51 results about "RAD51" patented technology

The present invention relates to treatment of Trop-2 positive cancers with the combination of anti-Trop-2 ADC and a Rad51 inhibitor. Preferably the drug conjugated to the antibody is SN-38, and the ADC is sacituzumab govitecan. The ADC may be administered at a dosage of between 4 mg / kg and 16 mg / kg, preferably 4, 6, 8, 9, 10, 12, or 16 mg / kg. When administered at specified dosages and schedules, the combination of ADC and Rad51 inhibitor can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Surprisingly, the combination is effective to treat cancers that are refractory to or relapsed from irinotecan or topotecan.

Methods of treating cancer using antisense oligonucleotides directed against DNA double-strand break repair proteins such as BRCA2 or RAD51 are provided. The antisense oligonucleotides can be used alone, in tandem or in combination with other cancer therapies, in particular with therapies that lead to DNA damage, inhibition of DNA repair or inhibition of DNA synthesis, such as radiation, platinum drugs, alkylating agents, PARP inhibitors, or inhibitors of thymidylate synthase.

The invention relates to a gene detection kit for prognosing gastric cancer metastasis. The kit comprises a DNA library building kit, wherein the DNA library building kit comprises a high-risk gene probe and a low-risk gene probe; the high-risk gene probe comprises CDH1, CDH2, SNAIL, SLUG, MUC4, MUC6, PRSS3, USP6, MLH1, MSH2, MSH6, PMS2, TGFBR2, MMP2, MMP9, BRCA1, BRCA2, PALB2, ATM, ATR, MUTYH, EMSY, ERCC4, RAD51, PARP1 and XRCC1; the low-risk gene probe comprises ATRX, BRIP1, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, FANCO, FANCP, MDM2, MDM4, MLH1, NPM1, PP2R1A, PRKDC, RAD50, STAG2, XRCC5 and CRCC6. The invention further discloses a use method of the kit. The use method comprises the following steps: extracting cfDNA in a blood sample; building a library for the cfDNA through the DNA library building kit, and then sequencing the DNA to obtain a gene overall length sequence; carrying out gene mutation analysis on the gene overall length sequence.

The invention relates to a kit for predicting colorectal cancer liver metastases and a use method. The kit includes a DNA database building kit, the DNA database building kit comprises probes of a plurality of genes, and the plurality of genes include: high risk genes: KRAS, BRAF, MLH1, NRAS, MSH2, PMS2, UGT1A1, MSH6 AKT1, PIK3CA, PTEN, SMAD4, TP53, NM23, TIAM1, MTS1; and low risk genes: PRKDC, RAD50, STAG2, XRCC5, XRCC6, FANCA, ATR, MUTYH, EMSY, ERCC4, RAD51, PARP1, XRCC1. The kit provided by the invention performs related mutation detection on colorectal cancer liver metastases related genes in peripheral blood, and combines specific scoring mechanism to rapidly and conveniently judge and predict colorectal cancer liver metastases.

The invention relates to application of a compound fangchinoline with a tetrahydroisoquinoline parent nucleus in the aspect of resisting conjunctival melanoma and research on an action mechanism of the compound fangchinoline. Specifically, experiments show that fangchinoline directly targets far-end upstream binding protein 2 (FUBP2), so that gene expression of c-Myc protein is reduced, expression of key proteins RAD51 and BRCA1 of c-Myc downstream homologous recombination (HR) pathways is reduced, and the purpose of inhibiting tumor replication is achieved. The compound disclosed by the invention can be administrated together with cisplatin or olaparib to increase the anti-conjunctival melanoma drug effect and reduce the drug toxicity, so that the compound has a good clinical application prospect.

The structure of a RAD51-BRC repeat sequence complex structure is provided. The structure can be used in modelling the interaction of molecular structures such as potential pharmaceutical compounds. Mutant RAD51 and BRCA2 polypeptides and RAD51-BRC repeat sequence chimaera proteins and are also provided. The mutants may be used in assays for finding compounds which interact with or form part of a RAD51 pathway, and the chimaeras can be used to form crystals which may be analysed by X-ray crystallography.

A double stranded RNA having a specific nucleotide sequence is useful for treating cellular proliferative disorders. The double stranded RNA acts as siRNA against the Rad51 gene. The double stranded RNA of the present invention inhibits cellular proliferation itself. In addition, co-administration of the double stranded RNA with a chemotherapeutic agent further enhances its pharmacological effect. The combined use of the double stranded RNA with an agent having a nucleic acid synthesis-inhibitory activity or a nucleic acid-impairing activity is particularly effective.

In accordance with the objects outlined above, the present invention provides methods of diagnosing individuals at risk for a disease state which results in aberrant Rad51 loci. The methods comprise determining the distribution of Rad51 foci in a first tissue type of a first individual, and then comparing the distribution to the distribution of Rad51 foci from a second normal tissue type from the first individual or a second unaffected individual. A difference in the distributions indicates that the first individual is at risk for a disease state which results in aberrant Rad51 loci. Preferred disease states include cancer and disease states associated with apoptosis.

The invention belongs to the technical field of biology and biochemistry, and relates to a method for specifically capturing RecA (Right External Carotid Artery) mediated homologous target DNA (Deoxyribose Nucleic Acid) fragments in samples. The method comprises the following steps of: performing an in-vitro simulation on an action mode of the RecA in in-vivo homologous recombination; designing homologous probes aiming at the target DNA fragments; and specifically capturing the homologous target DNA fragments in the samples in a reaction system containing the RecA and ATP-Gamma-S through RecA assisting probes and an elution reagent. The method can be used for the capture sequencing of exons or other target fragments. Thus, a technology for detecting the rare mutation sites of tumors and other diseases is improved. By utilizing the method, the problems in the prior art that the uniformity of Tm values of the probes designed for capturing the exons or the other target fragments is required, the specificity is not generated in probe hybridization, the initial quantity of the required samples is relatively large and the like are solved. The method also can be used for capturing in-vivo DNA binding proteins based on the homologous recombination of Rad51 under the state of eukaryotic chromatins.

Disclosed are vectors, kits and methods useful in the construction of recombinant cells and DNAs via enhanced efficiency homologous recombination. The vectors are targeting vectors that contain a gene-of-interest spliced between two ends that are homologous to a genome target site. The ends of the vector may be protected from exonuclease attack by deploying a cap, such as a hair pin structure. The vector is linked to a nuclear localization signal sequence, and preferably, a bait peptide that binds to RAD51, to facilitate homologous recombination. The vector may be deployed in myriad genetic transformation applications, such as site-directed mutagenesis, gene therapy, and the like.

The present invention includes novel RAD51 inhibitors. The compounds of the invention may be useful in preventing or treating cancer in a subject in need thereof. The present invention also includes methods of preventing or treating cancer in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention.

Methods of treating cancer using antisense oligonucleotides directed against DNA double-strand break repair proteins such as BRCA2 or RAD51 are provided. The antisense oligonucleotides can be used alone, in tandem or in combination with other cancer therapies, in particular with therapies that lead to DNA damage, inhibition of DNA repair or inhibition of DNA synthesis, such as radiation, platinum drugs, alkylating agents, PARP inhibitors, or inhibitors of thymidylate synthase.

The invention discloses a construction method of a disease animal model and a fusion protein. The fusion protein comprises a DNA (Deoxyribose Nucleic Acid) binding structural domain of the Rad51, cytosine deaminase APOBEC3A and nuclease. The method comprises the following steps: introducing the fusion protein and sgRNA into animal cells, and carrying out gene editing on a target gene. The invention provides a novel platform for efficiently generating the disease animal model, and the manufacturing process of different animal models is greatly promoted.

Methods of killing or inhibiting the growth cancer cells and tumors and of treating cancer by administering compounds that stimulate the activity of RAD51. Cells overexpressing RAD51 or with other imbalances in homologous recombination machinery are particularly susceptible targets of RAD51 stimulators.

The invention relates to a kit for predicting lung cancer metastasis, and a usage method of the kit. The kit comprises a DNA library kit which comprises probes of multiple genes, and the multiple genes comprise: high-risk genes: BRCA1, BRCA2, PALB2, ATM, ATR, MUTYH, EMSY, ERCC4, RAD51, PARP1 and XRCC1; and low-risk genes: ATRX, BRIP1, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, FANCO, FANCP, MDM2, MDM4, MLH1, NPM1, PP2R1A, PRKDC, RAD50, STAG2, XRCC5, XRCC6. Through performing related mutation detection to the related genes of DNA repair system signal paths, lung cancer metastasis can be rapidly and conveniently judged and predicted by combining a special rating mechanism.

The invention belongs to the technical field of precision medicine, and discloses a medicine for treating advanced refractory solid tumors with TP53 mutation and application. The medicine for treatingthe advanced refractory solid tumors with TP53 mutation comprises apatinib and olaparib. AN anti-angiogenesis medicine is combined with a PARP inhibitor to treat the advanced solid tumors with TP53 mutation, and magical curative effects are achieved. The anti-angiogenesis medicine combined with the PARP inhibitor shows a certain anti-cancer curative effect in preclinical research. The anti-angiogenesis medicine can down-regulate homologous recombination repair related genes such as BRCA and RAD51, can make cells in a hypoxic state, and can enhance the treatment effect of the PARP inhibitor.

The present invention includes novel RAD51 inhibitors. The compounds of the invention may be useful in preventing or treating cancer in a subject in need thereof. The present invention also includes methods of preventing or treating cancer in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention.

Embodiments concern methods and small molecule compositions for selectively inhibiting RAD51-mediated D-loop formation while preserving RAD51's ability to form nucleoprotein filaments. The selective RAD51 D-loop formation activity inhibitors DNA repair while minimizing replication-associated toxicity in normal tissue.

The invention discloses a product used for treating and / or preventing beta hemoglobinopathy and a fusion protein. The fusion protein comprises a DNA binding structural domain of Rad51, a cytosine deaminase APOBEC3A mutant and nuclease, the cytosine deaminase APOBEC3A mutant means that asparagine at the 57th site of cytosine deaminase APOBEC3A is mutated into glycine. The product comprises a coding gene of the fusion protein and a delivery vector of sgRNA, and the sgRNA guides the fusion protein to carry out single-base gene editing on HBG1 and HBG2 promoter regions in target cells. According to the product used for treating and / or preventing the beta hemoglobinopathy and the fusion protein, the single-base gene editing efficiency can be greatly improved, and the HBG1 and HBG2 promoter region-117 sites are more accurately and efficiently targeted to generate G-to-A mutation, so that the expression of gamma-globin is activated, and a more accurate and efficient treatment strategy is provided for clinical treatment of beta-hemoglobinopathy.

The invention relates to the technical field of preparation of medicine for treating echinococcosis, in particular to a composition combining DNA damage causing compounds with DNA damage repair inhibitors, and a preparation method and application of the composition. The composition comprises the DNA damage causing compounds and the DNA damage repair inhibitors. The DNA damage causing compounds areone or more kind of materials of harmine, harmine derivatives, adriamycin, dactinomycin, daunorubicin, etoposide and teniposide; and the DNA damage repair inhibitors are one or more kind of materialsof an RAD51 inhibitor and a BRCA1 inhibitor. Through combined use of the DNA damage causing compounds and the DNA damage repair inhibitors, the composition provided by the invention is used for treating the echinococcosis; the effect of realizing the damage to worm body DNA by the DNA damage causing compounds and realizing the inhibition on the DNA damage repair by the DNA damage repair inhibitors at the same time can be achieved; the worm body DNA damage repair process is completely blocked; finally, the worm body apoptosis is caused; the anti-echinococcosis effect is achieved; and the anti-echinococcosis treatment effect is improved.

Contemplated compounds disrupt interaction between BRCA2 and RAD51, likely by binding to RAD51. Based on the crucial role of the BRCA2-RAD51 complex formation in DNA repair and the role of RAD51 in the control of entry into S-phase from G1, numerous compositions and methods are presented. Among other advantageous uses, contemplated compounds may be employed as protective agents for non-neoplastic cells in chemotherapy before exposure of the cells to a chemotherapeutic drug, and / or as DNA-damage sensitizer for neoplastic cells.

A method comprising co-administering to a subject having cancer, suspected of having cancer, or at risk of developing cancer: a therapeutically effective amount of at least one compound (a) selected from (a)(i) a nitroalkene fatty acid, (a)(ii) an unsaturated fatty acid having an electron withdrawing group, a leaving group, and a carbon-carbon double bond disposed between the electron withdrawing group and the leaving group, (a)(iii) a thiolated nitro fatty acid, or (a)(iv) a dicarboxylic acid compound containing an electron withdrawing group; and a therapeutically effective amount of at least one anti-neoplastic agent (b), wherein the cancer is a cancer with hereditary etiology of defects in DNA repair genes, a cancer with a high rate of spontaneous genomic instability, a cancer that responds well to DNA damaging agent(s), or a cancer that responds well to a combination of DNA damaging agent(s) with immunotherapy.

The present invention relates to treatment of Trop-2 positive cancers with the combination of anti-Trop-2 ADC and a Rad51 inhibitor. Preferably the drug conjugated to the antibody is SN-38, and the ADC is sacituzumab govitecan. The ADC may be administered at a dosage of between 4 mg / kg and 16 mg / kg, preferably 4, 6, 8, 9, 10, 12, or 16 mg / kg. When administered at specified dosages and schedules, the combination of ADC and Rad51 inhibitor can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Surprisingly, the combination is effective to treat cancers that are refractory to or relapsed from irinotecan or topotecan.

Chronic myelogenous leukemia (CML), and in particular imatinib resistant CML is treated using compositions and methods in which a Rad51-inhibitor and a kinase inhibitor are administered. Most preferably, the Rad51 inhibitor comprises an indolyl isoquinoline structure and the kinase inhibitor is a BCR-ABL inhibitor.

The invention relates to a kit for forecasting the drug resistance of gastrointestinal stromal tumor. The kit comprises a Rad51 protein and KU70 protein immunohistochemical detection reagent and a specification. A using method of the kit comprises the steps: firstly, respectively carrying out Rad51 protein and KU70 protein immunohistochemical staining on a normal tissue and a tumor tissue of a patient; then, carrying out pathological sectioning and section reading, and measuring staining strength and staining area; and carrying out immunohistochemical scoring according to a calculating methodrealized by multiplying the staining strength by the staining area, if results are that (tumor tissue Rad51 score / normal tissue Rad51 score) is larger than 1 and (tumor tissue KU70 score / normal tissueKU70 score) is smaller than 1, proving that gastrointestinal stromal tumor cannot generate drug resistance, and if results are that (tumor tissue Rad51 score / normal tissue Rad51 score) is smaller than 1 and (tumor tissue KU70 score / normal tissue KU70 score) is larger than 1, proving that the gastrointestinal stromal tumor can generate drug resistance.

Methods of treating cancer using antisense oligonucleotides directed against DNA double-strand break repair proteins such as BRCA2 or RAD51 are provided. The antisense oligonucleotides can he used alone, in tandem or in combination with other cancer therapies, in particular with therapies that lead to DNA damage, inhibition of DNA repair or inhibition of DNA synthesis, such as radiation, platinum drugs, alkylating agents, PARP inhibitors, or inhibitors of thymidylate synthase.

Methods of treating cancer using antisense based therapies including antisense oligonucleotides of si RNAs directed against DNA double-strand break repair proteins such as BRCA2 or RAD51 are provided. The antisense based therapies can be used alone, in tandem or in combination with other cancer therapies, in particular with therapies that lead to DNA damage, inhibition of DNA repair or inhibition of DNA synthesis, such as radiation, platinum drugs, alkylating agents, PARP inhibitors, or inhibitors of thymidylate synthase.

Methods of treating cancer using antisense based therapies including antisense oligonucleotides of si RNAs directed against DNA double-strand break repair proteins such as BRCA2 or RAD51 are provided. The antisense based therapies can be used alone, in tandem or in combination with other cancer therapies, in particular with therapies that lead to DNA damage, inhibition of DNA repair or inhibition of DNA synthesis, such as radiation, platinum drugs, alkylating agents, PARP inhibitors, or inhibitors of thymidylate synthase.