33 results about "Gene defect" patented technology

The invention belongs to the technical field of biomedical imaging, and particularly discloses an in-vivo imaging method of an SAPAP3 gene defect disease model, which is characterized in that an effective dose of an S1PR1 receptor targeted radioactive probe is injected into the body of the SAPAP3 gene defect disease model. According to the method, an S1PR1 receptor targeting radioactive probe is utilized, the technical bottleneck that in-vivo and dynamic observation of the S1PR1 receptor cannot be achieved through an existing in-vitro technology is solved, and an indispensable visual tool and a quantitative evaluation means are provided for studying the neurobiological mechanism of related mental diseases such as obsessive-compulsive disorder and accelerating research and development of related drugs.

The application discloses application of branched-chain amino acid transaminase 1 gene in treatment of maple syrup urine disease, and relates to the field of gene therapy. Maple syrup urine disease caused by BCAT2 gene defect can be effectively treated by up-regulating branched-chain amino acid transaminase 1 (BCAT1), and it is verified for the first time that overexpression of BCAT1 (cytoplasm type / brain type) can systemically save lethal metabolic phenotypes caused by BCAT2 (mitochondrial type / general type) defects. The application breaks the barrier of metabolic division, and proves that expression of non-mainstream metabolic enzyme (BCAT1) in non-classical metabolic organs (liver) is enough to reconstruct BCAA decomposition flux. The application expands the MSUD treatment target spectrum: from “must repair BCKDC” to “can compensate for upstream limiting steps in ectopia”, and provides alternative strategy reserves for BCKD-deficient MSUD.

The invention relates to the field of gene editing and tumor immunotherapy, and discloses a CEACAM1 gene defect type engineered immune cell as well as a preparation method and application thereof. The engineering immune cell is characterized in that: (i) a CEACAM1 gene is knocked out; (ii) specifically recognizing and killing tumor cells expressing CD19; (iii) expressing CAR (chimeric antigen receptor); and iv) the immune cells are T cells. The CEACAM1 gene knockout CAR-T cell prepared by the invention shows an anti-tumor curative effect superior to that of a control group in malignant tumors of a blood system, has stronger in-vivo amplification capacity and good safety, reverses functional inhibition caused by IFN-I to a certain extent, and shows relatively high clinical application potential.

The present invention provides a pluripotent stem cell into which a nucleic acid encoding a chimeric antigen receptor (CAR) specific to CD5, CD2, or CD6 has been introduced. The present invention also provides a CAR-T cell specific to CD5, CD2, or CD6, which is obtained by inducing the differentiation of the pluripotent stem cell into a T cell, and has the following characteristics: (a) that the expression of CD5, CD2, and CD6 is reduced compared to that of a corresponding CAR-T cell derived from peripheral blood; and (b) that cytotoxic activity against T-cell tumors is higher than that of the corresponding CAR-T cell and a CD5, CD2, or CD6 gene-deficient CAR-T cell, which are derived from peripheral blood.

The present invention relates to: an AAV-based PDE6B viral vector for treating retinitis pigmentosa, the AAV-based PDE6B viral vector containing a tissue-specifically expressed PDE6A promoter; and a use of thereof, and provides a gene therapy for treating retinitis pigmentosa caused by PDE6B gene deficiency. The in vivo therapeutic efficacy of seven types of AAV5-PDE6B vectors was confirmed using an AAV by using a PDE6A promoter that is tissue-specifically expressed in photoreceptor rod cells that develop retinitis pigmentosa. An AAV5-PDE6A-450-PDE6B vector was selected as a candidate due to exhibiting strong tissue-specific expression in photoreceptor rod cells under even off-target conditions, unlike the gene expression characteristics of an AAV5-CMV-PDE6B vector, and was tested so as to be usable in the development of a gene therapeutic agent for treating PDE6B-deficient retinitis pigmentosa patients. Therefore, the present invention, related to AAV5-PDE6B for retinitis pigmentosa treatment and containing a tissue-specifically expressed PDE6A promoter, provides retinitis pigmentosa patients with an important treatment option having improved safety, and can be expected to have fundamental therapeutic effects compared to conventional treatments.

The invention relates to a construction method and application of a spontaneous and persistent ventricular tachycardia animal model, in particular to a spontaneous and persistent ventricular tachycardia rat model based on MYL4 gene defect and myocardial infarction induction. The model is constructed by utilizing the synergistic effect of double pathological factors of MYL4 gene conserved gene defects and acquired myocardial infarction, the induction rate of the model is greater than or equal to 90%, the spontaneous duration time reaches 1-3 min, and the method is obviously superior to an existing construction method for inducing the spontaneous and continuous ventricular tachycardia model. The model can simulate the pathophysiological process of ventricular tachycardia after human MYL4 gene related cardiovascular diseases combined with myocardial infarction, provides general technical support for ventricular arrhythmia pathogenesis research, drug screening and medical instrument research and development, and has wide scientific research and clinical transformation value.

The application discloses a recombinant Escherichia coli for efficiently expressing dsRNA, which is a TG1 strain with gene defects and into which the following plasmids are introduced: a first plasmid comprising a T7 RNA polymerase expression module; and a second plasmid comprising a dsRNA expression module. rnc The application also discloses a method for producing dsRNA, and application of the recombinant Escherichia coli in preparing nucleic acid pesticides. rnc The application provides a new recombinant Escherichia coli with gene defects for producing dsRNA in the field of nucleic acid pesticides. rnc The knockout has no significant influence on the growth rate of the recombinant Escherichia coli, and the recombinant Escherichia coli has great industrial fermentation potential. The recombinant Escherichia coli adopts a double-plasmid expression system, and the dsRNA expression module structure with double T7 terminators is used to improve the expression amount and purity of dsRNA synthesis.

The present invention relates to a method for treating cancer, comprising administering a composition comprising γδ T cells treated with an inhibitor of XBP1 gene expression or an inhibitor of XBP1 protein expression or activity. The γδ T cells, in which the XBP1 gene is deficient or the XBP1 protein activity is inhibited, exhibit enhanced antitumor activity in a tumor microenvironment characterized by endoplasmic reticulum (ER) stress, as compared to unmodified γδ T cells. Accordingly, the modified γδ T cells are effective for use in cancer treatment.

The present invention relates to SURF4 gene-deficient erythroid progenitor cells and a method for differentiating same into erythroid cells. SURF4 gene-deficient cells in which the SURF4 gene has been knocked out of erythroid progenitor cells were found to express erythroid differentiation markers at a higher proportion and undergo erythroid differentiation more rapidly under erythroid differentiation conditions according to the present invention. Accordingly, the present invention provides a method for rapidly differentiating erythrocytes using SURF4 gene-deficient erythroid progenitor cells.

The present invention relates to ERRα gene-deficient erythrocyte progenitor cells and a method for differentiating erythrocytes thereof. It was confirmed that ERRα gene-deficient cells, in which ERRα genes are knocked out in erythrocyte progenitor cells, exhibit a higher expression level of erythrocyte differentiation markers and a more rapid progression of erythrocyte differentiation under erythrocyte differentiation conditions according to the present invention. Accordingly, the present invention provides a method for rapidly differentiating erythrocytes by using ERRα gene-deficient erythrocyte progenitor cells.

The present invention relates to UT2 gene-deficient erythroid progenitor cells and a method for differentiating same into erythrocytes. It was confirmed UT2 gene-deficient cells in which the UT2 gene is knocked out in erythroid progenitor cells exhibit a higher expression ratio of erythroid differentiation markers and more rapid progression of erythroid differentiation under erythroid differentiation conditions according to the present invention, Accordingly, the present invention provides a method capable of rapidly differentiating erythroid cells using UT2 gene-deficient erythroid progenitor cells.

The invention provides a capecitabine prodrug for reducing liver metabolism burden and application thereof, a derivative formed by introducing a masking group R capable of enzymolysis or chemical hydrolysis into 5 '-hydroxyl or N-amino of a capecitabine molecule, and the R is selected from amino-acid ester, phosphate, polyethylene glycol chain or cholic acid conjugation group. The prodrug can be selectively activated in intestinal tracts or tumor tissues through a non-UGT1A1 dependent pathway, and 5-fluorouracil is finally released through metabolism. Due to the characteristic, the competitive inhibition of the prototype capecitabine on liver UGT1A1 enzyme is obviously reduced, and the interference on bilirubin binding and excretion pathways is fundamentally reduced. The pharmaceutical composition disclosed by the invention is suitable for patients with UGT1A1 gene defects or liver insufficiency. While good anti-tumor activity is maintained, the hepatotoxicity is remarkably reduced, the medication safety is improved, and good clinical application prospects are achieved.

The invention provides amycolatopsis mediterranei with gene defects as well as a construction method and application of the amycolatopsis mediterranei. The first aspect of the invention provides a construction method of the amycolatopsis mediterranei with the gene defect, and the construction method comprises the step of knocking out a rifamycin biosynthetic gene cluster in a receptor amycolatopsis mediterranei strain U32 (Cas12a) genome and an integrated plasmid pDZLCas12a containing an FnCas12a coding gene to obtain the amycolatopsis mediterranei with the gene defect. According to the invention, a rifamycin biosynthetic gene cluster in a genome of an amycolatopsis mediterranei strain U32 (Cas12a) and an integrated plasmid pDZLCas12a containing an FnCas12a coding gene are knocked out, so that the amycolatopsis mediterranei with gene defects is constructed, and the amycolatopsis mediterranei can be used as a chassis strain for mining identified or unidentified biosynthetic gene clusters in actinomycetes.

Provided herein are compositions and methods for treating and / or preventing chronic kidney disease (CKD) in a subject harboring a mutation in a terminal complement gene. The disclosed compositions and methods employ an agent capable of modulating, inhibiting, or otherwise affecting the formation and / or activity of the membrane attack complex (MAC), thereby reducing or preventing complement-mediated kidney injury associated with terminal complement gene defects.

The invention relates to the field of biomedicine, and provides an application of a Gram-negative bacterium infection target Kdo in research and development of antibacterial drugs. An authorized antibacterial peptide Ly (PEG)-1 is used as a probe; through computer simulation, affinity determination and gene defect strain identification, the key action target is lipopolysaccharide (LPS) internal core Kdo (3-deoxy-D-mannan-octanone acid), Kdo is used as a key component of bacteria LPS and is a basis for maintaining Gram-negative bacteria cell wall integrity, LPS biosynthesis and biological activity exertion, and the Kdo is used as a key component of bacteria LPS. The deletion or modification can directly cause the loss of LPS function and the reduction of the viability of bacteria. At present, no antibacterial drug aiming at the target spot exists, the problem that in the prior art, no biomolecule capable of targeting Kdo to exert strong antibacterial activity exists is solved, and the biomolecule can be used for developing drugs for diagnosing or treating related diseases.

The invention provides application of ANKRD13A in preparation of drugs and diagnostic reagents for intestinal cancer, relates to the technical field of biomedicine, and is technically characterized by providing application of ANKRD13A as a therapeutic target in preparation of drugs for preventing and / or treating intestinal cancer. Close association between ANKRD13A and occurrence and development of the intestinal cancer is defined through a series of verification experiments. Clinical sample analysis shows that transcript abundance and protein expression level of ANKRD13A in a colon cancer tissue are remarkably lower than those in a normal colon tissue; the cell level verification proves that the mRNA and protein expression of ANKRD13A in the colon cancer cell line is obviously reduced compared with that of a normal colon epithelial cell line; animal experiments show that an Ankrd13a gene-deficient mouse is induced by AOM / DSS, the occurrence rate of colorectal tumors is higher, the number of the tumors is larger, and tumor tissues have medium-high-grade canceration characteristics along with abnormal expression of beta-Catenin, nuclear ectopic, increase of Ki67 positive cells and other malignant pathological expressions. The experimental results jointly prove that expression deletion or down-regulation of ANKRD13A is closely related to occurrence risk increase of intestinal cancer.

Sickle cell disease (SCD) is a single gene disorder characterized by mutant hemoglobin-S (HbS) and chronic intravascular haemolysis. Painful vaso-occlusive crises (VOC) are typical of SCD and often associated to a further rise in hemolysis. VOC is the clinically painful form of vaso-occlusion, that is due to the aggregation of red blood cells in the capillaries and venules. Such event is promoted or aggravated by adhesion of polymorphonuclear neutrophils (PMNs) to red blood cells and the endothelium leading to tissue ischemia, inflammation and imperfect repair. Repeated vaso-occlusion and PMNs interactions with the vascular endothelium are thought to promote microvascular injuries in SCD patients. The inventors tested the effect of pharmacological inhibition of TREM-1 with LR12 peptide in two experimental vaso-occlusive crisis models. Additional validation of TREM-1 involvement in vaso-occlusion was verified using mice with sickle cell disease and Trem-1 gene deficiency. In particular, the inventors showed that TREM-1 inhibition is particular suitable for limiting the severity of vaso-occlusions. The results obtained by the inventors also suggest that plasmatic concentration of sTREM-1 could be a reliable biomarker for predicting vaso-occlusions and / or SCD-associated organ dysfunction and end-organ damage.

The present invention relates to a gene therapy method capable of continuously and efficiently correcting genes, and a gene therapeutic agent using same. The gene therapeutic agent of the present invention is expected to be able to treat genetic diseases including Duchenne muscular dystrophy and cystic fibrosis, and furthermore, to provide therapeutic cues for a wide range of diseases caused by genetic defects.

The invention relates to the technical field of biological medicines, in particular to a wheat peptide with a neuroprotective effect as well as a preparation method and application of the wheat peptide. The invention discloses a wheat peptide with a neuroprotective effect. The amino acid sequence of the wheat peptide is shown as SEQ ID NO: 1. The wheat peptide with the nerve protection effect can penetrate through a blood brain barrier and play a role in protecting nerve cell injury, especially in a gene defect type AD model, the half-life period in vivo is about 6-8 hours, and the wheat peptide has good pharmacokinetic characteristics and excellent biological safety. According to the application of the wheat peptide with the neuroprotective effect in preparation of the neuroprotective medicine, the neuroprotective medicine can prevent and / or relieve neurodegenerative disease related nerve injury, and has the effects of protecting nerve cells, resisting oxidative stress injury and improving cognitive function.

The invention discloses application of an MYRF gene mutation detection method in preparation of a conical artery trunk deformity diagnostic reagent, and relates to the technical field of biology, and the technical key point is that the risk of conical artery trunk deformity of a subject is judged by detecting pathogenic mutation of an MYRF gene in a biological sample of the subject. Studies are developed from the aspects of clinical samples, stem cell levels, animal models and the like, the pathogenic mutation of the MYRF gene in the CTA sample is analyzed by utilizing a high-throughput sequencing technology, and the correlation between the gene mutation and disease occurrence is determined; molecular mechanisms of abnormal regulation axes or signal pathways of downstream target genes and heart development related genes caused by MYRF gene defects are analyzed in stem cell and animal models by using modern molecular biology technologies such as ChIP-Seq and RNA-Seq, and an efficient method is provided for diagnosing conic artery trunk deformity.

This invention belongs to the field of biomedical technology and provides an application of a ferroptosis inhibitor in the treatment of hepatitis. This invention reveals that a GRIM-19 gene defect specifically induces ferroptosis in hepatocytes, rather than other cell death mechanisms such as apoptosis, necrosis, or autophagy. This invention provides a ferroptosis inhibitor with Ferrostatin-1 as the active ingredient, solving the technical problem of insufficient intervention against the ferroptosis mechanism in existing hepatitis treatments. This inhibitor can significantly increase the expression level of GPX4 in liver tissue, effectively clear lipid peroxides, a core toxic product in the ferroptosis process, and block the ferroptosis process; in addition, it can significantly inhibit the activation of the NLRP3 inflammasome and reduce the expression of downstream inflammatory factors, thereby alleviating inflammatory cell infiltration and fibrotic lesions in the liver. This invention is applicable to the treatment of GRIM-19 deficiency-related chronic hepatitis, providing a new strategy for targeted therapy of liver diseases.

The invention relates to the field of gene editing and tumor immunotherapy, and discloses an IFNAR1 gene defect type engineered immune cell as well as a preparation method and application thereof. The engineering immune cell is characterized in that: i) an IFNAR1 gene is knocked out; (ii) automatically secreting IFN beta; and (iii) specifically recognizing and killing tumor cells expressing CD19. The engineered immune cell can specifically recognize and kill tumor cells expressing CD19, and meanwhile, IFN beta is automatically secreted to enhance the killing function on the tumor cells.

This invention relates to the biomedical field and discloses the application of the Ano5 gene as a therapeutic target for osteoporosis. This invention utilizes a previously constructed... Year 5 Gene knockout mouse model, construction Year 5 ‑ / ‑ The +OVX mouse model was used to clearly demonstrate the effects of inhibiting Ano5 on osteoporosis at the imaging, histological, biomechanical, serological, and molecular levels. Further research is needed on the inhibition... Year 5 The effects and molecular mechanisms of osteoporosis development, and using osteoclast ferroptosis as a starting point, reveal... Year 5 The mechanism by which gene defects inhibit bone resorption by promoting ferroptosis provides a theoretical basis for treating osteoporosis by targeting the chloride channel protein ANO5. This will contribute to the development of new targets for chloride channels in the treatment of osteoporosis.

This invention provides a method for constructing a mouse obesity model and its application, relating to the fields of biotechnology and medical animal model technology. This invention is the first to discover and confirm complement. C9 Genetic defects can lead to spontaneous obesity in mice, and based on this, a novel method for constructing an animal model of obesity has been developed. The model constructed using this method exhibits spontaneous obesity even under a normal diet, avoiding the interference of a forced high-fat diet. Under a high-fat diet, the obesity phenotype is accelerated and exacerbated, providing a flexible time window and a stronger phenotype for research. The model constructed using this method can not only be used for obesity research but also extended to the study of its entire spectrum of metabolic complications and the construction of an efficient drug screening platform, possessing significant scientific and commercial value.

The application discloses a gene medicine for treating deafness-dystonia-optic neuropathy syndrome caused by TIMM8A gene defect and application. The medicine core is a modularly designed adeno-associated virus vector system which carries an expression cassette containing a tissue-specific promoter and a human TIMM8A treatment gene. The application realizes precise treatment through local minimally invasive injection according to different symptoms: AAV-Anc80L65-MYO15-TIMM8A is injected into the cochlea to treat sensorineural hearing loss; AAV2 / 4-Brn3b-TIMM8A is injected into the vitreous body of the eyeball to treat optic neuropathy; AAV9-hSyn-TIMM8A is injected into the central lateral ventricle to treat dystonia. Preclinical studies have confirmed that the strategy can efficiently express TIMM8A protein in the corresponding target cells, significantly repair hearing, visual and motor function defects, and correct mitochondrial dysfunction from the pathological mechanism.

Use of dihydrotanshinone I or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating and / or preventing a TREX1 gene defect related self-inflammatory disease. It is found that dihydrotanshinone I can effectively inhibit the activation of the cGAS-STING pathway and inhibit the nuclear entry of IRF3 and P65 in diABZI induced BMDMs cells. Further, it is found that dihydrotanshinone I can significantly alleviate the inflammatory response caused by the deletion of the Trex1 gene in mice ‑ / ‑ significantly inhibit the expression of type I interferon related genes (IFN-beta, ifit1, ifit2, Isg15 and Rsad2) in mouse bone marrow derived BMDMs, and dihydrotanshinone I can significantly alleviate the inflammatory response caused by the deletion of the Trex1 gene in mice ‑ / ‑ inflammatory response caused by the deletion of the TREX1 gene in mice.

The invention provides a method for constructing a mouse obesity model and application, relates to the technical field of biotechnology and medical animal models, and discloses a brand-new method for constructing an obese animal model based on discovery and verification that mouse spontaneous obesity can be caused by complement C9 gene defects for the first time. The model constructed by the method can cause spontaneous obesity under normal diet, so that the interference of forced high-fat diet is avoided; obesity phenotype is accelerated and aggravated under high fat diet, and a flexible time window and stronger phenotype are provided for research. The model constructed by the method not only can be used for obesity research, but also can be extended to research of full-spectrum metabolic complications of the obesity and construction of an efficient drug screening platform, and has great scientific research and commercial values.

This invention belongs to the field of plant genetic engineering technology, specifically involving the OsRAV9 gene, a transcription factor that regulates drought resistance in rice, and its application. A drought-induced expression of the OsRAV9 gene was screened, its nucleotide sequence being shown in SEQ ID NO:1; the protein sequence encoded by this gene is shown in SEQ ID NO:2. Using Agrobacterium-mediated transformation, OsRAV9 overexpressing transgenic lines and CRISPR / Cas9 mutant lines were obtained. Seedling drought stress experiments showed that under drought stress, the accumulation rate of MDA in OsRAV9 gene-deficient plants was accelerated, and sufficient free proline could not be formed. In contrast, OsRAV9 overexpressing plants showed a significant increase in free proline content and a relatively slower accumulation rate of malondialdehyde (MDA) under drought stress, preliminarily indicating that OsRAV9 positively regulates drought resistance in rice seedlings.

The invention discloses a method for constructing an NPPK mouse model based on a CRISPR / Cas9 technology and application of the NPPK mouse model, and belongs to the technical field of genetic engineering and disease model construction. The preparation method comprises the following steps: performing targeted knockout on a mouse Serpina12 gene through a CRISPR / Cas9 gene editing technology to obtain a Serpina12 gene-deficient mouse; an acetone-diethyl ether mixed solution (formed by mixing acetone and diethyl ether according to the volume ratio of 1: 1) and double distilled water are sequentially and externally applied to the skin surface of the Serpina12 gene defect mouse, and the NPPK mouse model is obtained. The method has the characteristics of simplicity and convenience in operation, high efficiency and stable phenotype, and the NPPK mouse model obtained by the method can be used for researching inflammatory keratotic dermatosis and screening drugs for treating NPPK or IL-17 related inflammatory dermatosis.