58 results about "Thalassemia" patented technology

The present disclosure relates to compositions and methods of increasing levels of fetal hemoglobin (HbF) in cells. The present disclosure further relates to methods for treating patients suffering from blood cell diseases, including those associated with reduced amounts of functional adult hemoglobin (HbA), such as sickle cell disease and β-thalassemias

The invention relates to the technical field of stem cells, in particular to a lentivirus envelope plasmid combination and application thereof, a lentivirus and a packaging method thereof and a method for transduction of hematopoietic stem cells. The invention provides an envelope plasmid combination for lentivirus packaging, which is composed of lentivirus packaging plasmids containing VSVG glycoprotein and lentivirus packaging plasmids containing BaEV glycoprotein in a ratio of 3: 7. The invention further provides a method for transduction of the hematopoietic stem cells by the lentivirus, the method is simple and convenient to operate, the long-term dryness of the hematopoietic stem cells in vitro can be maintained, efficient and stable transduction of the hematopoietic stem cells can be realized, and the transduction rate is greater than 90%. The lentivirus transduction method hematopoietic stem cells can be used for hematopoietic stem cell gene therapy hematopoietic system genetic diseases, such as severe combined immunodeficiency, beta-thalassemia and sickle cell disease, Wiskott-Aldrich syndrome and the like, and the application prospect is good.

The invention relates to a method and device for simultaneously detecting multiple gene mutations related to thalassemia, and the method comprises the following steps: obtaining nanopore sequencing data of a to-be-detected sample, the to-be-detected sample comprising amplification products of multiple PCR primer pairs for simultaneously detecting multiple gene mutations related to thalassemia; performing quality control screening on the nanopore sequencing data according to the amplification length of the multiple PCR primer pair to obtain first target sequencing data; according to the first target sequencing data, obtaining the sequence number of the amplification product of the PCR multiple primer pair, and according to the sequence number of the amplification product of the PCR multiple primer pair, determining the gene mutation information related to thalassemia of the to-be-detected sample. According to the application, deletion mutation and non-deletion mutation related to thalassemia can be detected at the same time, and the accuracy of HBA1 and HBA2 gene detection results is improved.

Aspects of the present disclosure provide anti-TMPRSS6 antibodies and methods of using the same to promote hepcidin expression and treat iron overload related disorders such as hemopigmentation, sickle cell disease, thalassemia, hemolysis, Diamond-Blackfan anemia, myelodysplastic syndrome (MDS), and blood transfusion.

The invention relates to the field of medical diagnosis, in particular to a thalassemia red blood cell morphology rapid analyzer based on a micro-fluidic chip, which comprises a micro-fluidic chip module, a shooting module, an image recognition module, a temperature control module and a display module, the temperature control module is used for controlling the temperature of the micro-fluidic chip module, and the shooting module is used for shooting the movement and deformation process of red blood cells in the micro-fluidic chip module. The image recognition module is used for carrying out image recognition on the shot image and analyzing the performance of the red blood cells from dynamic and static directions according to an image recognition result; and the display module is used for displaying a recognition result and an analysis result of the image recognition module. According to the scheme, the deformation capacity and the recovery capacity of the red blood cells are judged from the static direction and the dynamic direction, and the recognition accuracy of diseases such as thalassemia is improved.

A compound containing a bis(azanylylidene) sulfonyl structure of formula (I) as a PKR agonist and / or USP9X inhibitor, which can be used for treating related diseases mediated and regulated by PKR and USP9X, wherein the related diseases comprise, but are not limited to: sickle-cell anemia, β-thalassemia, hereditary non-spherocytic hemolytic anemia, hemolytic anemia, hereditary spherocytosis, hereditary elliptocytosis, abetalipoproteinemia, paroxysmal nocturnal hemoglobinuria, acquired hemolytic anemia, congenital anemia, anemia of chronic diseases, colorectal cancer, kidney cancer, pancreatic cancer, breast cancer, lung cancer, esophageal cancer, melanoma, lymphoma, glioblastoma, or multiple myeloma.

The present invention relates to products and compositions and their uses. In particular, the invention relates to nucleic acid products that interfere with the expression of the TMPRSS6 gene or inhibit its expression and to therapeutic uses such as for the treatment of hemochromatosis, porphyria and hematological disorders such as β-thalassemia, sickle cell disease and iron overload from transfusions or myelodysplastic syndrome.

Methods and compositions for increasing hemoglobin levels (e.g., fetal hemoglobin) and / or gamma-globin in a cell or subject by the administration of at least one FTP A inhibitor and / or at least one TIPRL inhibitor to the cell or subject is disclosed. In another aspect methods of treating and / or preventing a hemoglobinopathy (e.g., sickle cell disease) or thalassemia in a subject by the administration at least one PTPA inhibitor and / or at least one TIPRL inhibitor to the subject in need thereof are further disclosed.

The invention provides a primer group, a method and a kit for detecting thalassemia, which can be used for simultaneously detecting thalassemia related genes, related regulatory regions and modified gene mutations. According to the method, multiple regions and multiple mutations of HBA1, HBA2, HBB and other genes, related regulatory regions (LCR, 3 'HS, HS-40 and MCS-R) and modified genes (HBD, MYB, BCL11A and KLF1) are detected at the same time based on multiple PCR amplification and three-generation sequencing, amplification of related gene deletion type and non-deletion type mutations can be achieved at the same time in a single reaction tube through multiple PCR; a third-generation sequencing platform (an ONT sequencing platform and a PacBio company sequencing platform) is subsequently adopted for subsequent detection, the method is easy and convenient to operate, multiple PCR and a third-generation sequencing library are reliable in quality and high in repeatability, application of the third-generation sequencing technology to clinical detection is facilitated, and the method is suitable for clinical detection. According to the invention, various deletion and non-deletion mutation, complex structure variation and the like can be detected at the same time; when two or more mutations exist on the HBA1 / 2 or HBB gene locus at the same time, cis-mutation or trans-mutation can be distinguished.

The present application provides materials and methods for treating hemoglobinopathies. More specifically, the application provides methods for producing progenitor cells that are genetically modified via genome editing to increase the production of fetal hemoglobin (HbF), as well as modified progenitor cells (including, for example, CD34+ human hematopoietic stem cells) producing increased levels of HbF, and methods of using such cells for treating hemoglobinopathies such as sickle cell anemia and β-thalassemia.

The present invention provides the use of thyroid hormone and its analogs in the preparation of a drug for treating α-thalassemia. Specifically, the drug can be used to regulate ζ-globin gene expression. During K562 cell differentiation, the thyroid hormone analogs can specifically and significantly upregulate the expression of the ζ-globin gene (HBZ) by as much as 50 times. After treatment with thyroid hormone and its analogs in model animal zebrafish embryos, the expression of the ζ-globin gene (hbae5) can also be specifically upregulated by as much as 30-70 times. Therefore, the present invention uses thyroid hormone and its analogs to specifically activate the expression of the ζ-globin gene, that is, to reactivate the silenced ζ-globin gene in α-thalassemia patients to inhibit the destruction of red blood cells. This method provides a method for preparing a drug for treating α-thalassemia, provides an economical, safe and effective method for the treatment of α-thalassemia, and can be widely promoted and used.

The present invention discloses a kit and a detection method for detecting gene mutation sites based on fluorescent quantitative PCR using a lock ring probe. The present invention combines the lock ring probe ligation technology in RCA technology with real-time fluorescent quantitative PCR technology, utilizes the lock ring probe ligation characteristics to detect point mutations, and utilizes qPCR technology to achieve signal amplification with high sensitivity and good specificity. It has been used to detect the T478K mutation site of the SARS-cov2-Delta mutant strain, the CD17 mutation site of thalassemia, and the 531 mutation site of the rpoB gene of the rifampicin-resistant strain of Mycobacterium tuberculosis; wherein the minimum detection limit of SARS-cov2 can reach 54.9fM, and the detection limits of thalassemia and tuberculosis resistance are 95.35zM and 55.12aM, respectively. This method can also be widely used in the detection of gene mutation sites related to other diseases.

IVS1-110 (G>A) is one of the most common β-thalassemic mutations in the Middle East and Mediterranean area, representing >75% and >40% of β-thalassemic mutations in Cyprus and Greece, respectively. This point mutation is classified as a severe β+ mutation, and homozygous patients or compound heterozygotes harboring this mutation in combination with a β0 mutation have a clinical phenotype similar to β0 / β0 patients. Here, the inventors exploited adenine base-editors (ABEs) to correct the IVS1-110 (G>A) mutation in HSPCs from β-thalassemia patients and demonstrated the potential of this strategy to correct the pathological phenotype C observed during erythroid differentiation. In particular the inventors demonstrated that reverting the IVS1-110 (G>A) mutation using base editing corrected the β-thalassemic cell phenotype in vitro and in vivo. The present invention thus relates to base editing approaches for the treatment of β-thalassemia including sickle β-thalassemia.

The present application relates to the use of idasanutlin, or a pharmaceutically acceptable salt, a solvate, an isomer, or a functional derivative thereof for the treatment of hemoglobinopathies, including sickle cell disease, thalassemia, sickle cell beta thalassemia (Hb S / β Th), and leukocytosis as well as myeloproliferative conditions, polycythemia, and acute and chronic hemolytic anemia. It was found that idasanutlin increases HbF levels in multipotent erythroleukemia, hematopoietic stem cells, and sickle cell disease cells to provide another therapy for treatment of sickle cell disease.

The present invention provides the use of ATR / Chk1 signaling pathway inhibitors in promoting enucleation of red blood cells, and experiments prove that ATR / Chk1 signaling pathway inhibitors can promote enucleation in the in vitro differentiation system of erythroid cells derived from fetal liver and the in vitro differentiation system of erythroid cells derived from peripheral blood, and can promote enucleation of erythroblasts in bone marrow. ATR / Chk1 signaling pathway inhibitors can also promote enucleation of erythroblasts in the bone marrow and spleen of thalassemia subjects, and have good application prospects in the treatment of diseases related to abnormal enucleation of red blood cells.

The present application relates to use of a hypoxia-inducible factor-prolyl hydroxylase inhibitor (HIF-PHI) in rare anemia. Specifically disclosed in the present application is use of certain hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) in the treatment of anemia of myelodysplastic syndromes (MDS anemia), beta-thalassemia (β-thalassemia), and / or sickle cell disease (sickle cell anemia, SCD anemia).

Embodiments herein provide specially designed synthetic BCL11A-targeting microRNAs for RNA polymerase II expression, and methods of use to treat hemoglobinopathies, such as sickle cell disease or thalassemia, by increasing the expression levels of fetal hemoglobin levels.

An object of the present invention is to provide an eluent for suppressing bimodality of hemoglobin F which is a β - thalassemia disease marker in hemoglobin analysis in cation exchange chromatography and stably separating hemoglobin F without depending on the type of diluent, and a method for separating hemoglobin F and a method for diagnosing hemoglobin F using the eluent.SOLUTION: In the analysis of a hemoglobin sample using cation exchange chromatography, the problem is solved by an eluent having a pH of 5.0 to 6.0, which is passed when separating and quantifying hemoglobin F from the hemoglobin sample, wherein the eluent contains at least one or more pH buffers, and a relationship between the pH of the eluent and a pKa value in a range of 5.0 to 7.0 among pKa values indicated by the pH buffers is a relationship of pH ≤ pKa ≤ pH + 1.0.SELECTED DRAWING: Figure 1

The invention relates to the crossing field of medical image processing and artificial intelligence technology, in particular to a bone marrow cell morphology artificial intelligence analysis method and system, and the method comprises the steps: obtaining a multi-view high-resolution image of a bone marrow smear and / or a peripheral blood smear under the oil immersion magnification, and carrying out the preprocessing; carrying out red blood cell coarse segmentation and fine classification through a cascade deep network, and identifying target-shaped, broken, teardrop-shaped and elliptical red blood cells; correcting broken red blood cell counting by adopting a fragment aggregation correction algorithm; and calculating an MCI value in combination with blood routine test data, and carrying out weighted fusion on the MCI value and the abnormal red blood cell proportion to generate a thalassemia screening comprehensive score. Therefore, the problems of low manual identification efficiency, insufficient abnormal red blood cell identification accuracy, large broken red blood cell counting deviation, difficulty in distinguishing multiple types of abnormal red blood cells, lack of organic combination with clinical diagnosis indexes and the like are solved, and the efficiency and accuracy of morphological analysis of bone marrow cells are improved; and a reliable basis is provided for diagnosis of diseases such as thalassemia.

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to application of a qi-tonifying and blood-maintaining preparation in preparation of a medicine for treating thalassemia. Researches show that the preparation for tonifying qi and maintaining blood is used for treating thalassemia and can effectively improve the anemia state and iron metabolism disorder of patients. Specifically, the medicine can significantly improve the hemoglobin level, increase the red blood cell count and the red blood cell average volume, and improve the serum iron content, the ferritin content and the reticulocyte proportion. The results show that the qi-tonifying and blood-maintaining preparation has the effect of promoting the bone marrow hematopoiesis function and can regulate and optimize the iron metabolism process. The invention provides an economical, effective and convenient treatment scheme for the thalassemia patient.

The present invention relates to new compounds of general formula (I), and Het-2 is an optionally substituted bicyclic heteroaryl of the following formula, pharmaceutical compositions comprising the same, and their use as medicaments, in particular as inhibitors of ferroportin, more particularly for the prevention and / or treatment of diseases or iron metabolism disorders caused by the lack of hepcidin, such as in particular iron overload conditions, such as in particular thalassemia and hemochromatosis.

The invention belongs to the technical field of biological medicines, and particularly relates to a pharmaceutical composition for treating thalassemia and application thereof. The invention provides a pharmaceutical composition for treating thalassemia, which comprises: (a) a cell population containing a first type of cells and a second type of cells, the cell population can be used for differentiating to generate red blood cells, target loci of the first type of cells are edited to increase red blood cells expressing functional hemoglobin generated by differentiation of the cell population, and target loci of the second type of cells are edited to generate target loci of the second type of cells; the target gene loci of the second type of cells are not edited; (b) a mobilizing agent. The medicine composition can achieve the effect of treating thalassemia through cell transplantation without removing marrow, and the clinical treatment risk of a patient is reduced.

The present invention discloses the use of methyl α-D-glucopyranoside in the preparation of thalassemia therapeutic drugs. Comprehensive analysis shows that when methyl α-D-glucopyranoside was intraperitoneally injected into β-thalassemia mice, it was found that methyl α-D-glucopyranoside was one of the metabolites with the largest down-regulation amplitude, and had multiple beneficial effects on Th3 / + mice, including increasing the total red blood cell count, hemoglobin level and hematocrit, and reducing the coefficient of variation of the red blood cell volume distribution width; reducing the iron content in the liver, splenomegaly and iron content in the spleen; increasing the GSH / GSSG ratio, reducing the ROS level, reducing the apoptosis rate of peripheral blood cells, and increasing the lifespan of red blood cells. After GP treatment, the ineffective hematopoiesis, anemia and iron overload of thalassemia mice were effectively alleviated without obvious toxic side effects. The treatment is convenient to implement, and GP is cheap and easy to store.

The invention discloses a method and a composition for activating zeta-globin gene expression. The method comprises the step of artificially forming an enhancer element containing an NTG-N (7-8)-WGATAR sequence or an NAA-N (7-8)-WGATAR sequence in a DNA (deoxyribonucleic acid) sense strand or an antisense strand in a promoter region of a zeta-globin gene through homologous recombination repair by using a CRISPR-Cas9 system. The invention also discloses gRNA, ssODN, a composition and a cell, and application of the gRNA, the ssODN, the composition and the cell in preparation of a medicine for treating alpha-thalassemia. According to the method, overexpression of exogenous globin genes is not needed, and the safety risk of gene therapy is reduced. Moreover, expression of the zeta-globin gene is activated, so that the method can be suitable for various types of alpha-thalassemia patients and alpha-gene deletion or mutation patients, and is not limited to alpha-thalassemia caused by a certain mutation site.

The present application relates to the technical field of stem cells, in particular to a lentivirus envelope plasmid combination and application thereof, a lentivirus and a packaging method and a method for transducing hematopoietic stem cells. The present application provides an envelope plasmid combination for lentivirus packaging, which is composed of lentivirus packaging plasmids containing VSVG glycoprotein and lentivirus packaging plasmids containing BaEV glycoprotein in a ratio of 3:7; further provided is a method for transducing hematopoietic stem cells with lentivirus, which is simple to operate, can maintain the long-term stemness of hematopoietic stem cells in vitro, can realize efficient and stable transduction of hematopoietic stem cells, and the transduction rate is greater than 90%. The hematopoietic stem cells transduced by the lentivirus transduction method of the present application can be used for hematopoietic stem cell gene therapy of hematopoietic system genetic diseases, such as severe combined immunodeficiency, beta-thalassemia and sickle cell disease, Wiskott-Aldrich syndrome, and has a good application prospect.

The invention provides novel application of gypenoside A. Verification shows that the gypenoside A can improve problems caused by cell iron ion accumulation by improving the level of cell iron metabolism related protein, and can be used for preparing medicines for treating diseases caused by iron metabolism disorder, such as neurodegenerative diseases, thalassemia and hemochromia.

The invention discloses a thalassemia treatment method based on a stem cell technology and application. The thalassemia treatment method comprises the following steps: collecting a peripheral blood sample of a patient, and carrying out stem cell isolated culture; constructing a nucleic acid aptamer by combining a vascular cell adhesion molecule-1 and a stromal cell-derived factor-1 in a bone marrow microenvironment; connecting a nucleic acid aptamer, a cell adhesion promoting peptide and a stem cell growth factor, and constructing a homing guiding reagent; preparing nano liposome and nano polymer particles; the nucleic acid aptamer is connected to the surfaces of the nano-liposome and the nano-polymer particles, and is grafted with a temperature-responsive material to obtain the nano-carrier with a responsive release function; stem cell growth factors and platelet-derived growth factors are mixed with gelatin microspheres to form a slow release system; the cultured stem cells are mixed with a homing guide reagent, a nano-carrier and a slow release system, and are transplanted into the body of a patient through intramedullary injection. The stem cell homing efficiency can be improved, and the treatment effect on thalassemia is improved.

The invention provides a primer probe composition for detecting Southeast Asia deletion type alpha-thalassemia and application of the primer probe composition, and belongs to the technical field of disease screening. The primer probe composition can be used for detecting samples with the mutation rate as low as 2% and the mutation gene concentration as low as 101 copies / mu L, and is suitable for trace sample analysis. According to the present invention, the Southeast Asia type alpha-thalassemia with the highest carrying rate is adopted as the breakthrough, the total DNA of the non-enriched cervical exfoliated cell sample can be directly extracted, the ddPCR is adopted to perform absolute quantification on the content of the mutant type alpha gene cluster and the wild type alpha gene cluster in the sample, and the ratio is calculated; the purpose of identifying the genotype of fetal thalassemia through an enrichment-free cervical exfoliated cell specimen is achieved by utilizing the proportion. According to the method, indirect inference of the fetal genotype is realized by dynamically analyzing the wild type / deletion type gene proportion and combining the mother genotype.

Provided herein, are compositions based on retroviruses (e.g., lentiviruses) comprising one or more nucleic acid molecules encoding retroviral Pol polyprotein components and a nucleic acid molecule comprising one or more transgene sequences flanked by long terminal repeat sequences, for delivery of the one or more transgenes to a target cell ex vivo or in vivo. The compositions are useful for delivering to a target cell (e.g., hematopoietic stem cells (HSCs), liver cells, ocular cells, muscle cells, epithelial cells, T cells, etc.) and / or stably expressing any transgene (e.g., beta-globin, Factor VIII, RP GTPase regulator (RPGR), dystrophin, cystic fibrosis transmembrane conductance regulator (CFTR), a chimeric antigen receptor, etc.) with a biological effect to treat and / or ameliorate the symptoms associated with any disorder related to gene expression (e.g., sickle cell disease, beta-thalassemia, haemophilia B, retinitis pigmentosa, Duchenne muscular dystrophy, cystic fibrosis, cancer, etc.).

Disclosed herein are methods of expanding hematopoietic stem cells (HSC) ex vivo and their uses thereof, the methods comprising administrating a radical trapping antioxidant (RTA) to the HSC isolated from a subject, wherein the RTA blocks ferroptosis in the HSC and increases HSC expansion. Also disclosed herein are methods of treating blood disorders, such as, for example, sickle cell disease or β-thalassemia. Further disclosed is a kit for use of HSC expansion.