, ZO-1 and VE-cadherin are found to be obviously up-regulated. The DHX8 is used as a new target for aortic dissection diagnosis and treatment, and a detection reagent, a gene therapy vector and an agonist drug of the DHX8 have important clinical transformation values.

The disclosure provides compounds of Formula I or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising such compounds, and use of such compounds for treating cancers treatable by inhibition of WRN helicase.

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.

This invention discloses a method for rice to withstand heat stress. RMI1 Genes and their applications. Among them... RMI1 The nucleotide sequence of the gene is shown in SEQ ID No. 1, and the amino acid sequence of the protein it encodes is shown in SEQ ID No. 2; this invention verifies RMI1 The function of the gene, RMI1 protein is located in the cell nucleus, rmi1-1 In mutants RMI1 The deletion of 33 base pairs in the gene results in the loss of 11 amino acids in the RMI1-1 protein, making... rmi1-1 High temperatures during the seedling stage cause a large number of abnormal chromosomes to adhere and fragment during the late mitotic phase of root tip cells, resulting in stunted plant growth and development. rmi1-1 High temperatures during the reproductive growth period of plants lead to a large number of chromosome fragments and adhesions in the late stage of meiosis I, resulting in sterility; high temperatures also affect the interaction between RMI1-1 protein and topoisomerase TOP3α and helicase RECQ4. rmi1-cr3 Frameshift mutations lead to abnormal embryo and endosperm development; overexpression RMI1 This invention can enhance the heat resistance of rice. RMI1 The analysis of gene function provides genetic resources for the breeding of heat-resistant rice varieties.

Provided is a method for predicting sensitivity of a cancer cell to a helicase inhibitor, the method comprising the step of:predicting a cancer cell having at least one mutation detected selected from the first group consisting of TTK mutation and RAD 50 mutation, as having sensitivity to a helicase inhibitor, orpredicting a cancer cell having at least one mutation detected selected from the second group consisting of RAD 50 mutation, MRE 11 mutation, NBN mutation, DNA 2 mutation and RBBP 8 mutation, as having sensitivity to a helicase inhibitor.

This invention application discloses a gene regulating maize kernel development. ZmRH51 This application focuses on the encoded proteins, functional markers, and applications of maize kernel mutants. m223 Using this as the basic material, its heterozygotes were crossed with Zheng 58 (Z58) to construct the F2 segregating population. Phenotypic identification and cytological observation were performed on the progeny segregating population. Controlling populations were obtained through genetic analysis, BSR-seq analysis, and map-based cloning. m223 Genes with mutant phenotypes ZmRH51 This gene is located in the nucleolar region and encodes an RNA helicase belonging to the DEAD-Box gene family. Studies have shown that... ZmRH51 It participates in ribosome assembly and can influence the processing of pre-rRNA in maize kernels; and further mining yields... ZmRH51 The superior allelic variant genotype of this gene in terms of grain thickness can be utilized to improve grain thickness and 100-grain weight, thereby increasing yield. Furthermore, the distribution and utilization potential of different haplotypes in inbred lines were studied, providing technical support and excellent germplasm resources for the utilization of this gene.

The invention discloses an RNA helicase inhibitor purification process based on solvent extraction, and relates to the technical field of RNA helicase inhibitors, the RNA helicase inhibitor purification process comprises a shell, an extractor, a washer, a first motor, a first delivery pipe, a first discharge pipe, a first rotating rod, a first stirring impeller and a liquid pump; the extractor is fixedly connected to the interior of the shell; the washer is fixedly connected to the right side of the extractor in the shell; an extraction function and a washing function are integrated in the same device through an integrated structural design, and an extracted solvent phase containing a target object can directly enter a washing link in the device without being transferred, so that the problems of microbial pollution, target object activity loss and residue loss caused by a transfer process in a traditional step-by-step process are effectively avoided; the purification yield and the product purity are obviously improved; the operation process is greatly simplified, the production cycle is shortened, the process complexity and the production cost are reduced, and the stability and the practicability of the RNA helicase inhibitor purification process are integrally improved.

The disclosure provides for compositions, systems, and methods for long-range targeted mutagenesis. In particular, the disclosure provides engineered compositions comprising a programmable nickase configured to introduce a single-strand nick in double-stranded DNA (dsDNA) at one or more targeted nick sites; a helicase configured to unwind a portion of the dsDNA at the one or more targeted nick sites; and a deaminase configured to introduce one or more base edits within the portion of unwound dsDNA. Also provided are vector and delivery systems comprising one or more polynucleotides encoding the components of the compositions, as well as modified cells, cell populations, animal models, pharmaceutical compositions, and kits comprising the compositions.

Protein complexes including a cytidine deaminase and a helicase. In some embodiments, the cytidine deaminase is an altered cytidine deaminase. In some embodiments, the protein complex converts 5 methylcytosine to thymine. Kits, compositions, and methods of use for the protein complexes including a cytidine deaminase and a helicase are also described.

Provided in the present invention are a nitrogen-containing compound for inhibiting WRN helicase, a pharmaceutical composition containing same, and a use thereof. Specifically, provided in the present invention are a compound shown in formula (I), a stereoisomer thereof, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a crystal form thereof, an isotopic derivative thereof, a prodrug thereof, a metabolite thereof, and a solvate or a hydrate thereof. Also provided are a composition containing the compound and the use thereof as a WRN helicase inhibitor in the prevention or treatment of related diseases.

The application discloses a novel radionuclide therapeutic drug targeting nucleolus DDX24 helicase and a preparation method and application thereof. 64 The Cu-DOTA-TDP-2 has good tumor targeting uptake specificity, and is expected to provide a precise molecular imaging method for esophageal squamous cell carcinoma and other DDX24 high-expression malignant tumors; the novel radionuclide targeted drug 177 The Lu-DOTA-TDP-2 has high radiochemical yield and specific activity, good chemical stability, high affinity for DDX24 helicase, and a simple and easy-to-operate preparation method, and can be used for the treatment of DDX24 high-expression malignant tumors; the novel radionuclide targeted drug 177 The Lu-DOTA-TDP-2 has excellent biological safety performance and good tumor inhibition effect in esophageal squamous cell carcinoma and other DDX24 high-expression malignant tumors.

The application discloses a spiro derivative as a WRN helicase inhibitor and application thereof. The spiro derivative has better WRN helicase inhibiting activity, can be used for inhibiting the growth of microsatellite instability (MSI) tumor cells by inhibiting WRN to cause high levels of DNA double-strand breaks (DSB) in the MSI cells, can be used for preventing and / or treating related cancers, especially colorectal cancer, gastric cancer, ovarian cancer and endometrial tumor, can fill the gap of specific MSI typing cancer targeting drugs, and has very good application prospect and value in the medical field.

The invention discloses a method for screening a controllable CcdB suicide switch based on deep learning, and belongs to the technical field of biology. According to the invention, a deep learning tool MuToN mutant and DNA helicase binding energy change is used for prediction and sorting, mutants with obvious decline in affinity are screened, the obtained mutants are constructed into an expression plasmid containing an inducible promoter through a site-specific mutagenesis method, the expression plasmid is transformed into an MG1655 bacterium lacking a detoxification gene ccdA, and under the condition of not adding an inducer, the expression plasmid containing the inducible promoter is transformed into the MG1655 bacterium lacking the detoxification gene ccdA, and the expression plasmid containing the inducible promoter is transformed into the MG1655 bacterium lacking the detoxification gene ccdA. Screening a strain-free toxic mutant through a coating method; the obtained mutant plasmid is transformed into MG1655 bacteria without a detoxification gene ccdA, a flat plate containing anhydrotetracycline is coated with the MG1655 bacteria, and a mutant with a high fatality rate is screened. A mutant which is moderate in toxicity, can be expressed under the background of lacking CcdA and can reactivate toxicity under an induction condition is constructed, so that a controllable suicide mechanism is realized, and the mutant can be used for on-demand self-killing of strains, construction of gRNA plasmids in a CRISPR / Cas system and sterile treatment of fermentation waste liquid.

Provided is a screening method for exploring a novel autophagy-inducing compound. A novel autophagy-inducing compound is explored by using at least one of the following properties (1)-(3): (1) the novel autophagy-inducing compound has a high binding affinity for DEAD-box-type RNA helicase; (2) bringing the DEAD-box type RNA helicase into proximity to p62 to promote interaction; and (3) promoting the formation of droplets of the DEAD-box type RNA helicase and p62.

Disclosed herein are certain thiadiazolyl derivatives of Formula (I), (II), (III), or (IV):that inhibit DNA Polymerase Theta (Polθ) activity, in particular inhibit Polθ activity by inhibiting ATP dependent helicase domain activity of Polθ. Also, disclosed are pharmaceutical compositions comprising such compounds and methods of treating and / or preventing diseases treatable by inhibition of Polθ such as cancer, including homologous recombination (HR) deficient cancers.

Disclosed herein are compounds of formula (I) that inhibit DNA polymerase theta (Pol theta) activity, particularly Pol theta activity by inhibiting ATP-dependent helicase domain activity of Pol theta. Furthermore, pharmaceutical compositions comprising such compounds, and methods of treating and / or preventing diseases treatable by inhibition of Pol [theta], such as cancers, including homologous recombination (HR) deficient cancers, are disclosed. # imgabs0 # (I).

The present invention relates to: a pharmaceutical composition for preventing or treating cancer, wherein the composition specifically inhibits ERCC3 (ERCC Excision Repair 3, TFIH Core Complex Helicase Subunit, also referred to as Xeroderma pigmentosum group B (XPB)) to inhibit the proliferation of cancer cells while inducing normal differentiation, thereby reverting the cancer cells into normal-like cells (or normal functional cells); and a method for screening a drug for reverting cancer cells into normal-like cells (or normal functional cells) by inhibiting the proliferation of the cancer cells while inducing normal differentiation.

The invention belongs to the technical field of biological detection, and particularly relates to an ultrashort helicase dependent isothermal amplification detection reagent based on CRISPR / Cas12a. According to the invention, a large amount of ultrashort amplicons are generated through the usHDA reaction and are combined with the CRISPR / Cas12a detection technology, the reaction is rapid, the whole experiment time does not exceed one hour, the experiment time is greatly shortened, the defect of insufficient specificity of the traditional HDA technology is overcome, the uncovering operation is avoided, and the pollution risk is reduced.

This invention relates to a novel mRNA composition and its production method useful for developing and manufacturing RNA-based anti-viral and / or anti-cancer vaccines and medicines. This invention includes two types of mRNA constructs, namely “5′-hairpin messenger RNA (5hmRNA)” and “messenger-hairpin-messenger RNA (mhmRNA)”, respectively. Both of 5hmRNA and mhmRNA contain at least a hairpin-like stem-loop RNA structure. The 5hmRNA contains at least a stem-loop RNA structure in the 5′-UTR of a protein / peptide-coding mRNA, while the mhmRNA contains a middle stem-loop structure flanked with two protein / peptide-coding mRNA sequences on both sides. In mhmRNA, the first 5′-mRNA preferably encodes an RNA replicase, for amplifying the second 3′-mRNA in transfected cells. After transfection into target cells, 5hmRNA and mhmRNA can be further translated into at least a desired protein / peptide. To produce highly structured 5hmRNA and mhmRNA, a novel PCR-IVT methodology has been developed and used with a specially designed RNA polymerase-helicase mixture reaction.