40 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.

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.

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.

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.

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.

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 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.

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 present invention discloses a sgRNA, vector and application for editing βIVS-2-654 splicing mutation based on CRISPR / Cas9 technology. The nucleotide sequence thereof is shown in SEQ ID No: 1, SEQ ID No: 2 or SEQ ID No: 3. By microinjecting sgRNA and Cas9 mRNA into β 654 The gene-edited thalassemia mice were obtained from the fertilized eggs of thalassemia mice, in which the abnormal splicing of β-globin mRNA was corrected and the expression of β-globin was restored. 654 The hematological and pathological phenotypes of thalassemia mice were significantly improved. Therefore, the CRISPR system for repairing abnormal splicing has important clinical application value for the precise gene editing treatment of splicing abnormal single gene diseases.

The present disclosure provides a composition for treating hemoglobinopathy (e.g. sickle cell anemia, hemophilia, β-thalassemia, etc.). The present composition comprises a nuclease for modifying the BCL11A gene and a CRISPR-Cas system comprising a guide RNA. Also provided is a method for treatment by administering, in a subject with a hemoglobinopathy-related disease, a system that targets the BCL11A gene or a nucleic acid that encodes such a system.

Provided are an anti-human CD117 nanobody and use thereof. The nanobody comprises at least one VHH chain. The VHH chain comprises a CDR1, a CDR2, and a CDR3. The amino acid sequence of the CDR1 is set forth in SEQ ID NO: 4, the amino acid sequence of the CDR2 is set forth in SEQ ID NO: 5, and the amino acid sequence of the CDR3 is set forth in SEQ ID NO: 6; or the amino acid sequence of the CDR1 is set forth in SEQ ID NO: 7, the amino acid sequence of the CDR2 is set forth in SEQ ID NO: 8, and the amino acid sequence of the CDR3 is set forth in SEQ ID NO: 9; or the amino acid sequence of the CDR1 is set forth in SEQ ID NO: 10, the amino acid sequence of the CDR2 is set forth in SEQ ID NO: 11, and the amino acid sequence of the CDR3 is set forth in SEQ ID NO: 12. The use is use of the nanobody and a formulation thereof in the preparation of a drug for treating thalassemia. The nanobody has a good binding ability to CD117, and has the advantages of small molecular weight, high binding activity, low immunogenicity, easy modification, etc.

The subject matter described herein is directed to ferroportin inhibitor compounds of Formula I and pharmaceutical salts thereof, methods of preparing the compounds, pharmaceutical compositions comprising the compounds, and methods of administering the compounds for prophylaxis and / or treatment of diseases caused by a lack of hepcidin or iron metabolism disorders, particularly iron overload states, such as thalassemia, sickle cell disease and hemochromatosis, and also kidney injuries.

The present invention relates to a novel process for the preparation of compounds of formula (I) and pharmaceutically acceptable salts thereof, which are suitable for use as drugs for the prevention and / or treatment of diseases caused by hepcidin deficiency or iron metabolism disorders leading to increased iron levels or increased iron absorption, including iron overload, thalassemia, sickle cell disease and hemochromatosis.

The invention discloses application of a biomarker HMDB0254633 in detection of HBB gene mutation of macaque, relates to the technical field of biology, and solves the technical problem of lack of a specific biomarker for early detection of thalassemia intestinal complications caused by HBB mutation. The key points of the technical scheme are as follows: the invention provides application of the biomarker HMDB0254633 in preparation of a quantitative detection product for macaque HBB gene mutation, the chemical name of the biomarker HMDB0254633 is 3-oxooctadecanoic acid, the molecular formula of the biomarker HMDB0254633 is C18H34O3, the quantitative detection product is a reagent or a kit, and the invention further provides a method for quantitatively detecting HBB gene mutation. Comprising the following steps: 1) extracting metabolites in excrement; 2) detecting metabolites by using a quantitative detection product; the effects of providing a high-specificity non-invasive marker and a detection tool and realizing early-stage rapid and non-invasive detection are achieved.

The present invention discloses a method, product and application for gene editing of multiple genes in cells. The method includes the step of introducing an adenine base editor and at least one sgRNA into a cell; the at least one sgRNA includes any one, any two or all three of sgRNA1, sgRNA2 and sgRNA3, and the characteristics of the sgRNA1-3 are as described in the present invention. The present invention can utilize gene editing technology in combination with autologous hematopoietic stem cell transplantation to treat transfusion-dependent β-thalassemia (Transfusion-dependent β-thalassemia, TDT) and sickle cell disease (sickle cell disease, SCD). The technology used in the present invention has extremely high gene editing efficiency in hematopoietic stem / progenitor cells (HSPC), and the HSPCs edited by the gene can be differentiated into blood cells of each lineage after transplantation in vivo, rebuilding the hematopoietic system, while the expression of fetal hemoglobin in the red blood cells differentiated from the HSPCs edited by the gene is greatly improved, and the survival of the red blood cells in the body and the performance of normal physiological functions are also promoted.

The invention relates to a new process for preparing compounds of the formula (I) and pharmaceutically acceptable salts thereof, which act as ferroportin inhibitors being suitable for the use as medicaments in the prophylaxis and / or treatment of diseases caused by a lack of hepcidin or of iron metabolism disorders leading to increased iron levels or increased iron absorption, including iron overload, thalassemia, sickle cell disease and hemochromatosis.

The present invention discloses a multi-mode hemoglobin eluent and a method for measuring the same. The eluent includes eluent A, eluent B, eluent C, eluent E, eluent F, and eluent G for measuring hemoglobin. The raw materials of eluent A include 0.08-0.12 wt% of citric acid monohydrate, 0.40-0.50 wt% of tri-alkali metal citrate hydrate, 0.3-0.5 wt% of alkali metal perchlorate, and 0.01-0.04 wt% of sodium hydroxide. The present invention achieves the separation and measurement of multiple hemoglobin modes using a single eluent without requiring replacement of a chromatographic column stationary phase or mobile phase. The method can adapt to different hemoglobin measurement requirements, including conventional hemoglobin measurement, mutant hemoglobin measurement, and thalassemia-related hemoglobin measurement.