26 results about "Coboglobin" patented technology

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 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.

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.

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.

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.

The invention discloses an anti-zeta globin antibody and application thereof, and relates to the field of antibodies. The anti-zeta globin antibody disclosed by the invention comprises a heavy chain complementarity determining region and a light chain complementarity determining region, provides an important raw material source for zeta globin detection, and has good activity and specificity.

326 Abstract of the Disclosure The present invention features compositions and methods for editing deleterious mutations associated with hemoglobinopathies, such as sickle cell disease (SCD). In particular embodiments, the invention provides methods for correcting mutations in a beta globin 5 polynucleotide using modified adenosine base editors termed “ABE8” having unprecedented levels (e.g., >60-70%) of efficiency. 326 20 26 20 47 29 18 J un 2 02 6 1 8 J u n 2 0 2 6 2 0 2 6 2 0 4 7 2 9 3 2 6

The present invention features compositions and methods for editing deleterious mutations associated with hemoglobinopathies, such as sickle cell disease (SCD). In particular embodiments, the invention provides methods for correcting mutations in a beta globin polynucleotide using modified adenosine base editors termed “ABE8” having unprecedented levels (e.g., >60-70%) of efficiency.

The present invention relates to a polynucleotide construct comprising a hemoglobin subunit alpha-hemoglobin subunit beta (HBA-HBB) hybrid gene construct for enhancing the potency of gene therapy for the β-hemoglobinopathies, particularly β-thalassemia and sickle cell disease (SCD). The polynucleotide construct comprising elements that are operatively connected to each other in the following sequence: HBB locus control region (HBB-LCR), HBA promoter, and β-like globin gene. Additionally, the HBA-HBB gene construct further comprises a microRNA-based short hairpin RNA (shRNAmir) targeting one of the endogenous HBA or HBB genes to increase the ratio of vector-encoded HBBT87Q to endogenous HBA and β-like globin chains while maintaining high vector titers.

Enhancing fetal hemoglobin (HbF) production through targeted promoter editing using base editing technologies. An embodiment includes a composition for enhancing fetal hemoglobin (HbF) expression in mammalian cells, the composition comprising a base editing system comprising at least two guide RNAs comprising targeting sequences selected from SEQ ID NO: 1 to SEQ ID NO: 5. Specifically, it involves the design and use of single guide RNAs (sgRNAs) targeting key regulatory elements within the gamma-globin (HBG1 / 2) promoter. The method combines the use of adenosine base editors to introduce mutations, creating new binding sites for transcriptional activators like TAL1 and KLF1, and disrupting repressor binding sites such as BCL11A and ZBTB7A / LRF. This dual-targeting approach significantly increases HbF expression, offering a potential therapeutic strategy for treating beta-hemoglobinopathies like sickle cell disease and beta-thalassemia.

The present invention features compositions and methods for editing deleterious mutations associated with hemoglobinopathies, such as sickle cell disease (SCD). In particular embodiments, the invention provides methods for correcting mutations in a beta globin polynucleotide using modified adenosine base editors termed “ABE8” having unprecedented levels (e.g., >60-70%) of efficiency.

The invention provides anti-βS globin antibodies or antigen binding fragments thereof.

The present application relates to synthetic MAR fragments, expression vectors, expression systems and their applications, and belongs to the field of biotechnology. The novel synthetic MAR fragments are MAR-1, MAR-2 and MAR-3. The MAR fragments of the present application are designed and synthesized based on the common sequence characteristics of beta-globin MAR sequence, X-29 sequence, beta-interferon MAR sequence and MAR 1-68 sequence. It is found that when MAR-1, MAR-2 and MAR-3 are used simultaneously for the expression of exogenous proteins in CHO cells, the effect of MAR-1 is the best. The expression amount of exogenous proteins can be increased by 5.04-5.47 times compared with the system without MAR fragments. More preferably, the 8-copy tandem repeat sub-DNA fragment composed of MAR-1 fragment has better ability to increase the expression amount.

The application discloses an image processing method and device for judging hemolysis of suspended red blood cells, and 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, lactate dehydrogenase concentration and globin concentration; a blood hemolysis composite detection model is constructed by using the blood image set and the blood parameter information set; the collected blood image and blood parameter are processed based on the blood hemolysis composite detection model, and hemolysis detection result information is obtained; the hemolysis detection result information is used for representing the red blood cell hemolysis information of the corresponding blood of the collected blood image and blood parameter.

The present invention relates to the use of a molecule selected from among the oxygen transporters of marine invertebrate animals, preferably from among a globin, a globin protomer or an extracellular hemoglobin of annelids, as a bactericide, in particular for preventing and / or treating periodontal disease.

The clinical history of β-hemoglobinopathies shows that the severity is mitigated by the reduction of α-globin expression, resulting from co-inheritance of α-thalassemia. The inventors identified several mutations (T>C or A>G) that can disrupt binding motifs of transcription factors using CBE- and ABE-mediated base-editing approaches. In particular, the inventors designed gRNAs that, when combined with CBEs or ABEs, disrupt binding sites for transcriptional activators (GATA1 and NF-E2) in the MCS-R2 and recapitulate the beneficial α-globin reduction observed in patients presenting both β-hemoglobinopathies and α-thalassemia. Accordingly, the present invention relates to base editing approaches for the treatment of β-hemoglobinopathies.

1. An RNA molecule comprising in the 5'3' direction, a 5'-terminal transcription start site, a 5' untranslated region (5'UTR), a Kozak sequence, an open reading frame (ORF) comprising a coding region, and a 3' untranslated region (3'UTR), wherein a) the 5'UTR comprises a transcript of the 5'UTR of the human alpha-globin nucleic acid sequence SEQ ID NO:1, a fragment or variant thereof which is at least 90% identical to SEQ ID NO:1; and b) the 3'UTR comprises a transcript of: i) the human Glucose 6-phosphate isomerase 1 (GPI1) nucleic acid sequence SEQ ID NO:19, or a fragment of SEQ ID NO:19 comprising at least 50% of the full-length sequence, or a variant of SEQ ID NO:19 which is at least 90% identical to SEQ ID NO:19; or ii) the human nascent polypeptide associated complex subunit alpha (NACA) nucleic acid sequence SEQ ID NO:21, or a fragment of SEQ ID NO:21 comprising at least 50% of the full-length sequence, or a variant of SEQ ID NO:21 which is at least 90% identical to SEQ ID NO:21; or iii) the human magnesium transporter (MRS2) nucleic acid sequence SEQ ID NO:23, or a fragment of SEQ ID NO:23 comprising at least 50% of the full-length sequence, or a variant of SEQ ID NO:23 which is at least 90% identical to SEQ ID NO:23; or iv) a combination of any two or more of i), ii), or iii).

Provided herein are compositions for increasing Apolipoprotein L1 (ApoL1) in target cells. The ApoL1 can be a recombinant protein or an endogenous protein optionally in a ApoL1-containing complex. Antibodies and other binding molecules that specifically bind, Apolipoprotein L1 (ApoL1) and Haptoglobin related protein (Hpr). In preferred embodiments, the antibodies and other molecules bind to an ApoL1-containing complex such as a Trypanosome Lytic Factor (TLF), preferably under physiological conditions. In preferred embodiments, the antibodies and antigen binding fragments are bispecific, trispecific, and multispecific molecules that can bind to the ApoL1-containing complex and further bind to a cell specific antigen. Methods of using such molecules to increase flux of ApoL1-containing complexes into target cells expressing the cell specific antigen are also provided. Such increase in ApoL-containing complexes can increase cell death. In preferred embodiments, the target cells are cancer cells such as blood cancer cells or solid tumor cells.

Provided herein are compositions and methods for the treatment of hemolysis in pulmonary tissue. Also provided herein are methods of purifying proteins including apo-transferrin, haptoglobin, hemopexin, and combinations thereof.