221 results about "DNA Damage Repair" patented technology

The invention discloses a nano system for tumor radioimmunotherapy and a preparation method and application thereof, and belongs to the technical field of biological medicines.The system modifies bacteria outer membrane vesicles (OMVs) through engineering to enable the bacteria outer membrane vesicles to carry magnetite nanoparticles (Fe3O4NPs) and an ATR inhibitor VE822, the Fenton reaction activity of the Fe3O4NPs and the synergistic effect of the ATR inhibitor for inhibiting DNA damage repair are utilized, and the tumor radioimmunotherapy effect is improved. DNA damage is amplified, DNA damage reaction (DDR) is inhibited, generation of hydroxyl radicals (. OH) under radiation is enhanced, radiation resistance of tumor cells is reduced, immune reaction is reactivated, infiltration of effector T cells to tumors is improved, growth of mice tumors is remarkably inhibited, and an effective strategy is provided for tumor radioimmunotherapy.

The invention belongs to the field of daily chemicals, and provides a composition with a longevity gene activation effect, a product containing the composition and application of the composition, and the composition provided by the invention comprises hexapeptide, chlamydomonas and cornflower extract. The hexapeptide, the chlamydomonas nivalis and the cornflower extract are compounded for use, so that the expression of longevity genes KLOTHO and SIRT1 can be remarkably improved. Once the longevity gene serving as the upstream of a signal regulation pathway is activated, various downstream signal pathways can be regulated, such as inhibition of expression of inflammation-related genes, promotion of DNA repair, telomere homeostasis, gene expression of mitochondrial energy and the like, promotion of synthesis of collagen and the like, and finally, longevity of cells and improvement of skin phenotypes are promoted. The effects of resisting wrinkles, tightening and the like are achieved. Therefore, the composition provided by the invention can activate long-life gene expression and regulate and control multiple signal pathways, has potential effects of improving light aging, tightening and resisting wrinkles and the like, and is an anti-aging composition with great potential.

The present application relates to novel compounds described herein, the method of preparing the same, its pharmaceutical composition and method for use thereof. In particular, the invention relates to compounds of formula (I) or their pharmaceutically acceptable salts thereof as inhibitors of ubiquitin-specific protease 1 (USP1) protein and useful in treatment, prevention and / or amelioration of diseases or disorders associated with ubiquitin-specific protease 1 (USP1) including Cancer.

The invention discloses a metal polyphenol network modified drug-loaded radioactive microsphere as well as a preparation method and application thereof, radionuclides are labeled on different microspheres by a precipitation method or an adsorption method, and the metal polyphenol network is modified on the surface of the radioactive microsphere to improve the nuclide labeling stability and the synchronous drug loading capability of the radioactive microsphere. Subsequently, medicine molecules can be adsorbed to the modified radioactive microspheres to obtain the metal polyphenol network modified medicine-carrying radioactive microspheres. The metal polyphenol network modified drug-loaded radioactive microspheres prepared by the invention can solve the problems of radionuclide non-target shedding and DNA damage repair caused by nuclear drugs, avoid secondary drug administration, ensure that drugs directly and accurately reach tumor targets, and improve the drug delivery efficiency. And the selective internal irradiation therapy based on radioactive microsphere mediation is further promoted to play a more effective tumor treatment effect.

The present disclosure provides methods to treat conditions, including cancer, using compounds that can target resistant cancer cells. The compounds can be used to sensitize resistant cancer cells or decrease the proliferation of cells. The compounds can target proteins in the DNA damage repair pathway leading to a decrease in DNA damage repair in target cells.

The present specification relates to a composition for skin protection, which comprises, as an active ingredient, thymol 3, 4, 5-trimethoxycinnamate (3, 4, 5-Trimethoxycinnate Thymol Ester), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof. The composition according to the present disclosure improves the expression of a DNA repair-related gene in skin cells that are photo-aged by ultraviolet light, thereby being capable of inhibiting or preventing skin damage caused by ultraviolet light or external environment or oxidative stress.

The invention discloses an alpha nuclide drug in-vitro cellular response prediction method and system based on multi-module mathematical modeling and a medium, and the method comprises the steps: constructing a basic parameter input module, a pharmacokinetic prediction module, a cell absorbed dose calculation module and a biological effect prediction module which are connected in sequence; a three-compartment dynamical model and a micro-dose learning point kernel convolution and DNA damage repair dynamical model are integrated, and full-chain and quantitative simulation from drug distribution, microscopic energy deposition to cell survival is achieved. The method overcomes the defects that an existing empirical model cannot accurately reflect the high LET characteristic of alpha particles, neglects the bystander effect and repair dynamics and the like, and the prediction precision is remarkably improved. According to the method, the curative effects of different drugs, cell lines and dosage schemes can be quickly simulated on a computer, the research and development cost and period are greatly reduced, and an efficient theoretical tool is provided for new drug screening and dosage optimization.

The invention belongs to the field of biological medicine, and particularly relates to phase separation polypeptide and a preparation method and application thereof. The structure of the phase separation polypeptide is shown as a formula (I). According to the polypeptide compound provided by the invention, liquid-liquid phase separation can be carried out to form condensed liquid drops, and DNA damage response proteins are enriched and separated in cells. The polypeptide compound disclosed by the invention is simple in synthesis method and good in biocompatibility, and liquid-liquid phase separation can be carried out; dNA damage response protein can be captured in cells, DNA repair is interfered, and the tumor radiotherapy effect is enhanced. Therefore, the polypeptide compound provided by the invention can be used for tumor radiotherapy, chemotherapy and other treatment methods.

A circadian rhythm-based time-sharing repair formula and use thereof. A day composition focuses on anti-oxidation, stress resistance and energy metabolism to resist oxidative damage and enhance day vitality and provide long-lasting antioxidation protection. A night composition focuses on DNA repair, anti-inflammation and nerve relaxation to promote cell regeneration and repair and continuously support night repair. The composition of the day composition and the night composition designed according to the circadian rhythm of human metabolism causes the corresponding activities to take effect at the best time, and components are designed to cooperate with each other according to different physiological needs during the day / night, which can greatly improve the anti-aging effect.

The invention discloses a method for site-specific replacement or insertion of DNA fragments in a plant genome, and belongs to the technical field of biology. The method disclosed by the invention comprises the following steps: editing a genome of a plant protoplast by adopting a CRISPR / Cas9 system and taking a double-stranded DNA repair template as a donor template to obtain an edited protoplast; and carrying out culture regeneration on the edited protoplast by utilizing a plant protoplast transformation method to obtain a site-directed mutagenesis plant in the genome so as to realize site-directed mutagenesis of the target plant genome. The method disclosed by the invention can be used for accurately replacing DNA in a plant genome at a fixed point. According to the invention, a recognition sequence of recombinase can be accurately inserted into a genome at a fixed point through homologous recombination, and then accurate fixed-point replacement of a gene large fragment is realized by virtue of a specific recombinase system.

The invention relates to a small molecular boron-10 carrying agent, a preparation method and application. The structural formula of the small molecule boron-10 carrying agent is shown as a formula (I). The invention also provides a preparation method of the small molecular boron-10 carrying agent, which comprises the following steps: carrying out condensation connection on a phenylboronic acid derivative and N-(2-aminoethyl) maleimide hydrochloride, and covalently coupling a boron drug to obtain a first intermediate; n < 2 >-(((9H-fluorene-9-yl) methoxy) carbonyl)-N < 6 >-(tert-butoxycarbonyl)-L-lysine, N-(2-aminoethyl) maleimide hydrochloride and a phenylboronic acid derivative are subjected to condensation connection, and a second intermediate is obtained; carrying out esterification connection on a selenium-containing compound and a DNA repair inhibiting compound to obtain a third intermediate; and carrying out condensation connection on the second intermediate and the third intermediate, and connecting the first intermediate to obtain the small molecule boron-10 carrying agent. The invention solves the problems of limited treatment effect and difficulty in inhibiting DNA damage repair in the existing BNCT. # imgabs0 # (I)

Disclosed herein is Differential Subclone Eradication and Resistance Analysis (DSER), a method developed to identify molecular targets for improved therapy by direct comparison of genomic features of eradicated and resistant subclones in pre-and post-treatment samples from a patient with BRCA2-deficient metastatic prostate cancer. FANCI and EYA4 were identified as candidate DNA repair-related targets for converting subclones from resistant to eradicable, and RNAi-mediated depletion of FANCI confirmed it as a potential target. The EYA4 alteration was associated with adjacent L1 transposon insertion during cancer evolution upon treatment. L1 activation was inhibited by the antiretroviral drug azidothymidine. In conclusion DSER provides an informative intermediate step toward effective precision cancer medicine, especially in cases with dramatic but temporary metastatic tumor regression. L1 transposon activation may be a modifiable source of cancer genomic heterogeneity, suggesting the potential of leveraging newly discovered triggers and blockers of L1 activity to overcome therapy resistance.

The invention discloses miR-150-3p-loaded engineered extracellular vesicles with the surfaces modified with iRGD targeting peptides and application of the miR-150-3p-loaded engineered extracellular vesicles in melanoma treatment, and belongs to the technical field of biological medicines.The miR-150-3p is loaded in EVs, the surfaces of the miR-150-3p are modified with the iRGD targeting peptides, and iEV-150 is obtained; the preparation method of the iEV-150 comprises the following steps: S1, screening miR-150-3p; s2, constructing an HEK293T cell line capable of stably expressing the miR-150-3p; s3, introducing an ANXA2 protein; s4, culturing an HEK293T cell line; s5, separating the EVs; s6, coupling the iRGD targeting peptide to the surface of the extracellular vesicle membrane; the iEV-150 can effectively deliver miR-150-3p to melanoma cells, inhibit tumor cell proliferation, DNA damage repair and epithelial-mesenchymal transition, and promote melanoma cell death by inducing ferroptosis.

The invention discloses an application of a composition of a polypeptide and a PARP inhibitor in preparation of a medicine for treating breast cancer, the sequence of the polypeptide is as shown in SEQ ID NO: 1, and the PARP inhibitor is Olaparil or taprazopalil. The polypeptide can down-regulate the expression of the DNA damage repair gene FANCD2 protein and block the cross-linking damage repair between DNA chains. The PARP inhibitor blocks DNA single-stranded fracture damage repair by inhibiting the catalytic activity of PARP, and is mainly used for breast cancer treatment of BRCA mutation. DNA damage caused by the polypeptide and the PARP inhibitor in two different modes jointly destroys a cell replication fork protection mechanism, so that a DNA replication fork of a breast cancer cell is prone to stagnation and collapse, and cell death is caused. The invention shows synergistic cancer suppression activity in both 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 discloses a heterocycloalkyl carboxylic acid compound, an intermediate and a preparation method and application thereof, and relates to the technical field of medicinal chemistry. The imidazolone compound provided by the invention has a structure as shown in a formula I or a formula II, and in-vitro activity experiments prove that the imidazolone compound has good DNA damage repair and can be used for treating various diseases. # imgabs0 #

The invention discloses a streptomyces mini-gene editing system based on coupled TnpB and reconstructed NHEJ as well as a construction method and application of the streptomyces mini-gene editing system. The system comprises TnpB nuclease which can be expressed in prokaryotic microorganisms through codon optimization, a reRNA guide box of the TnpB nuclease, and a LigD gene expression box, the prokaryotic microorganism itself does not have NHEJ or has a defective NHEJ pathway (such as streptomyces); the reRNA guide box is used for guiding TnpB protein to move towards a target sequence; and the LigD gene expression cassette is used for expressing ligase LigD and reconstructing the prokaryotic microorganism DNA repair system NHEJ. According to the system disclosed by the invention, small InDels can be efficiently introduced near a target site under the action of a reconstructed streptomyces repair system, so that editing of a target gene is realized, and a gene large fragment deletion phenomenon introduced by self-defect repair is avoided.

The disclosure provides methods for treating a cancer, in particular, a DNA damage repair deficient (DDRD) cancer, in a subject comprising administering to the subject an inhibitor of DHX9. In particular embodiments the disclosure provides methods for treating a homologous recombination repair deficient (HRD) cancer, e.g., a BRCA loss of function cancer, in a subject comprising administering an inhibitor of DHX9.

The invention provides a lipid nanoparticle for the targeted combined delivery of a CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR-Cas9) system and a single-stranded DNA (deoxyribonucleic acid) repair template of the liver, and the lipid nanoparticle is prepared from an ionizable lipid ALC-0315, a PC (polycarbonate) lipid DOPC (dioctyl-phthalate), cholesterol and DMG-PEG (dimethyl glycol-polyethylene glycol) (2000) according to a molar ratio of 50: 10: 38.5: 1.5. The lipid nanoparticles can simultaneously package Cas9 mRNA (messenger ribonucleic acid), sgRNA (small guide ribonucleic acid) and a single-stranded DNA (deoxyribonucleic acid) repair template required by homologous directional repair (HDR) gene editing according to a certain proportion to prepare All-in-one LNP. According to the All-in-one LNP, the three nucleic acids are successfully delivered in a liver-targeted combined manner, HDR editing is successfully performed on the liver of a young rat, and an accurate and efficient tool is provided for in-vivo editing.

A drug combination composition comprising ACT001 has a synergistic anti-tumor effect in a glioblastoma (GBM) animal model, effectively protects or improves, in the process of a phase II clinical trial of treating a GBM patient who was sensitive to temozolomide (TMZ) but subsequently relapses, basic immune functions of said patient, such as relieving lymphocyte reduction caused by chemotherapy, alleviating myelosuppression of TMZ, and suppressing inhibitory Treg lymphocytes in peripheral blood, and reduces DNA damage repair capability in GBM cancer cells, thereby improving the sensitivity of GBM to TMZ.

The invention relates to an iRGD modified dual drug-loading liposome and an application of the iRGD modified dual drug-loading liposome in radiotherapy sensitization of targeted glioblastoma. The liposome is composed of HSPC, CHO-HP, DSPE-mPEG2000, and DSPE-PEG2000-MAL, and is loaded with Osimertinib (Osimertinib) and Bortezomib (Bortezomib) through a pH (Potential of Hydrogen) gradient method, and the preparation method of the liposome comprises the following steps: carrying out a reaction on the Osimertinib (Osimertinib) and the Bortezomib (Bortezomib) in the presence of a Osimertinib is used as an EGFR inhibitor, bortezomib is used as a proteasome inhibitor, and osimertinib and bortezomib synergistically enhance the radiotherapy sensitivity by weakening the DNA repair capability of tumor cells. The iRGD peptide on the surface of the liposome is combined with tumor cell specific receptors alpha v beta 3 and NRP1 in a targeting manner, so that the liposome is mediated to pass through tumor neovascularization and efficiently deliver drugs to tumor parts. Animal experiment results show that the enrichment of the liposome in tumor tissues is obviously higher than that of common liposome, and the drug release has good controllability. Compared with the prior art, the invention has obvious advantages in tumor targeting, drug delivery efficiency and radiotherapy sensitization effect, is suitable for combined treatment of radiotherapy drug-resistant glioblastoma, and has a wide clinical application prospect.

The invention provides a cosmetic application of nervonic acid. The cosmetic application is selected from the group consisting of anti-saccharification, energy metabolism, DNA damage repair, soothing and / or repair efficacy. The invention also relates to application of nervonic acid in preparation of an external skin preparation with anti-saccharification, energy metabolism, DNA damage repair, soothing and / or repair effects.

The invention provides methods of determining whether a tumour has a high or low likelihood of being PRR-deficient, based on the values of a plurality of mutational signature metrics for a DNA sample from the tumour. The plurality of mutational signature metrics comprises: the number of indels or proportion of indels in the sample associated with one or more indel signatures of post- replication repair (PRR)-deficiency; and the number of single base substitutions (SBS) or proportion of SBS in the sample associated with one or more SBS signatures of post-replication repair (PRR)-deficiency. A sample that has a high likelihood of being PRR-deficient has a high likelihood of having mismatch repair deficiency (MMRd), polymerase dysfunction (pol-dys), or combined mismatch repair deficiency and polymerase dysfunction (MMRd / pol-dys). Related methods, systems and products are also described.

The invention provides a marker for diagnosing and treating radiodermatitis and application of the marker. The relation between SENP5 and radiodermatitis is researched for the first time, it is found that SENP5 is in positive correlation with occurrence and development of radiodermatitis, an SENP5 overexpression group shows better radiation resistance, skin cells are protected, and damage caused by radiation is relieved. The SENP5 is mainly used for promoting DNA damage repair by mediating an HR repair pathway. Besides, the SENP5 knocked-down cell line is successfully constructed by designing shRNA for specifically knocking down the SENP5 expression level, and it is proved that after SENP5 knocked-down skin cells are irradiated by 60Co rays, the cell survival level is lowered, the homologous recombination repair pathway is obviously inhibited, the NF-kappa B pathway is obviously activated, and the inflammation level is improved. Therefore, SENP5 is represented as an anti-radiation gene in skin cells, and SENP5 can be used as a biomarker of radiodermatitis for early diagnosis of radiodermatitis and targeted preparation of drugs for radiodermatitis.

The present invention discloses a plasmid vector and cell line that can induce targeted genomic DNA double-strand breaks. The present invention constructs a nuclease AscI expression plasmid based on a lentiviral vector backbone by integrating the Tet-on chemically inducible transcription control system and the ERT2 ligand-dependent nuclear localization control system. The vector regulates the transcription of AscI through the Tet-on system and uses the 4-hydroxytamoxifen-induced ERT2 system to achieve spatiotemporal specific nuclear translocation of the endonuclease AscI. The present invention also constructs and screens a cell line that stably expresses AscI. With the help of small chemical molecules, the spatiotemporal expression of the AscI endonuclease in cells can be precisely regulated, thereby inducing DNA double-strand breaks at specific sites in the genome. The present invention provides an efficient and accurate research tool for the field of DNA damage repair, which can be widely used in studying DNA damage repair mechanisms and high-throughput screening of related drugs.

This invention belongs to the field of biomedical technology, specifically relating to the application of DNA damage response gene-related SNPs in the treatment and prognosis of acute myeloid leukemia (AML). This invention is the first to discover that single nucleotide polymorphisms (SNPs) in the DNA damage response pathway (focusing on three major functional modules: damage sensing, signal transduction, and DNA repair) are closely related to the clinical characteristics, treatment response, and survival prognosis of AML. This lays the foundation for constructing a multi-gene risk model based on the DNA damage response pathway and provides theoretical support for integrating germline SNP maps into precision medicine strategies for AML.

The invention discloses application of an umbilical cord blood exosome in preparation of a medicine for treating ophthalmic diseases caused by aging. It is found that the umbilical cord blood exosome can improve the biological characteristics of senescent trabecular meshwork cells, relieve the senescence characteristics of the trabecular meshwork cells, improve the DNA damage repair capacity of the cells, promote proliferation of the trabecular meshwork cells and effectively maintain the stability of cell nucleuses, and then growth and division of the cells are supported. The umbilical cord blood exosome shows a remarkable anti-aging effect in treatment of ophthalmic diseases caused by aging, can effectively improve the biological function of trabecular meshwork cells, slow down the aging process and promote cell proliferation and repair, and has wide application potential.

A method of selecting a treatment for a subject having cancer is disclosed. The method comprises:(a) determining a level of catalytic activity of at least one DNA repair enzyme in a biological sample of the subject; and(b) selecting an immune checkpoint regulator as a treatment for a subject having a statistically significant different level of catalytic activity of the DNA repair enzyme as compared to the catalytic activity of the DNA repair enzyme in a biological sample of a healthy subject.

The present invention provides the afatinib or a pharmaceutically salt thereof for use in the treatment and / or prevention of a cancer in a patient suffering from a disease caused by a defect in DNA damage repair mechanism. Surprisingly, when afatinib was administered to FA cells, it was confirmed that there was a therapeutic anti-cancer effect without any toxic side-effect on DNA.

This invention discloses a method for repairing DNA damage in FFPE samples, comprising: S1. subjecting FFPE sample DNA to heat denaturation; S2. allowing the DNA to fully renature by slow cooling or ice bath; S3. using random primers to bind to large nicked regions of the DNA fragment; S4. adding a mixed repair enzyme to repair the DNA damage; S5. ligating the DNA repaired in step S4 to obtain large DNA fragments, which are then purified with magnetic beads to obtain the repaired DNA. By using random primer single-strand extension to assist the enzyme reaction system, the efficiency of DNA damage / deletion repair is improved; by using random ligation to assemble fragmented DNA into large DNA fragments, the problem of ineffective amplification caused by excessive DNA fragmentation is solved, without affecting the microarray detection results. The entire DNA repair reaction is performed continuously, without the need for multiple purification operations. Compared with other DNA repair methods, it is simple to operate and low in cost, significantly improving the quality of FFPE sample DNA and increasing its detection pass rate in Infinium CytoSNP-850K whole genome microarray detection.

Methods, systems, and software are provided for determining a homologous recombination pathway status of a cancer in a test subject, e.g., to improve cancer treatment predictions and outcomes. In some embodiments, classifiers using one or more of (i) a heterozygosity status for DNA damage repair genes in a cancerous tissue, (ii) a measure of the loss of heterozygosity across the genome of the cancerous tissue, (iii) a measure of variant alleles detected in a second plurality of DNA damage repair genes in the genome of the cancerous tissue, (iv) a measure of variant alleles detected in the second plurality of DNA damage repair genes in the genome of a non-cancerous tissue, and (v) tumor sample purity are provided.