30 results about "Nuclear DNA" patented technology

The present invention relates to certain compounds that function as inhibitors of DHX9 activity (RNA Helicase A / RHA or Nuclear DNA Helicase II / NDH II). The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions 5 comprising them, and to their use in the treatment of proliferative disorders, such as cancer, autoimmune and infectious diseases, as well as other diseases or conditions in which DHX9 activity is implicated.

A molecular biology method, by which relative (normalized to an internal control) N6-methyladenine (6mA) level at a selected specific genomic site in a tissue sample containing numerous individual cellular genomes is accurately determined, and this level is projected to a reference “6mA level-age” curve determined earlier. The relative 6mA level of the examined individual assigns her / his (biological) age on the curve. The reference curve was previously established by determining 6mA levels of a large (>1000) number of healthy individuals with known age. On the reference curve, the relative 6mA level correlates with age; the higher the 6mA level at the tested genomic site, the higher the age of the individual analyzed. The accuracy of the measurement depends on the accuracy of the method by which 6mA level is determined.

Methods and compositions for enhancing nuclear DNA delivery are provided. Aspects of the methods include contacting a cell with a DNA to be delivered to the nucleus of the cell and an agent that modulates the activity of protein Barrier-to-Autointegration Factor (BAF) in a cell. In addition, compositions, including reagents, devices and kits thereof, that find use in practicing embodiments of the subject methods are provided.

The present invention relates to a DNA base editing composition including uracil DNA glycosylase (UDG), and a DNA base editing method using same. Specifically, the present invention relates to a DNA base editing composition including a DNA binding protein, cytosine deaminase, adenine deaminase, and UDG, or polynucleotides encoding the proteins, or a DNA base editing method using same. The present invention is useful for correcting bases in nuclear DNA or organellar DNA and particularly for correcting bases in DNA of organelles such as chloroplasts or mitochondria. In the present invention, the UDG is present independently without being fused to the DNA binding protein, the cytosine deaminase, and / or the adenine deaminase.

The present invention provides an miR 1978 inhibitor and use thereof in treating a senescence-related disease. The etiology of senescence-related diseases is proposed, and the overexpression of miR 1978 derived from the mitochondrial genome in cell line SHSY5Y is proven to give rise to decreased mRNA expression and protein levels of DHFR, KIF5C, and MSH3; as a result, SHSY5Y cell division is arrested in the G1 phase of the cell cycle, the number of cells in the G2 / M phase is significantly reduced, and meanwhile, the number of apoptotic cells is increased. Compared with a control, cells containing miR1978 have different nuclear DNA methylation states. A plurality of Alzheimer's disease-related proteins, such as APP, Tau, p-Tau, and APOE, or Parkinson's disease-related proteins, such as α-synuclein, are increased in the SHSY5Y cell line containing miR 1978, etc.

The invention relates to methods and pharmaceutical composition for the treatment of estrogen-dependent cancers, particularly estrogen receptor-related cancers such as estrogen receptor-positive (ER+) cancers, like ER+ breast cancer (ER+BC). The invention relates to the combined use of an inhibitor of the methyltransferase-like protein 3 (METTL3) and an inhibitor of the nuclear DNA topoisomerase I (TOP1) for the treatment of estrogen-dependent cancers, particularly estrogen receptor-related cancers such as ER+ cancers. The inhibition of METTL3 increases the sensitivity of ER + breast cancer cells to Topoisomerase-1 inhibitor.

The present invention relates to base editing using dead uracil DNA glycosylase (dUDG). The present invention is useful for C-to-T base editing in nuclear DNA or organelle DNA, and in particular, is useful for C-to-T base editing in organelle DNA such as chloroplasts or mitochondria. The present invention also relates to a UDG variant and a novel DNA base editing use thereof.

The present invention relates to a base editing composition having an activity of editing an adenine (A) base of DNA into a guanine (G) base, and a base editing method using the same. The present invention has bases for editing nuclear DNA or organelle DNA, in particular bases for editing organelle DNA such as chloroplast or mitochondria. According to one aspect of the present invention, a base editing composition comprises a DNA binding protein, a cytosine deaminase, an adenine deaminase, and a uracil DNA glycosylase (UDG), and has an activity of selectively editing only an adenine base without substantially editing a cytosine (C) base. The present invention also provides a system for editing an adenine base of a plant cell DNA into a guanine base using a single fusion protein comprising a DNA binding protein, a cytosine deaminase and an adenine deaminase.

The invention relates to the technical field of biomedical detection, in particular to application of a reagent for detecting LRRK2 gene mutation and cfDNA integrity in preparation of a product for early warning or screening high-risk population of Parkinson's disease. According to the early warning and screening method for the high-risk population with the Parkinson's disease, LRRK2 gene mutation detection of nuclear DNA and plasma nuclear cfDNA integrity analysis are combined, and the accuracy and pertinence of early warning and screening of the high-risk population with the Parkinson's disease are improved through a combined screening method; the sensitivity and the specificity of early recognition of high-risk people with the Parkinson's disease are remarkably improved, the limitation that existing clinical diagnosis of the Parkinson's disease mainly depends on medical history inquiry and physical examination is broken through, and the clinical management burden of the high-risk people with the Parkinson's disease carrying LRRK2 gene mutation is reduced.

Methods and compositions for enhancing nuclear DNA delivery are provided. Aspects of the methods include contacting a cell with a DNA to be delivered to the nucleus of the cell and an agent that modulates the activity of protein Barrier-to-Autointegration Factor (BAF) in a cell. In addition, compositions, including reagents, devices and kits thereof, that find use in practicing embodiments of the subject methods are provided.

The invention discloses a snow flea antifreeze protein based on a cell penetrating peptide and application thereof, and belongs to the crossing field of genetic engineering and cell preservation technologies. The fusion protein rTAT-GS-MU obtained by fusing TAT peptide at the N end of rSfAFP-MU through a (G4S) 3 linker and a non-covalent compound of SfAFP-MU and Pep-1 are constructed, the intracellular delivery efficiency of the SfAFP-MU can be remarkably improved, the mitochondrial function of cells can be remarkably improved, and nuclear DNA damage can be reduced (the content of gamma-H2AX is reduced by 140% at most). The invention provides an important basis for developing a high-efficiency and low-toxicity broad-spectrum cell cryopreservation protective agent.

This invention relates to a nuclear-targeted multimodal imaging diagnostic probe with BNCT therapeutic efficacy, its preparation, and its application, belonging to the fields of biomedicine and nuclear medicine technology. This boron drug contains... 10 Using acetylacetone difluoroborate as the parent nucleus, this invention endows the tumor with nuclear targeting ability by introducing N- or S-containing heterocyclic structures, while utilizing its conjugated structure to provide fluorescence / photoacoustic dual-modal imaging functionality. Based on this, the invention achieves three core functions: first, through fluorescence / photoacoustic dual-modal imaging, it enables the visual localization and real-time monitoring of tumor sites; second, by leveraging the binding of nuclear targeting groups to nuclear DNA / RNA, it... 10 B is precisely delivered into the nucleus, significantly improving the killing efficiency of BNCT; thirdly, thermal neutron irradiation is performed under imaging guidance, triggering... 10 The B(n,α)⁷Li nuclear fission reaction ultimately enables high-precision integrated diagnosis and treatment. This invention also discloses a method for preparing this probe, which has promising clinical application prospects.

The invention relates to genetic breeding, in particular to a method for cultivating undaria pinnatifida triploid sporophytes by inducing homozygous diploid gametophytes. The method comprises the following steps: inducing homozygous 2n undaria pinnatifida sporophores to produce homozygous 2n gametophytes through spore-free propagation, and hybridizing the homozygous 2n gametophytes with common haploid (n) gametophytes to obtain undaria pinnatifida triploid (3n) sporophores; and determining the relative content of DNA in the nucleus of the hybrid sporophyte by using a flow cytometer, thereby identifying the ploidy of the chromosome as 3n. The 3n sporophytes are transplanted to the sea for cultivation, and the 3n sporophytes are identified to be incapable of releasing zoospores in the undaria pinnatifida seedling raising (breeding) season, namely infertile. The method can be used for cultivating a new variety of high-yield and high-quality undaria pinnatifida, and has important significance in developing genetic breeding and new variety creation research in undaria pinnatifida and even kelp brown algae.

The present invention relates to a base editing method for plant DNA, the method comprising a step of expressing a base editing composition in a target plant, plant cell or protoplast, the base editing composition comprising one or more DNA binding proteins and one or more zymoproteins, or comprising a polynucleotide encoding said proteins. The invention is used for editing bases in nuclear DNA or organelle DNA of plants, especially for editing bases in organelle DNA of plants such as chloroplast or mitochondria. The base editing composition can be used for realizing targeted editing from adenine (A) base to guanine (G), targeted editing from cytosine (C) base to thymine (T) base or a method for realizing the two editing methods at the same time in plant DNA (Deoxyribose Nucleic Acid). In addition, the present invention relates to a plant cell, plant or seed implementing such base editing.

Methods and compositions for enhancing nuclear DNA delivery are provided. Aspects of the methods include contacting a cell with a DNA to be delivered to the nucleus of the cell and an agent that modulates the activity of protein Barrier-to-Autointegration Factor (BAF) in a cell. In addition, compositions, including reagents, devices and kits thereof, that find use in practicing embodiments of the subject methods are provided.

The invention belongs to the field of biomedical engineering, relates to a human mitochondrial genome detection technology, and provides a human mitochondrial gene mononucleotide mutation detection method which comprises the following steps: extracting whole genome DNA of a sample; carrying out UM I labeling and purification on the mtDNA; carrying out targeted amplification enrichment and purification on the mtDNA connected with the UMI; constructing an mtDNA library; and performing computer sequencing by using a nanopore sequencing technology to obtain sequencing data, and analyzing the sequencing data to obtain a single gene mutation result. According to the method disclosed by the invention, by virtue of UM I library building and Nanopore sequencing technologies, the situation that obtained Nanopore sequencing data contains sequences except mtDNA, such as nuclear DNA, can be avoided, so that an mtDNA mononucleotide mutation result obtained after analysis of the Nanopore sequencing data is not distorted and is closer to a real situation.

The present invention provides a kit, gene chip, and method for detecting DNA methylation levels in a subject's smoking status. The kit includes reagents capable of specifically detecting methylation sites in a biological sample. These methylation sites include nuclear DNA methylation sites and mitochondrial DNA methylation sites. Nuclear DNA methylation sites include cg14021375, cg03561637, cg20736847, cg12810233, cg09167044, and cg04720886; and mitochondrial DNA methylation sites include D-loop, ATP6, ATP8, and MT-COX1. This method addresses the difficulty in accurately determining a subject's smoking status in existing technologies and is suitable for use in the field of smoking status detection.

This invention provides an Auger electron radiotherapy drug that can selectively and effectively release a sufficient amount of Auger electrons into the nuclear DNA of cancer cells, even in small amounts, thereby reducing or killing cancer cells. The Auger electron radioactive isotope has a half-life that is not too short but not too long, making it highly safe and readily available. [Solution] The Auger electron radioactive therapeutic agent is encapsulated in a stimulus-responsive liposome that accumulates in cancer tissue and / or cancer cells, such that an anthracycline derivative is released upon stimulation, in which an Auger electron-emitting radioisotope-substituted benzene ring-containing group or radioisotope-substituted alkyl group is covalently bonded to the keto or amino group of anthracyclines selected from doxorubicin or daunorubicin and their reduced forms or alkoxy group-substituted forms thereof, is a stimulus-responsive liposome, or is bound to an antibody, oligopeptide, or antigen that accumulates in cancer tissue and / or cancer cells via a stimulus-responsive linker.

The invention relates to the technical field of anti-tumor drugs, in particular to a drug targeting exosomal DNA, a preparation method and application of the drug in treating urothelial carcinoma, the drug is an antibody drug conjugate and comprises a bispecific antibody and a cytotoxic drug coupled with the bispecific antibody, the bispecific antibody can be combined with a DNA ligase III and a programmed death ligand 1 at the same time, the DNA ligase III is a nuclear DNA ligase III, an extrachromosomal DNA maintenance mechanism is used as a treatment target for the first time, cyclization and maintenance of extrachromosomal DNA are destroyed by targeting the nuclear DNA ligase III, and the driving effect of oncogene amplification is weakened fundamentally.

The invention discloses a base editor and application thereof, provides a nucleic acid base editor, and particularly relates to a base editor not based on a CRISPR (clustered regularly interspaced short palindromic repeats) technology. The base editor comprises a sequence specific DNA binding protein, a nicking enzyme, an exonuclease and a base specific deaminase. The base editor has single-chain specificity, and compared with a traditional base editor, the base editor has wide applicability in cells and can play a role in cell nuclei and mitochondrial DNA and / or chloroplast DNA. While realizing efficient base editing, the base editor also has the characteristics of high purity of base editing products and few byproducts with insertion and deletion, and is beneficial to being used as an efficient and safe gene editing tool.

The present invention relates to a DNA base editor and a base editing method using a nickase and a zinc finger protein. The present invention is useful for correcting bases in nuclear DNA or organellar DNA and, in particular, for correcting bases in DNA of organelles such as chloroplasts or mitochondria. The DNA base editor according to the present invention has a relatively low molecular weight, and thus can be delivered into an organism while being relatively loosely constrained in terms of vector size. In addition, correction can only occur at a single base within a spacer, thus having the advantage of lowering the possibility of bystander correction.

The invention discloses a sperm nucleus DNA integrity detection kit, and belongs to the technical field of kits.The sperm nucleus DNA integrity detection kit comprises a reagent detection kit, a cover plate is arranged at the center of the upper end face of the reagent detection kit, protection structures are arranged at the centers of the reagent detection kit and the two side walls of the cover plate, and the four protection structures comprise four protection transverse frames; the four protective cross frames are arranged at the centers of the two side walls of the cover plate and the lower portions of the centers of the two side walls of the reagent detection box respectively, first insertion openings are formed in the front and rear portions of the lower ends of the two side walls of the reagent detection box and the front and rear portions of the centers of the two side walls of the cover plate, and first insertion blocks are arranged at the front and rear portions of the centers of the side walls of the four protective cross frames; besides, when the kit is subjected to external collision or extrusion, external force can be effectively dispersed and buffered, the risk that internal parts such as reagent bottles are broken and damaged due to impact is reduced, the stability of products in the transportation and storage process is enhanced, and operation is simpler, more convenient and more reliable.

The invention relates to methods of extracting mitochondrial DNA from whole seeds virtually free of nuclear DNA in a high-throughput environment. Methods also relate to the use of a solid phase nuclear DNA binder to selectively remove nuclear DNA from a sample solution comprising dry seed powder resuspended in an alkaline adsorption buffer and extracting mitochondrial DNA from a supernatant of the sample solution treated with the solid phase nuclear DNA binder. The solid phase nuclear DNA binder comprises Cerium oxide powder or Iron Oxide powder in particular embodiments.

The invention relates to the technical field of biological medicine, and particularly discloses a whole blood free DNA preserving fluid, a vacuum blood collection tube and application, and the preserving fluid is prepared by mixing an anticoagulant, a ribozyme inhibitor, a DNA stabilizer, a metabolic inhibitor, a cell stabilizer and RNase-free pure water. The preservation solution has excellent nuclease inhibition efficiency, and free DNA in plasma can be remarkably protected and is prevented from being degraded; meanwhile, the blood cell structure can be stabilized, blood cell rupture is effectively inhibited, and then nuclear DNA is prevented from being mixed into cfDNA to be detected to cause pollution. Besides, the preservation solution and the vacuum blood collection tube containing the preservation solution can remarkably prolong the stable storage time of the blood sample under the room temperature condition, provide convenience for long-distance transportation of the blood sample, and solve the problem that the prior art cannot give consideration to the structural integrity of blood cells and the detection accuracy of cfDNA. The stability of the blood sample is difficult to maintain for a long time under a normal temperature condition.

A composition comprising: a flavonoid, for example, in an amount of about 0.1 g to about 1.5 g; and one or more of: ascorbic acid, ascorbate, or a combination thereof, for example, in an amount of about 0.2 g to about 2.0 g; N-acetylcysteine, for example, in an amount of about 0.10 g to about 1.2 g; α-lipoic acid, for example, in an amount of about 0.05 g to about 0.60 g; and at least one carotenoid, for example, in an amount of about 1 mg to about 50 mg. The composition can be used to reduce or prevent nuclear DNA damage, mitochondrial DNA damage, lipid peroxidation, protein carbonylation, or any combination thereof in a subject caused by oxidative stress.

Methods and materials for editing DNA (e.g., mitochondrial DNA) are provided herein. For example, chimeric polypeptides containing a nucleic acid interacting domain, a facilitating domain, and a base editing domain are provided herein, as are methods for using chimeric polypeptides to edit mitochondrial or nuclear DNA.

The present disclosure provides methods, compounds, compositions, formulations or medicaments and related uses for treating, preventing, inhibiting, ameliorating or delaying the onset of a mitochondrial disease resulting from nuclear DNA mutations (e.g., mitochondrial DNA (mtDNA) depletion syndrome) in a subject. The methods comprise administering to the subject compounds, compositions, formulations or medicaments disclosed herein to thereby produce the aforementioned therapeutically beneficial effect(s).

This invention discloses a method and system for detecting single-cell apoptosis using nuclear DNA-gated electrochemiluminescence microscopy. The method includes: culturing test cells on a transparent conductive substrate, with the substrate serving as the working electrode, placed in an electrochemical reaction cell; adding a detection solution to the electrochemical reaction cell; the detection system thus constructed utilizes genomic DNA within the cell nucleus as an endogenous biological co-reactant; applying an electrochemical excitation voltage to the working electrode in the detection system to induce an electrochemiluminescence reaction, while simultaneously capturing electrochemiluminescence images of the test cells using a microscopic imaging device; inputting the acquired electrochemiluminescence images into a pre-trained deep learning detection model; the model automatically identifies and outputs the apoptosis state category of each cell based on the electrochemiluminescence images, and statistically outputs the number of cells of each category and their proportion in the total number of cells.

The present invention relates to a method for sequencing a nucleic acid, comprising: providing a sample comprising a nucleic acid; contacting the sample with a DNA-binding molecule comprising a DNA dye; contacting the sample with an insertional enzyme complex to produce labeled nucleic acid fragments, wherein the insertional enzyme complex is inhibited by the DNA-binding molecule; and sequencing the labeled nucleic acid fragments to produce sequence reads; wherein the sample comprises primary nucleic acids and secondary nucleic acids, wherein the primary nucleic acids comprise nuclear DNA and the secondary nucleic acids comprise mitochondrial DNA (mtDNA) or extrachromosomal DNA, and wherein the DNA-binding molecule preferentially binds to secondary nucleic acids over primary nucleic acids.

To provide methods and compositions for restoring STMN2 levels.SOLUTION: TDP-43 is primarily a nuclear DNA / RNA-binding protein with functional roles in transcriptional regulation, splicing, pre-microRNA processing, stress granule formation, and messenger RNA transport and stability. The present invention relates to compositions and methods for treating diseases or conditions associated with TDP pathology or diminished TDP-43 functioning in neural cells of a subject, and for identifying candidate agents that inhibit or prevent the inclusion of defective or altered STMN2RNA sequences.SELECTED DRAWING: None