52 results about "Gene defect" patented technology

The invention discloses an Escherichia coli recombinant bacterium capable of efficiently expressing dsRNA, the Escherichia coli recombinant bacterium is an rnc gene defect type TG1 strain, and the following plasmids are transferred: a first plasmid comprising a T7 RNA polymerase expression module, a second plasmid comprising a dsRNA polymerase expression module, a third plasmid comprising a dsRNA polymerase expression module, and a fourth plasmid comprising a dsRNA polymerase expression module; and a second plasmid comprising a dsRNA expression module. The invention also discloses a method for producing the dsRNA. The invention also discloses an application of the recombinant escherichia coli in preparation of nucleic acid pesticides. The invention provides a novel rnc gene defect type escherichia coli recombinant bacterium for dsRNA production in the field of nucleic acid pesticides. The rnc knockout of the strain has no obvious influence on the growth rate of the strain, and the strain has great industrial fermentation potential. According to the recombinant bacterium, a double-plasmid expression system is adopted, and meanwhile, the dsRNA expression module structure of double T7 terminators is utilized to optimize and improve the expression quantity and purity of dsRNA synthesis.

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 conjugate for transferring an effector molecule from outside a cell into said cell, the conjugate comprising at least one effector molecule to be transferred into the cell, at least one saponin of the mono-desmosidic triterpene glycoside type or the bi-desmosidic triterpene glycoside type, and at least one single-domain antibody (sdAb), covalently bound to each other, wherein the sdAb is capable of binding to a cell-surface molecule of said cell. The invention also relates to a pharmaceutical composition comprising the conjugate of the invention. Furthermore, the invention relates to a pharmaceutical composition of the invention, for use as a medicament. In addition, the invention relates to a pharmaceutical composition of the invention, for use in the treatment or the prophylaxis of any one or more of: a cancer, an auto-immune disease such as rheumatoid arthritis, an enzyme deficiency, a disease related to an enzyme deficiency, a gene defect, a disease relating to a gene defect, an infection such as a viral infection, hypercholesterolemia, primary hyperoxaluria, haemophilia A, haemophilia B, alpha-1 antitrypsin related liver disease, acute hepatic porphyria, an amyloidosis and transthyretin-mediated amyloidosis. The invention also relates to an in vitro or ex vivo method for transferring the conjugate from outside a cell to inside said cell or for transferring the effector molecule comprised by the conjugate of the invention from outside a cell to inside said cell, preferably to the cytosol of said cell.

The invention discloses a preparation method of pichia pastoris expression secreting type deglycosylation alkaline phosphatase, and belongs to the technical field of biological engineering. According to the invention, the GS115-BIAP II pichia pastoris genetically engineered bacterium capable of secreting and expressing bovine intestine alkaline phosphatase BIAP II is prepared by using a conventional method. The method comprises the following steps: carrying out site-directed knockout on an ALG3 gene for coding alpha-1, 3-mannosyl transferase and an OCH1 gene for coding alpha-1, 6-mannosyl transferase by using a CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-associated Protein 9) technology to prepare a glycosylation gene defect type engineering bacterium GS115-delta ALG3-delta OCH1-BIAP II. The secretory expression BIAP II is deglycosylated alkaline phosphatase, and the specific activity of the secretory expression BIAP II is close to that of natural BIAP II. The deglycosylated alkaline phosphatase can improve the antibody coupling efficiency and marking uniformity under specific conditions. The method has remarkable advantages in chemiluminescence diagnosis, high-sensitivity immunodetection and development of multifunctional biological coupling reagents.

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 invention relates to a gene delivery vector, a gene delivery system and a preparation method and application thereof. The gene delivery system provided by the invention comprises the gene delivery carrier provided by the invention and lipid nanoparticles; the lipid nanoparticles encapsulate the gene delivery vector. In the prior art, related researches on treatment of metabolic disorder diseases or diseases (such as OTCD) based on lipid nanoparticle LNP delivery are not found temporarily, so that the carrier containing the OTC-circRNA drug gene based on LNP delivery is constructed for the first time, and the carrier can be used for treating the metabolic disorder diseases or diseases. The effectiveness and safety of treatment are researched in vivo and in vitro, a new scheme is provided for clinical treatment of patients with gene defects, and the application value is important. The OTC-circRNA-encapsulated lipid nanoparticles disclosed by the invention are good in stability in vivo, good in safety and long in curative effect lasting time.

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.

The invention relates to the modelling of a disorder called tubulinopathy, which refers to a wide range of cortical developmental malformations (CDM) resulting from defects in genes encoding tubulin proteins that regulate neuronal migration during brain development, by knocking out the tubulin gamma 1 (Tubg1) gene in zebrafish (Danio rerio) embryos using CRISPR / Cas9 technology. The transgenic animal in question allows the investigation of the phenotype and molecular pathological mechanisms of CDMs resulting from the deficiency of the Tubg1 protein during the developmental process. In the invention, the region located in the third exon of the Tubg1 gene in zebrafish is targeted and knocked out with a guide RNA having the nucleotide sequence SEQ ID NO: 1.

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 relates to a pharmaceutical combination comprising: a first conjugate comprising at least one effector molecule and a single-domain antibody (sdAb) for binding to a first cell-surface molecule; and comprising a saponin, a derivative thereof, or a second conjugate comprising a binding molecule for binding to a second cell-surface molecule and the saponin and / or the derivative thereof, wherein the saponin or the derivative thereof is a monodesmosidic or bidesmosidic triterpene glycoside. The invention also relates to a composition comprising the first conjugate and the saponin (derivative) or the second conjugate comprising the saponin (derivative). In addition, the invention relates to a pharmaceutical combination or composition of the invention, for use as a medicament, and for use in the treatment or the prophylaxis of a cancer, an auto-immune disease such as rheumatoid arthritis, an enzyme deficiency, a gene defect, a disease relating to a gene defect, an amyloidosis, a disease related to an enzyme deficiency, an infection such as a viral infection, hypercholesterolemia, primary hyperoxaluria, haemophilia A, haemophilia B, alpha-1 antitrypsin related liver disease, acute hepatic porphyria, transthyretin-mediated amyloidosis. Furthermore, the invention relates to an in vitro or ex vivo method for transferring the first conjugate of the invention from outside a cell to inside said cell, preferably to the cytosol of said cell.

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 provides the maintenance of programmed chronic liver injury in Fah gene-deficient animals and its application in the generation of xenogeneic liver models. The present invention provides a novel mechanism for the maintenance of programmed chronic liver injury in Fah gene-deficient animals and the generation of xenogeneic liver models. P ) method, which can enable long-term survival of animal models in a state of chronic liver injury and can achieve a high xenogeneic replacement rate after xenogeneic hepatocyte transplantation.

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.