63 results about "Gene defect" patented technology

The invention discloses an application of an HERP gene knockout mouse model in obesity and metabolic disorder diseases. The invention finds that compared with a wild type high-fat group, HERP gene knockout can cause phenotypes such as early obesity, more serious obesity degree, increase of fat weight ratio, aggravation of adipose tissue inflammation, dyslipidemia and glucose metabolism disorder of mice during high-fat feeding. And the HERP gene is knocked out, so that the adipocyte differentiation is increased. The HERP gene knockout mouse is more sensitive to nutrition, obesity can occur more quickly during high-fat feeding, symptoms such as fat amplification, fat inflammation and glucose and lipid metabolism disorder are more serious, and the HERP gene knockout mouse can be used for molecular mechanism research and drug screening of obesity, fat tissue and glucose and lipid metabolism disorder. It is further found that cilostazol can significantly relieve mouse obesity and lipid metabolism disorder caused by HERP gene defects, but has no obvious weight losing effect on normal genotype mice, and a new strategy is provided for precise treatment.

The invention relates to the technical field of digital cell models, in particular to a construction method and system of a digital cell model and a storage medium. The method comprises the following steps: acquiring target cell data, extracting a target cell structure, and performing molecular physiological function analysis in combination with the cell structure and the data to obtain molecular physiological function data of cells; performing cell molecule metabolism network analysis to obtain cell molecule metabolism network data, and constructing a digital cell model; through the model, the reaction of the cells under the environmental pressure can be simulated, the attenuation of the physiological state of the cells can be estimated, and then the gene defects of the cells can be analyzed; according to the cell gene defect, adjusting the target cell data to obtain cell gene adjustment data; according to the method, the cell model is constructed, so that the dynamic change analysis of the cells is more accurate.

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 disclosure relates to the use of IgE for identifying individuals with genetic defects that lead to the expression of protein truncations, extended proteins, to a loss of protein expression or to the expression of mutated proteins. The method is based on a skin prick test, wherein IgE that is specific for the protein of interest is administered onto the skin. If the protein or protein variant that is specifically identified by IgE is present in the skin, the IgE, which was allowed to enter the skin by the skin prick, binds the target protein and then the protein-bound IgE triggers mast cells and / or basophiles in the skin to release granules, resulting in the development of a transient allergic reaction.

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 discloses a special culture medium for inducing hematopoietic stem cells to differentiate into T lymphocytes in vitro aiming at Foxn1 gene defects, a kit and application of the special culture medium and the kit, and relates to the technical field of cell culture. The simplified and efficient culture medium combination and culture process are included, the complex reagent preparation process is optimized into two independently packaged kits, the operation difficulty, pollution risk and cost input of organoid culture are remarkably reduced, additional matrix materials do not need to be added, and the stability of the cell growth state is facilitated. The culture medium is applied to hematopoietic stem cell culture and differentiation of T lymphocytes. The method is expected to be suitable for hematopoietic stem cells from marrow sources of other mammals including human beings, and the culture system is easy in source obtaining, low in cost, simple in operation process, short in induction time and beneficial to large-scale and industrialization.

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; anda 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 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 invention discloses construction and application of a TAGLN2 gene defect type mouse model, which utilizes a CRISPR / Cas9 gene editing technology, uses gRNA to guide Cas9 protein to respectively shear at specific sites at the upstream of a second exon and the downstream of a fifth exon of a TAGLN2 gene, and realizes TAGLN2 gene knockout. The mouse model constructed by the invention provides a basis for researching the molecular mechanism of the TAGLN2 gene, and is beneficial to researching the pathogenesis of metabolic diseases.

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.

The invention discloses application of a traditional Chinese medicine composition for resisting wild and gene defect types of stenotrophomonas maltophilia, and relates to the field of microbiology, and the traditional Chinese medicine composition comprises 10-20 mg of plica hydrochloride, 5-10 mg of gallic acid, 8-15 mg of allicin, 6-12 mg of chlorogenic acid and 7-14 mg of forsythin. Compared with the prior art, the composition has the advantages that all the components are matched with one another to play a synergistic effect, growth and reproduction of stenotrophomonas maltophilia can be more efficiently and comprehensively inhibited, the antibacterial effect of the medicine is enhanced, the standardization degree of the experiment and production process is improved, the quality and stability of the medicine are guaranteed, and the composition is suitable for popularization and application. And large-scale production, popularization and application are facilitated.

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 present invention provides an application of an ER beta agonist in the preparation of a drug for treating Duchenne muscular dystrophy, belonging to the field of pharmaceutical technology. Experiments of the present invention show that after treatment with the ER beta agonist diarylpropionitrile (DPN), the damaged area of muscle decreases and the inflammatory infiltration reduces; meanwhile, DPN can enhance the skeletal muscle strength function of B10-DMD-KO mice, alleviate the muscle tissue damage caused by the self-gene defect of B10-DMD-KO mice, promote the formation of new muscle fibers and accelerate their maturation, ultimately promote the regeneration of skeletal muscle fibers and the recovery of skeletal muscle strength, and can be used to improve the muscle regeneration disorder caused by Duchenne muscular dystrophy, providing a theoretical basis for the development of drugs for treating Duchenne muscular dystrophy. In addition, compared with the existing technical means, DPN has the advantages of lower treatment cost and less side effects, and thus has good application prospects in the preparation of drugs for treating Duchenne muscular dystrophy.