15 results about "Genomic Stability" patented technology

The invention relates to the technical field of biological medicines, in particular to application of categravir or medicinal salt thereof in preparation of tumor treatment medicines. The applicant discovers that the categravir can enable chromatin of tumor cells to be more open, so that DNA of the tumor cells is more easily attacked by chemotherapeutic drugs, more DNA damage is generated, genome instability is caused, the apoptosis number of the tumor cells is further increased, and the development of tumors is inhibited. The mechanism can reduce the dosage of chemotherapeutic drugs, thereby reducing the non-selective damage of the chemotherapeutic drugs to normal tissues and improving the treatment safety. And a new treatment choice is provided for patients who are ineffective in traditional chemotherapy, and the compound is especially suitable for chromatin accessibility abnormality mediated drug-resistant tumors.

The present disclosure provides methods for assessing and / or treating subjects having CCUS, MN, or AML. In some embodiments, treatment of a subject with TTKi prevents progression of TP53mut CCUS to TP53mut MN. In other embodiments, methods are provided to treat TP53mut MN with a TTKi, which functions by increasing genomic stability, increasing dysfunction of the spindle assembly checkpoint, and decreasing survival of aneuploidy cells. In another embodiment, the subject is treated with a TTKi in combination with at least one additional therapeutic agent, which may include a BCL-2 inhibitor, intensive chemotherapy, and a stem cell transplant.

The present invention discloses a method for establishing a cervical disease progression prediction model based on low-depth whole-genome sequencing technology, which uses cervical scraping or vaginal swabs to collect exfoliated cells, extract DNA, and perform whole-genome sequencing to obtain the original offline data of low-depth whole-genome sequencing of the DNA sample; the above-mentioned original data is subjected to standard quality control, and then compared with the human reference genome sequence and the repetitive sequences are marked; the genome instability index is calculated by the following formula:; In addition, the present invention also relates to a method for constructing a cervical disease prediction model; the present invention is conducive to improving the accuracy and sensitivity of detection, reducing the cost of detection, and improving the accessibility of cervical disease screening and prediction, while contributing to the early diagnosis of cervical disease and the formulation of treatment decisions, and improving the management and treatment effects of patients with cervical disease.

The application belongs to the technical field of genetic engineering and cell modification, and discloses a genetic engineering construction method and application of an anti-aging human mesenchymal stem cell. Based on eliminating R-loop formed in the process of cell aging from the source, relieving the adverse effects of genome instability caused by R-loop, the application develops RNH1 overexpression virus transfection MSC aiming at eliminating cell R-loop. The RNH1 overexpression MSC provided by the application exhibits significant anti-aging activity, has strong environmental adaptability and excellent safety characteristics, can effectively resist harsh in-vivo inflammation and aging microenvironment, and avoid the tumorigenic risk after cell transplantation, and the MSCs with stable anti-aging ability can be applied to significantly improve the curative effect of MSCs infusion in-vivo disease treatment.

A method for single-base editing to repair HBA2 gene mutations and its application, belonging to the field of gene editing technology. This method includes the following steps: contacting a single-base editor and gRNA with the HBA gene sequence to be edited and repaired, so that the codon target cytosine base at CD142 in the HBA gene sequence is deaminated and converted into thymine. This method can accurately edit pathogenic mutation sites, does not produce double-strand breaks, does not affect chromatin conformation and genomic stability; nor does it produce random insertions of large fragment genes in the genome, and has a low impact on oncogene activation or tumor suppressor gene inactivation; it will not produce random insertions / deletions at other sites in the genome; and the expression of the repaired target gene is regulated by all natural HBA2 regulatory elements, having high safety and being more capable of balancing the expression of α / β globin.

The invention provides an endometrial stem cell preparation as well as a preparation method and application thereof, and belongs to the technical field of biological preparations. According to the preparation method of the endometrial stem cell preparation, the safety risk is controlled through an autoserum source, the cell function is optimized in combination with a low-oxygen environment, and a high-stability and low-immune-risk standardized solution is provided for clinical transformation of the endometrial stem cell preparation. Three batches of culture data show that the cell viability is gt; the mesenchymal stem cell culture medium is stable in form and meets the mesenchymal stem cell verification standard. The flow detection verification shows that the positive rate of CD73 / CD90 / CD105 is greater than or equal to 95%, the negative markers such as CD34 / CD45 and the like are less than or equal to 2%, and the high purity is proved; the cell cycle shows that the G0 / G1 period accounts for 74-80%, and the resting state and the genome stability are maintained. After the preparation provided by the invention is stored for a short time or frozen and unfrozen for a long time, the cell morphology and proliferation capacity are not obviously attenuated.

The invention relates to a method for recognizing a G-quadruplex (G4) in a cell by utilizing a G4 fluorescent probe 2-(2-hydroxy-6-methoxy-3-propionyl phenyl) quinazoline-4 (3H)-ketone (HMPQ). The method comprises the following steps: firstly, adding a fluorescent probe 2-(2-hydroxy-6-methoxy-3-propionyl phenyl) quinazoline-4 (3H)-ketone (HMPQ) into a cell; the probe has specific binding affinity to G-quadruplex, and can illuminate the non-standard nucleic acid structures without changing the conformation of the probe. G4 participates in chromatin tissue, gene regulation, and genomic stability, and appears to contribute to the growth and progression of cancer. By utilizing the unique fluorescence mechanism of HMPQ (i.e., excited state intramolecular proton transfer), the method can achieve label-free accurate detection of the G4 structure in the cell nucleus. The invention also relates to an unmarked kit for selectively detecting the G-quadruplex (G4) in the cell.

The invention provides an identification method and system for multi-omics analysis of lung cancer brain metastasis driving genes. The method comprises the following steps: data quality control: acquiring single-cell RNA sequencing data from a public data source, carrying out initial cell screening after standardization processing, removing low-quality data and ensuring the reliability of the data; a batch effect removing algorithm is adopted, technical deviation between batches is eliminated, and data consistency is ensured; the cells are grouped, the cells are divided into different subgroups through dimensionality reduction and clustering analysis, and the heterogeneity and diversity of the cells in the tumor microenvironment are revealed; inferring copy number variation, and inferring genome instability and possible canceration characteristics of the cells by analyzing the copy number variation in the single cell data; performing quasi-time sequence analysis, reconstructing a cell development or transformation process by utilizing the quasi-time sequence analysis, and exploring the change of cell fate in the brain metastasis process of the lung cancer; function enrichment analysis: carrying out function annotation on different cell subgroups, and identifying key pathways and molecular markers related to brain metastasis of lung cancer; and drug sensitivity analysis before and after radiotherapy: analyzing the sensitivity difference of different cell subgroups to drugs before and after radiotherapy, and providing a basis for an individualized treatment scheme.

The invention discloses a macaque skin squamous carcinoma cell line MCSCC14397 and application of the macaque skin squamous carcinoma cell line MCSCC14397. The macaque skin squamous carcinoma cell line is named as macaque skin squamous carcinoma cell line MCSCC14397, and the preservation number of the macaque skin squamous carcinoma cell line is CCTCC (China Center For Type Culture Collection) NO: C2025156. The cell line disclosed by the invention has similar protein expression with primary tumor tissues, has chromosome abnormal karyotype, in-vitro tumor formation capability and stable proliferation characteristics, and simultaneously shows remarkable genome instability (such as high-frequency Cgt, T mutation and structural variation) and inflammation signal activation. The MYO10 gene expression in the cell line is up-regulated and drives DNA damage reaction and inflammatory factor expression, and unique advantages are provided for application of the cell line in skin squamous cell carcinoma mechanism research, drug screening and drug efficacy evaluation. The cell line disclosed by the invention can be used as an effective cell model, can be used for establishing a xenotransplantation animal model, and can provide a research basis for deeply researching the occurrence, development, metastasis mechanism and drug resistance mechanism of human skin squamous cell carcinoma as well as innovative drug development and screening.

The invention belongs to the technical field of gene engineering and cell transformation, and discloses a gene engineering construction method and application of anti-aging human mesenchymal stem cells. On the basis that R-loop formed in the cell aging process is eliminated from the source, the adverse effect of genome instability caused by the R-loop is relieved, and RNH1 overexpression virus transfection MSC for cell R-loop elimination is developed. The RNH1 overexpressed MSCs provided by the invention show remarkable anti-aging activity, also have strong adaptive capacity to environment and excellent safety characteristics, can effectively resist harsh in-vivo inflammation and aging microenvironment, avoids tumorigenic risk after cell transplantation, and has good application prospects. The MSCs with stable anti-aging capability can be subsequently applied to remarkably improving the treatment effect of the MSCs infused into a body for treating diseases.

The invention provides an organic-solvent-free cell cryopreservation and separation integrated method, and belongs to the technical field of crossing of nano materials and biomedicine. According to the method, a non-permeable cryoprotectant is efficiently delivered into target cells through a targeting delivery system mediated by a cell targeting recognition ligand, and organic-solvent-free efficient cryopreservation and high-purity separation of the target cells are synchronously realized by utilizing the survival difference between the target cells and non-target cells in the freezing and thawing cycle process. According to the method, a cryopreservation effect equivalent to that of 10% dimethyl sulfoxide (DMSO) is realized, and the stability of a target cell genome is remarkably improved due to avoidance of the toxicity of the DMSO; meanwhile, the separation purity higher than 95% can be achieved without depending on mechanical separation, and multiple cell damage caused by shear stress in the conventional separation process, ice crystal damage during cryopreservation and cryoprotectant toxicity is effectively avoided.

Presented herein are Synechococcus strains engineered to express the bacterial ethylene-forming enzyme (EFE) that exhibit unstable ethylene production due to toxicity and genomic instability induced by accumulation of the EFE-byproduct guanidine. Co-expression of EFE and Sll1077 significantly enhanced genomic stability and enabled the resulting Synechococcus strain GD-EFE7942 to achieve sustained high-level ethylene production. The engineered strains and methods disclosed herein are useful for guanidine degradation pathways and for ethylene bioproduction in cyanobacteria.

A replicating oncolytic virus vector is provided having a modified Enterovirus genome (e.g., a Poliovirus, Coxsackievirus or Echovirus genome), wherein the modified Enterovirus genome has one or more copies of one or more miRNA target sequences inserted into the UTR region (e.g., via substitution) and / or in-frame within the coding region of the Enterovirus genome. Also provided are compositions and methods for treating cancer (including for example, lung cancer).

The present application relates to the technical field of genetic engineering and cell biology, and particularly relates to a universal human induced pluripotent stem cell, PD-L1 The promoter is inserted into a short enhancer sequence, the short enhancer sequence has the characteristics of enhancing the expression of PD-L1 when being differentiated into dopaminergic neural precursor cells or dopaminergic neuron cells, and the short enhancer sequence is selected from any one of TSE012, TSE026, TSE053, TSE075 and TSE089. The present application also relates to a ready-to-use mDAP / mDA cell and application, has cell type-specific immune escape, only when the cell is differentiated into mDAP / mDA, the expression of immune rejection genes PD-L1 and CTLA4 is started, has little influence on genomic stability, and in-situ activation of gene expression is realized.