85 results about "Coboglobin" patented technology

The disclosure features systems and methods for correcting a mutation in the human beta-globin (HBB) gene in a cell or population of cells. The disclosure also features methods of increasing repair of a DNA double stranded break (DSB) in an HBB gene by the homology-directed repair (HDR) pathway. The disclosure also features compositions for use in the methods.

The present subject matter relates to recombinant lentiviral transfer plasmids for producing lentiviral vectors with increased vector titer and performance. These transfer plasmids are constructed so that a central polypurine tract (cPPT) is centered between the lentiviral LTRs and include a 6x stop codon sequence block downstream of the 3' LTR. When the transfer plasmids comprise a globin expression cassette, the lentiviral vectors produced therefrom are useful for treating hemoglobinopathies by gene therapy. Transduced cells, pharmaceutical compositions and methods of treating or ameliorating hemoglobinopathies with these lentiviral vectors are also provided. Additional transfer plasmids, cells, and compositions are provided that are useful for delivering any gene of interest to a cell, as well as plasmids for production of lentiviral vectors for treating other erythroid-specific diseases or disorders such as anemia and cancer.

In certain embodiments, a lentiviral vector for the treatment of sickle cell disease (SCD) is provided. In certain embodiments, the vector comprises an expression cassette that encodes that an anti-sickling β-globin gene and an shRNA that inhibits expression of a BCL11A gene (BCL11A shRNA) wherein said expression cassette is in reverse orientation in the vector; a β-globin locus control region (LCR) comprising a reduced length hypersensitive site 1 (HS1) sequence, a reduced length hypersensitive site 2 (HS2) sequence, a reduced length hypersensitive site 3 (HS3) sequence, and a reduced length hypersensitive site 4 (HS4) sequence, where said anti-sickling β-globin gene is operably linked to the human β-globin locus control region.

The invention belongs to the technical field of biological peptide preparation, and particularly relates to a globin peptide stock solution feeding and mixing device for peptide copper preparation. Comprising a stirring tank, the top of the stirring tank is connected with a protective shell, and the bottom end of the stirring tank is connected with a discharge port; the stirring tank is connected with a quantitative feeding mechanism, and the protective shell is connected with a stirring and flapping mechanism; the quantitative feeding mechanism comprises a feeding box, a rotating disc and a discharging disc which are sequentially arranged from top to bottom. The stirring and beating mechanism comprises a motor, a second rotating shaft and a beater; bubbles on the surface of mixed liquid can be easily damaged through the stirring and flapping mechanism, the blockage problem is not prone to occurring when the quantitative feeding mechanism is installed, uniform feeding and mixing can be achieved through cooperation with stirring, and the requirement for quantitative feeding can be continuously met; the problems existing in the protein feeding process are solved.

The present invention concerns the use of a molecule chosen from a globin, a globin protomer or an extracellular hemoglobin of Annelids, for treating and / or preventing at least one complement-activation associated disease, preferably ischemia / reperfusion injury and / or transplant rejection.

This invention provides compounds for the treatment, prevention, or suppression of various pathological conditions (such as proliferative disorders like cancer, β-globin disorders, fibrosis, pain, neurodegenerative diseases, Prader-Willi syndrome, malaria, viral infections, myopathy, and autism) by inhibiting G9a. [Solution] The following general formula (I) TIFF2026062914000401.tif2449 A compound represented by or a pharmacoposly acceptable salt thereof is provided.

The present disclosure provides improved compositions for the homology directed repair of the human globin locus for the prevention, treatment, or amelioration of at least one symptom of a hemoglobinopathy.

This invention provides a high-recovery heme iron extraction method and apparatus using enzymatic hydrolysis-multi-stage centrifugal coupling, relating to the fields of biopharmaceuticals and fluid dynamics processing technology. The method first constructs a polyanionic electrolyte shielding system, utilizing electrostatic potential energy to induce conformational instability of globin and pre-exposure of hydrophobic cavities, reducing binding energy at the molecular level and solving the problem of heme's encapsulation resistance in high-concentration systems. Then, high-shear coupled enzymatic hydrolysis is performed within a micron-sized liquid film generated by a hypergravity field, utilizing the instantaneous synergy of mechanical shear stress and enzymatic degradation to achieve directional exfoliation of heme, eliminating secondary re-adhesion effects. Finally, directional phase transition regulation is performed based on density gradient drive, and a high-frequency pulsed pressure field is introduced for in-situ exchange washing, distinguishing and retaining impurities and crystal cores, outputting a high-purity, flavor-neutral heme iron product. This invention effectively improves the controllability of the extraction process and the stability of industrial continuous production.

The invention provides a characteristic protein spectrum model for detecting uremia and a construction method. Wherein the marker polypeptide composition is mainly carbamoyl hemoglobin of alpha / beta globin, and comprises eight marker polypeptides with the following mass-to-charge ratios: 7564 m / z, 7585 m / z, 7934 m / z, 7956 m / z, 8476 m / z, 15127 m / z, 15170 m / z, 15868 m / z, 15911 m / z and 16952 m / z. The mass spectrum model disclosed by the invention can be used for detecting uremia. The detection method provided by the invention is simple, easy to operate and high in accuracy, and provides a new method and idea for uremia detection.

The present invention relates to haptoglobin (Hp), and optionally hemopexin (Hx), for use in the treatment of traumatic brain injury (TBI) and in particular in the treatment or prevention of a secondary brain injury in a subject suffering from a TBI.

The invention provides corynebacterium glutamicum for synthesizing high-activity heme protein and application, and belongs to the technical field of genetic engineering. By enhancing globin gene transcription and optimizing heme prothetic group supply, the synthetic ability of hemoglobin and myoglobin is improved. The corynebacterium glutamicum constructed by the invention can enable the titers of soybean hemoglobin, clover hemoglobin, bovine myoglobin and porcine myoglobin to reach 1.10 g / L, 1.12 g / L, 0.56 g / L and 1.14 g / L respectively during shake flask fermentation, and enables the heme binding rates of produced S-Hb, C-Hb, B-Mb and P-Mb to be improved by 3.64 times, 2.38 times, 1.60 times and 1.49 times respectively, which can be similar to those of naturally extracted standard substances H-Mb and B-Hb.

The invention discloses an image processing method and device for judging suspension red blood cell hemolysis. The method comprises the following steps: acquiring a blood image set; the blood image set comprises a plurality of blood images and corresponding label information; acquiring a blood parameter information set; the blood parameter information set comprises a plurality of blood parameters and corresponding label information; the blood parameters comprise hemoglobin concentration, reticulocyte concentration, indirect bilirubin concentration, lactic dehydrogenase concentration and globin concentration; utilizing the blood image set and the blood parameter information set to construct a blood hemolysis composite detection model; based on the blood hemolysis composite detection model, processing the collected blood image and blood parameters to obtain hemolysis detection result information; the hemolysis detection result information is used for representing erythrocyte hemolysis information of the blood corresponding to the collected blood image and blood parameters.

Provided are materials and methods for treating patients with hemoglobinopathies, either ex vivo or in vivo. Also provided are materials and methods for deleting and / or mutating a portion of a human beta globin locus on chromosome 11 and one or more of: a BCL11 A gene on chromosome 2, and a DNA sequence that encodes a transcriptional control region of the BCL11 A gene on chromosome 2, in a human cell by genome editing and thereby increasing the production of fetal hemoglobin (HbF) in the genome-edited human cells.

A system and method for in-situ quantitative assessment of Bovine Mastitis (BM) in collected milk samples using optical imaging is disclosed. A bio-functionalized assay tray contains multiple wells, each having a gel with a specially prepared mixture of hemoglobin (Hb) and metal ions. At least one of the wells is filled with a reference milk sample which is characteristic of milk with no BM disease. Other wells are filled with collected milk samples. After waiting an interaction time, luminol and hydrogen peroxide solutions are added to the wells, causing chemiluminescent (CL) light emission. The intensity of CL light emitted by wells containing haptoglobin (Hp) is inhibited due to Hb-Hp binding. After waiting a CL light stabilization time, the tray is placed in a dark box, and a camera and image processor are used to analyze the CL light intensities. A calibration curve yields the Hp concentration in each well.

The present invention relates to an in vitro method for aiding the detection of hepatocellular carcinoma (HCC) in a subject comprising determining the amount of one or more glycan structures at position N207 of haptoglobin (i.e. Of the beta-chain of haptoglobin having the sequence given in SEQ ID NO: 1) in a sample obtained from the subject. The invention further discloses a glycan structure and a glycopeptide containing the glycan structure, and the glycan structure and the glycopeptide play an important role in HCC detection. Furthermore, the present invention relates to the use of one or more glycan structures at position N207 or a glycopeptide comprising haptoglobin N207 in combination with AFP and / or PIVKA in the detection of HCC.

The application discloses a monoclonal antibody of feline haptoglobin and application thereof, and the monoclonal antibody of feline haptoglobin or an antigen binding fragment thereof, and the monoclonal antibody of feline haptoglobin or the antigen binding fragment thereof comprises Hp-mAb8, Hp-mAb9 and / or Hp-mAb10, the amino acid sequences of CDR1, CDR2 and CDR3 of the heavy chain of the monoclonal antibody Hp-mAb8 are GFSLDGYD, IYVSDVT and ARDSDVGVSGYTFPDI respectively, and the amino acid sequences of CDR1, CDR2 and CDR3 of the light chain of the monoclonal antibody Hp-mAb8 are ESISTNR, PAS and QSGYATADVPNT respectively. The monoclonal antibody of feline haptoglobin has wider detection linearity, reduced cost, and can meet the budget of most cat-keeping families.

The invention belongs to the field of biological medicine. Specifically, the invention relates to an antibody specifically binding to Hb-CS protein, and an antigen binding fragment and application thereof. The antibody or the antigen binding fragment thereof provided by the invention can be specifically bound with Hb-CS protein instead of normal alpha globin, can be used for immunodetection of Hb-CS protein and effective recognition of Hb-CS protein positive red blood cells, and has important effect and value for development of alpha thalassemia drugs.

Methods of using one or more fumaric acid esters or pharmacologically active salts, derivatives, analogues, or prodrugs thereof to increase expression of fetal hemoglobin (HbF) are disclosed. The methods typically include administering to a subject an effective amount of one or more fumaric acid esters optionally in combination or alternation with hydroxyurea to induce HbF expression in the subject in an effective amount to reduce one or more symptoms of a sickle cell disorder, a hemoglobinopathy, or a beta-thalassemia, or to compensate for a genetic mutation is the human beta-globin gene (HBB) or an expression control sequence thereof. Pharmaceutical dosage units and dosage regimes for use in the disclosed methods are also provided.

A method for immunological detection of hemoglobin, the method comprising a step for performing immunological detection using an anti-hemoglobin antibody in the presence of hemoglobin and haptoglobin, the haptoglobin having the following characteristics (1): (1) at least a portion of an N-linked sugar chain is deleted. The present invention further provides a method for suppressing fluctuations in the detection value of hemoglobin, a method and a solution for stabilizing hemoglobin, a kit for detecting hemoglobin, and the haptoglobin and a method for producing the haptoglobin. According to the present invention, it is possible to detect hemoglobin by suppressing fluctuations in the detection value of hemoglobin due to haptoglobin.

The present invention relates to the technical field of genetic engineering. Disclosed are construction and use of a pichia pastoris chassis strain for synthesizing highly active heme proteins. In the present invention, a pichia pastoris chassis strain for efficiently synthesizing highly active heme proteins is constructed by enhancing the transcription of globin genes, inhibiting the degradation of globin, and optimizing the supply of heme prosthetic groups. At the shake flask level, the titers of porcine myoglobin, bovine myoglobin, soybean hemoglobin, clover hemoglobin, porcine hemoglobin α subunit, porcine hemoglobin β subunit, Vitreoscilla hemoglobin, and cytochrome P450-BM3 mutant (A82F / A328F) reach 5.02-286.53 mgL-1, and the heme binding rates of these heme proteins reach 13.24%-79.47%. The constructed heme-supplying pichia pastoris chassis strain and strategy in the present invention facilitate synthetization of other highly active heme proteins having a wide application range.

In alternative embodiments, provided are methods for detecting a cancer, the method comprising: obtaining a sample comprising biological fluids or cells from a subject or human; isolating extracellular vesicles (EVs) having a selected diameter range; determining the presence and concentration of one or at least two proteins, Haptoglobin (HP) and Catalase (CAT), in the selected diameter range from the sample; and correlating the presence of a combination of the one or at least two proteins with a source of the sample, wherein if HP and CAT are individually detected, or if HP and CAT are both detected, then cancer has been positively detected. Also provided are methods for treating, lessoning the symptoms of or decreasing the chance of recurrence of, a cancer comprising administering to an individual in need thereof an antibody (Ab) or an antigen (Ag) binding fragment that specifically binds haptoglobin (HP) and / or a haptoglobin-hemoglobin complex.

According to the present disclosure, a simple and accurate method for quantifying ergothioneine in a sample containing globin protein can be provided. A method for quantifying ergothioneine in a collected sample, comprising: (A) heating the sample; (B) mixing the heated sample with trichloroacetic acid; and (C) subjecting the sample obtained in step (B) to a quantitative operation; A method comprising:

Disclosed are methods for producing methemoglobin or polymerized methemoglobin. Also provided are pharmaceutical compositions comprising methemoglobin complexed with haptoglobin or polymerized methemoglobin, as well as methods of using thereof to treat cyanide and hydrogen sulfide poisoning.

The invention provides a marker polypeptide composition for detecting uremia and a mass spectrum model for evaluating the curative effect of uremia. Wherein the marker polypeptide composition is mainly carbamoyl hemoglobin of alpha / beta globin, and comprises eight marker polypeptides with the following mass-to-charge ratios: 7564 m / z, 7585 m / z, 7934 m / z, 7956 m / z, 8476 m / z, 15127 m / z, 15170 m / z, 15868 m / z, 15911 m / z and 16952 m / z. The marker polypeptide composition disclosed by the invention can be used for detecting uremia. The detection method provided by the invention is simple, easy to operate and high in accuracy, and provides a new method and idea for uremia detection.

The present invention relates to haptoglobin or a nucleic acid encoding haptoglobin for use in the treatment or prevention of excessive erectile response and / or prevention of permanent erectile dysfunction. Furthermore, the present invention relates to a pharmaceutical composition for use in the treatment or prevention of excessive erectile response and / or prevention of permanent erectile dysfunction wherein the pharmaceutical composition comprises an adeno-associated virus (AAV) vector bearing a transgene encoding a haptoglobin gene. The excessive erectile response may be priapism, such as priapism associated with sickle cell disease (SCD).

Here, the inventors developed a strategy to modify the chromatin status of HSPCs at the HBG promoters to reactivate HbF expression. In particular, the inventors used from 1 to 4 single guide RNA (sgRNA) molecules spanning from the -220 to the -20 region of the HBG promoters together with CRISPR-based epigenome editors, namely dCas9-CBPcore and Tet1-dCas9. The first editor is capable of inserting histone acetylation while the second editor is performing DNA demethylation. Both epigenetic marks are associated with active transcription and are present in fetal erythroid cells expressing HbF. This strategy allows the ex vivo modification of adult HSCs to recreate a fetal-like epigenetic context leading to HbF production. Moreover, it avoids the genotoxicity associated with classical genome editing tools relying on DNA cleavage. Thus, the present invention relates to a method of increasing the expression of gamma globin in a population of eukaryotic cells through epigenome editing.

In certain embodiments a lentiviral vector for the treatment of sickle cell disease (SCD) is provided. In certain embodiments the vector comprises an expression cassette that encodes that an anti-sickling β-globin gene and an shRNA that inhibits expression of a BCL11A gene (BCL11A shRNA) wherein said expression cassette is in reverse orientation in the vector; a β-globin locus control region (LCR) comprising a reduced length hypersensitive site 1 (HS1) sequence, a reduced length hypersensitive site 2 (HS2) sequence, a reduced length hypersensitive site 3 (HS3) sequence, and a reduced length hypersensitive site 4 (HS4) sequence, where said anti-sickling β-globin gene is operably linked to the human β-globin locus control region;.

Provided is a method of treating or alleviating one or more pathologies associated with β- thalassemia in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of an anti-matriptase-2 antibody or antigen-binding fragment thereof. The one or more pathologies may be insoluble liver iron stores: α-globin precipitates in ery throid cells; reactive oxidized species formation; apoptosis of erythroid cells; reticulocytosis; or a combination thereof.

BCL11A plays a critical role in the regulation of hemoglobin production, specifically in the switch from fetal hemoglobin (HbF) to adult hemoglobin (HbA) during development. BCL11A represents a target to develop therapies for β-hemoglobinopathies by reactivating HbF. The inventors leading to a better yield for the proteomic analysis of histidine phosphorylations in a whole proteome. They identify a phosphorylation on histidine of BCL11A by immunoprecipitation of BCL11A and by the detection of its phosphorylations on histidines by Western blot. Furthermore, the knock down of NME1 and NME2 by CRISPR / Cas9 in HUDEP2 erythroid cell line induces the expression of fetal hemoglobin, suggesting that NME1 / 2 could be involved in fetal to adult globin switch probably through the regulation of histidine phosphorylation of BCL11A. HUDEP-2 cell line is still able to differentiate until the orthochromaic erythroblast stage and do not show any increase in cell death.

An immunological measurement method for hemoglobin, comprising a step of performing the immunological measurement using an anti-hemoglobin antibody under coexistence of the hemoglobin and haptoglobin, the haptoglobin having a characteristic (1) below: (1) at least a portion of an N-linked glycan is deleted. The present invention further provides a method for suppressing change in measurement values of hemoglobin, a method and a solution for stabilizing hemoglobin, a hemoglobin measurement kit, and the haptoglobin and a method for producing the same. According to the present invention, hemoglobin can be measured while suppressing haptoglobin-associated change in hemoglobin measurement values.