153 results about "Mitochondrial RNA" patented technology

The invention discloses an indole-benzothiadiazole derivative as well as a preparation method and application thereof. The general structural formula of the indole-benzothiadiazole derivative provided by the invention is shown in the specification, wherein R is selected from one of methyl piperazinyl, diethylamino, azetidinyl and pyrrolidinyl. The derivative can be specifically combined and fluorescently labeled with mitochondrial RNA in cells, and has good selectivity, high fluorescence signal-to-noise ratio and excellent anti-interference capability in a complex biological system. Meanwhile, the indole-benzothiadiazole derivative provided by the invention is simple in synthetic route, easily available in raw materials, good in stability and convenient to store and use, can be specifically combined with RNA and generate strong fluorescence response, is suitable for real-time detection and imaging of in-vitro and in-vivo mitochondrial RNA, and is an efficient mitochondrial RNA micromolecular fluorescent probe.

The invention discloses an endangered animal identification system and method based on a local comparison algorithm and a related device, and relates to the technical field of endangered animal identification, the system comprises a database which is a domestic database edited by experts, and a visual platform module receives a to-be-detected local mitochondrial DNA sequence of a to-be-detected endangered animal input by a user, the local comparison module adopts a local comparison algorithm to locally compare the to-be-detected local mitochondrial DNA sequence with a plurality of reference local mitochondrial DNA sequences in a database to obtain a local comparison result, and determines species of the to-be-detected endangered animal based on the local comparison result; and the visual platform module also displays the species of the to-be-detected endangered animal and detailed information of the species of the to-be-detected endangered animal. According to the application, the comparison efficiency and the comparison precision of the DNA sequence can be improved, and a domestic database is adopted, so that the data security and reliability are improved.

The invention relates to a primer probe combination and a kit for detecting eDNA of Chinese sturgeons and application of the primer probe combination and the kit. Specific primers and TaqMan probes are designed for a D-loop region of Chinese sturgeon mitochondrial DNA, and efficient specific amplification and absolute quantification of Chinese sturgeon eDNA in an environmental sample are realized by optimizing a reaction system and amplification conditions. Compared with the prior art, the method is simple and convenient to operate, does not need to perform harmful sampling on Chinese sturgeon individuals, is suitable for resource monitoring and protection evaluation in a large-range and dynamic environment, and has high sensitivity, high accuracy and high practical value.

The invention provides a compound for releasing a urine fluorescent biomarker under induction of mitochondrial DNA mutation as well as a preparation method and application of the compound, and belongs to the technical field of medicines. The compound disclosed by the invention is prepared by the following steps: complementarily pairing a hybrid nucleic acid nano-carrier containing single-stranded DNA (Deoxyribose Nucleic Acid), an annular fluorescent reporter molecule and a Cas12a / crRNA compound through bases of DNA or RNA, and then coating polyethyleneimine and hyaluronic acid. A CRISPR / Cas12a system is selected as a converter of tumor specific mitochondrial DNA mutation information and urine fluorescence signals, a nano delivery system which responds to mtDNA single base mutation and is used for tumor progress monitoring and early metastasis warning is designed and synthesized, and the nano delivery system has a good application prospect in tumor progress monitoring and early metastasis sensitive detection.

An Interferon Gamma Inducible Protein 16 (IFI16) mutant gene and its use as a marker for predicting, diagnosing, or prognosticating risk or severity of chronic liver disease is described. As a result of performing genomic analysis on NAFLD and NASH patient groups, it was confirmed that the frequency of IFI16 single-nucleotide variants (SNVs) including rs2276404, rs73021847, rs7532207, and rs6940 was increased, and the expression of the IFI16 mutant gene was increased depending on the disease stage of liver disease. The IFI16 SNV was highly expressed in infiltrating macrophages, playing a role in macrophage-induced inflammatory processes, and the IFI16 variant bound more strongly to dsDNA than wild-type IFI16, exacerbating the impaired mitochondrial DNA-sensing response signaling of the IFI16-PYCARD-CASP1 pathway. Thus, the IFI16 mutant gene may be used for predicting, diagnosing, or prognosticating risk or severity of chronic liver disease.

The invention provides a kit for detecting Leber hereditary optic neuropathy and application, and relates to the technical field of biology. The kit comprises: (1) an alkaline lysis solution for releasing mitochondrial DNA in a blood sample; (2) an RPA isothermal amplification reaction system for amplifying the target sequence, wherein the RPA isothermal amplification reaction system comprises an RPA amplification primer; (3) a CRISPR-Cas12a (Clustered Regularly Interspaced Short Palindromic Repeats / Cas12a) system for carrying out high-specificity cutting on a mutation site, wherein the CRISPR-Cas12a system comprises crRNA (Complementary Ribonucleic Acid); and (4) lateral flow chromatography test paper for realizing visual detection. By simplifying the detection process, the kit greatly improves the accessibility of gene diagnosis, so that the gene screening technology can break through the limitation of traditional equipment and is popularized to a wider application scene, and the development of the gene diagnosis technology in the direction of portability, low cost and high precision is promoted. The innovation not only brings a convenient detection tool for gene mutation screening, but also lays a foundation for future gene therapy and personalized medical treatment.

Embodiments of systems, methods, and compositions provided herein relate to assays for selectively controlling enzymatic reactions. Some embodiments relate to methods of inhibiting, reducing, or eliminating secondary DNA (such as mitochondrial DNA) sequencing reads from open chromatic sequencing, whole genome sequencing, or targeted sequencing.

The present disclosure is in the field of low depth whole genome sequence and genetic sequencing. In particular, method of detecting contamination based on haplotype detection of the mitochondrial DNA.

The application discloses a method, device and storage medium for detecting mitochondrial-derived nuclear genome sequences. The method comprises the following steps: aligning whole genome sequencing data to a mitochondrial reference genome rCRS, retaining the reads aligned to the rCRS, aligning the reads to a reference sequence containing 23 pairs of chromosomes and the rCRS, removing non-unique alignment reads; extracting potential junction reads, clustering the junction reads within a distance of 50 bp according to the alignment positions, locating the coordinates and directions of the integrated mitochondrial DNA fragments, and the nuclear genome integration position; searching for inconsistent alignment read pairs within 100 bp upstream and downstream of a read cluster, and counting the number of the inconsistent alignment read pairs as support information for the existence of non-ref NUMTs. The application utilizes the alignment information of the junction reads, detects the non-ref NUMTs through local assembly and clustering, reduces the false positive rate, can obtain accurate breakpoint and fragment information, is simple to operate, and has low detection cost.

Disclosed is a method for editing mitochondrial DNA (mtDNA) within a cell, which include introducing into the cell (a) a DNA cleaving enzyme targeted to the mtDNA sequence to be deleted; (b) a first DNA binding component targeted to a sequence adjacent to the 5′ end of a mtDNA sequence to be deleted; and (c) a second DNA binding component targeted to a sequence adjacent to the 3′ end of the mtDNA sequence to be deleted, where the DNA cleaving enzyme generates a double stranded break (DSB) within the mtDNA sequence to be deleted or generates a single strand nick on the light strand of the mtDNA sequence to be deleted, and wherein the mtDNA sequence between the target sequence for the first DNA binding component and the target sequence for the second DNA binding component is deleted.

The invention discloses a ruthenium complex for inducing mitochondrial DNA polycondensation to overcome tumor drug resistance, an anti-tumor drug and a preparation method and application of the ruthenium complex and the anti-tumor drug. The ruthenium complex is connected with a triphenylphosphine structure-modified bipyridine diazo-anthracene ligand through an alkyl chain, so that the fat solubility of the complex is improved, and the complex can enter cells more easily; the complex has a mitochondrial enrichment function and can be enriched in mitochondria; the complex induces mitochondrial DNA polycondensation so as to cause cancer cell death; the targeting property on tumor cells is effectively improved; the IC50 of the compound on human non-small cell lung cancer cell strains and cis-platinum drug-resistant strains thereof is far lower than that of cis-platinum, and the compound can be used as an excellent anti-tumor drug. The complex takes a ruthenium-coordinated ruthenium precursor compound as a raw material, and the raw material is economical and easy to obtain; the selectivity of the ruthenium complex can be improved, and the cost is saved.

Single-cell methods are provided for investigating DNA and RNA interactions with regulatory proteins and evaluating the cytotoxicity of immune cells towards target cells, such as tumor cells. The methods utilize droplet microfluidics and imaging-based technology to facilitate the isolation and analysis of protein-bound nucleic acids from individual immune cells or apoptotic tumor cells. The methods utilize fluorescence-activated droplet sorting and are capable of isolating and characterizing mitochondrial DNA from cytotoxic immune cells.

Described herein is a base editing system for correcting mutations G3460A, G11778A, or T14484C in mitochondrial DNA of a patient with Leber hereditary optic neuropathy (LHON) to a normal genotype. Also, described herein is a method for correcting a mutation in the mitochondrial genes of a patient with LHON to a normal genotype using a base editor that recognizes specific sites in the mitochondrial genes of the patient with LHON and has an activity of specifically correcting the adenine base at position 3460 or 11778, or the cytosine base at position 14484, by using a fusion protein or a polynucleotide encoding such a fusion protein. The base editor or nucleotide described herein may correct DNA mutations specific to LHON in a cellular or extracellular in vitro environment. Thus, described herein is also the use of the substance in the prevention or treatment of LHON.

Provided are systems for strand-specific editing of DNA, including mitochondrial DNA in humans. The systems provided herein comprise a nickase and a single-stranded (ss) DNA deaminase each, or together, associated with a double-stranded DNA binding polypeptide such that DNA editing occurs in an editing region. Also provided herein are components of the systems for editing DNA taught herein, and methods of use thereof.

The present invention provides novel isoquinolinone compounds that are inhibitors of mitochondrial RNA polymerase for treating various diseases such as cancer and others associated with metabolic disorders and mitochondnal dysfunction.

Compositions and methods relating to a pharmacological therapy for a human genetic disease, specifically mitochondrial DNA depletion-deletions syndromes, and more specifically, those related to mutations in the GUK1 gene. The pharmacological therapy involves the administration of deoxyguanosine (dG), a purine nucleoside phosphorylase (PNP) inhibitor, including but not limited to forodesine, or both.

A small molecule compound DHN and a preparation method and application thereof relate to the technical field of biological medicine.The compound DHN can induce the opening of a mitochondrial membrane permeability transition pore (mPTP), promote the release of mitochondrial DNA (mtDNA) into the cytoplasm, activate a cGAS-STING signal pathway, cut pyroptosis execution protein GSDME, induce pyroptosis death of melanoma cells, and provide a new target and a lead compound for the treatment of melanoma.

The present invention relates to base editing of mitochondrial DNA. More specifically, the present invention relates to: a method for editing mitochondrial DNA bases by using a mitochondrial targeting sequence (MTS); and a base editing system used in the method. The base editing system comprises a DNA binding protein and a deaminase, or polynucleotides encoding these, and does not include an affinity tag or a polynucleotide encoding same. The present invention is useful for editing mitochondrial DNA bases of animal cells or plant cells.

The application discloses a single-cell mitochondrial whole-genome efficient and specific amplification method. The application provides a single-cell or multi-cell mitochondrial genome DNA high-fidelity amplification method, which comprises the following steps: taking total DNA obtained by lysing a test single cell as a template, using a chimeric primer composed of a 5' end non-template matching common sequence and a 3' end mitochondrial DNA (mtDNA) specific matching sequence, and a primer corresponding to the 5' end non-template matching common sequence of the chimeric primer, and using a high-fidelity DNA polymerase with strand displacement activity to simultaneously amplify several overlapping amplicons which completely cover the single-cell or multi-cell mitochondrial genome DNA. The application avoids various problems in the current single-cell mtDNA in-vitro amplification approach, and is a very reliable mtDNA whole-genome amplification method.

The present invention is generally in the field of synthetic biology, gene therapy and cell therapy. In particular, the present invention relates to synthetic transcription factors comprising a DNA binding domain derived from a mitochondrial DNA binding protein (e.g., MTERF1) and a transcriptional regulatory domain derived from one or more other proteins; nucleic acids or combinations of nucleic acids encoding the synthetic transcription factors of the invention; a DNA construct comprising an MTERF1 binding site and a minimum promoter; a system comprising a synthetic transcription factor of the invention and a DNA construct of the invention; and uses thereof, such as medical uses.

The present invention relates to a base correction system that corrects mitochondrial DNA mutations G3460A, G11778A, or T14484C, which are present in patients with Leber's hereditary optic neuropathy (LHON), to a normal genotype. Specifically, the present invention provides a base editor capable of correcting a mutation site in a mitochondrial gene of an LHON patient to a normal genotype. The present invention also provides a method for correcting a mitochondrial gene mutation using a fusion protein or a polynucleotide encoding such a fusion protein that recognizes a specific site in the mitochondrial gene of an LHON patient and specifically corrects the adenine base at position 3460, the adenine base at position 11778, or the cytosine base at position 14484. The base editor or polynucleotide according to the present invention can be used in cells or in an extracellular test tube environment to correct DNA mutations specifically expressed in LHON, and more preferably, can be used as a gene therapy agent to prevent or treat the disease. Thus, the present invention also provides a use of the substance for preventing or treating Leber's hereditary optic neuropathy.

This invention provides biomimetic nanopharmaceuticals for mitochondrial dysfunction, methods for producing the same, and applications. [Solution] The biomimetic nanodrug comprises an RGD-engineered exosome as a carrier, decalinium chloride modified on the surface of the carrier, and oxaliplatin encapsulated inside the carrier. The biomimetic nanodrug of the present invention (OXA@Exo-RD) protects cargoes that induce mitochondrial dysfunction in the blood circulation process, sequentially increasing the accumulation of mitochondria in the cargoes by targeting them. Cargo 1 (DQA) induces oxidative stress, triggering mitochondrial-mediated apoptosis and mitochondrial dysfunction, while cargo 2 (OXA) disrupts mitochondrial DNA and inhibits the initiation of DNA repair, thereby improving chemotherapy resistance. Both cargoes synergistically overcome CRC drug resistance and inhibit its migration.

The present disclosure provides novel polyamide compounds that are useful as binders of DNA, mitochondrial DNA in particular, and in targeted suppression of gene expression. Also provided are novel polyamide compounds comprising a mitochondrial delivery agent or a fluorescent label as well as mitochondria-targeting capsules comprising a novel polyamide compound. Pharmaceutical compositions comprising the compounds or mitochondria-targeting capsules of the disclosure are also provided, as well as medical uses and methods of treatment including the compounds, mitochondria-targeting capsules and pharmaceutical compositions.

The present application provides tools for rapidly, accurately, and accessibly quantifying endonuclease activity. The system is broadly capable of qualifying enzymatic reagents, detecting chemical inhibitors, and optimizing reaction conditions. Minimal adaptations could further enable use in high-throughput screens for enhancers or inhibitors of specific endonucleases. In this context, the present invention demonstrates the utility of mitochondrial DNA (mtDNA) - which is abundant in plasma as cell-free DNA ("cfDNA") and naturally has minimal methylation - as an endogenous digestion control system in MSRE-dependent methylation assays. While demonstrated in the context of qPCR, the control endogenous digestion control systems of the present invention are broadly applicable to MSRE-dependent methylation assays generally, and particularly to those assays that use a multiplex of MSREs having different recognition sequences.

This application provides a method for constructing single-cell libraries of biomaterials embedded in hydrogels, which can be used for constructing libraries of mitochondrial DNA and / or open chromatin regions and / or 3' transcriptome (RNA).

To simplify a process of determining the total base sequence of mitochondrial DNA by using a highly common primer capable of using a fragmented sample.SOLUTION: According to the present invention, total length sequences of known mitochondrial DNA of a plurality of biological species which belong to a specific biological classification are acquired; conserved regions are extracted by aligning the acquired total length sequences of the mitochondrial DNA; primer candidate sequences are set from base sequences of each of the extracted conserved regions; combinations of the primer candidate sequences with which 3 to 6 types of fragments that cover the total length of the mitochondrial DNA can be obtained, and a desired length can be obtained as the length of an overlapping region with a neighboring fragment, are identified as primer set candidates; and at least one of the primer set candidates is selected as the primer set.SELECTED DRAWING: Figure 2

Provided herein are methods, compositions, systems, kits and uses for integrated, simultaneous spatial multiomic analyses of tissues and samples including chromatin accessibility epigenomic analysis, RNA expression transcriptomic analysis, cell cluster and cell lineage analysis, transcription factor motif analysis, extrachromosomal DNA analysis and mitochondrial DNA analysis.

Disclosed herein are engineered meganucleases engineered to recognize and cleave a recognition sequence present in human mitochondrial DNA (mtDNA). The disclosure further relates to the use of such engineered meganucleases in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells, wherein mutant mtDNA is modified or degraded.

It is provided a method of determining the risk of developing Alzheimer's disease dementia in a subject, comprising: (a) determining in a sample of the subject comprising mitochondrial DNA, the methylation pattern in the D-loop region, and / or in the ND1 gene of the mitochondrial DNA; and (b) combining the methylation pattern of one or more sites determined in step (a), with at least one clinical variable of the subject, wherein said combining is performed using a classification model for determining a risk score which correlates to the risk of developing Alzheimer's disease dementia in the subject. A classification model, oligonucleotides, and kits to perform the method, are also provided.