26 results about "Enzyme deficiency" patented technology

Provided herein are methods of inserting a nucleic acid encoding a polypeptide of interest into a target genomic locus in a cell or a population of cells in a subject, methods of expressing a polypeptide of interest from a target genomic locus in a cell or a population of cells in a subject, methods of treating an enzyme deficiency in a subject in need thereof, and methods of preventing or reducing the onset of a sign or symptom of an enzyme deficiency in a subject in need thereof. The methods use CD40 inhibitors (e.g., CD40 antigen-binding molecules) to mitigate immune response and facilitate redosing of nucleic acid constructs encoding a polypeptide of interest and nuclease agents targeting a target genomic locus to achieve, for example, a step-wise increase in expression of a polypeptide of interest in a subject following insertion of the nucleic acid construct without overshooting.

Provided herein are methods of inserting a nucleic acid encoding a polypeptide of interest into a target genomic locus in a cell or a population of cells in a subject, methods of expressing a polypeptide of interest from a target genomic locus in a cell or a population of cells in a subject, methods of treating an enzyme deficiency in a subject in need thereof, and methods of preventing or reducing the onset of a sign or symptom of an enzyme deficiency in a subject in need thereof. Some methods, such as when a subject has preexisting against an immunogen to be administered, use plasma cell depleting agents or combinations comprising plasma cell depleting agents to mitigate immune response and facilitate redosing of nucleic acid constructs encoding a polypeptide of interest and nuclease agents targeting a target genomic locus to achieve, for example, a step-wise increase in expression of a polypeptide of interest in a subject following insertion of the nucleic acid construct without overshooting. Other methods, such as when a subject has no preexisting immunity against an immunogen to be administered, use B cell depleting agents (e.g., anti-CD20xCD3 antibody or functional fragment thereof) to mitigate immune response and facilitate redosing of nucleic acid constructs encoding a polypeptide of interest and nuclease agents targeting a target genomic locus to achieve, for example, a step-wise increase in expression of a polypeptide of interest in a subject following insertion of the nucleic acid construct without overshooting.

To provide compositions and methods for regulating protein production in target cells. [Solution] The compositions and methods disclosed herein can improve diseases associated with protein or enzyme deficiency. The present invention provides, for example, a composition comprising (a) at least one mRNA molecule that is at least partly encoding a functionally secreted polypeptide, and (b) a transport vehicle comprising lipid nanoparticles. The present invention also provides a method for treating a subject deficient in a functional polypeptide, comprising administering a composition comprising (a) at least one mRNA that is at least partly encoding the functionally secreted polypeptide, and (b) a transport vehicle comprising lipid nanoparticles, wherein after administration of the composition, the mRNA is expressed in a target cell to produce the functionally secreted polypeptide.

The present disclosure describes compositions and methods for treating ornithine transcarbamylase (OTC) deficiency. The compositions include a lipid formulation and messenger RNA (mRNA) encoding an OTC enzyme. The lipid formulations can comprise an ionizable cationic lipid in a lipid nanoparticle encapsulating the mRNA.

This disclosure relates to mRNA therapy for the treatment of arginase deficiency (AD). mRNAs for use in the invention, when administered in vivo, encode arginase 1 (ARG1). mRNA therapies of the disclosure increase and / or restore deficient levels of ARG1 expression and / or activity in subjects. mRNA therapies of the disclosure further decrease abnormal accumulation of ammonia associated with deficient ARG1 activity in subjects.

The invention particularly discloses a medicine for treating hereditary liver diseases and application thereof, and relates to the technical field of gene therapy. The invention provides a lipid nanoparticle containing alanine glyoxylate aminotransferase mRNA (messenger Ribonucleic Acid). The lipid nanoparticle comprises an mRNA solution and a lipid mixed solution, the concentration ratio of the mRNA solution to the lipid mixed solution is 1: (20-120). According to the lipid nanoparticles provided by the invention, the problem that the parenchymal hepatic cell AGT enzyme of a patient with primary type 1 hyperoxaluria is deficient is solved, the AGT mRNA delivery efficiency is further improved, and the urine oxalate reduction effect of a protein replacement therapy is improved. The invention provides a theoretical basis and an experimental basis for developing a new treatment strategy, and has good clinical transformation and clinical application prospects.

The invention relates to the field of biotechnology, and more particularly to a pharmaceutical composition and a method for the prophylaxis and treatment of a lysosomal enzyme deficiency in a subject, which can be used in medicine. The present invention relates to an HIR-Fab-IDS compound that can be used for the prophylaxis or treatment of a lysosomal enzyme deficiency in a subject suffering from a lysosomal storage disease in the form of mucopolysaccharidosis type II (MPS II), wherein at least one dose of said HIR-Fab-IDS compound is administered to the subject in an amount of from 1 to 12 mg / kg, and further relates to a pharmaceutical composition for use in the prophylaxis or treatment of a lysosomal enzyme deficiency in a subject with the lysosomal storage disease MPS II, wherein the composition contains said HIR-Fab-IDS compound, as well as to a method for the prophylaxis or treatment of a lysosomal enzyme deficiency in a subject with the lysosomal storage disease MPS II, which includes administering at least one dose of said HIR-Fab-IDS compound to the patient.

The present invention relates to methods and compositions for editing an ASL polynucleotide, e.g., an ASL polynucleotide comprising a SNP associated with argininosuccinate lyase deficiency. The invention also relates to methods and compositions for treating or preventing argininosuccinate lyase deficiency in a subject.

Provided herein are methods of inserting a nucleic acid encoding a polypeptide of interest into a target genomic locus in a cell or a population of cells in a subject, methods of expressing a polypeptide of interest from a target genomic locus in a cell or a population of cells in a subject, methods of treating an enzyme deficiency in a subject in need thereof, and methods of preventing or reducing the onset of a sign or symptom of an enzyme deficiency in a subject in need thereof. Some methods, such as when a subject has preexisting against an immunogen to be administered, use plasma cell depleting agents or combinations comprising plasma cell depleting agents to mitigate immune response and facilitate redosing of nucleic acid constructs encoding a polypeptide of interest and nuclease agents targeting a target genomic locus to achieve, for example, a step-wise increase in expression of a polypeptide of interest in a subject following insertion of the nucleic acid construct without overshooting. Other methods, such as when a subject has no preexisting immunity against an immunogen to be administered, use B cell depleting agents (e.g., anti-CD20xCD3 antibody or functional fragment thereof) to mitigate immune response and facilitate redosing of nucleic acid constructs encoding a polypeptide of interest and nuclease agents targeting a target genomic locus to achieve, for example, a step-wise increase in expression of a polypeptide of interest in a subject following insertion of the nucleic acid construct without overshooting.

This disclosure pertains to codon-optimized GBA1 polynucleotides that encode a GCase protein, with a portion of the coding sequence deviating from the wild-type. Additionally, the disclosure encompasses expression constructs, vectors, viral particles, or compositions containing the disclosed polynucleotide. Furthermore, it encompasses methods and applications of these polynucleotides, expression constructs, vectors, viral particles, or compositions, including treatment of the disease or condition is associated with GCase deficiency.

The present invention relates to the field of biotechnology, and more particularly to pharmaceutical compositions and methods for preventing and treating lysosomal enzyme deficiency in a subject, which can be used in medicine. The present invention relates to an HIR-Fab-IDS compound which can be used to prevent or treat a lysosomal enzyme deficiency in a subject suffering from a lysosomal storage disease in the form of mucopolysaccharide storage disease type II (MPS II) wherein at least one dose of said HIR-Fab-IDS compound is administered to the subject in an amount of 1 to 12 mg / kg; and in addition to a pharmaceutical composition for the prevention or treatment of a lysosomal enzyme deficiency in a subject suffering from the lysosomal storage disease MPS II wherein the composition comprises said HIR-Fab-IDS compound; and to a method for preventing or treating a lysosomal enzyme deficiency in a subject suffering from the lysosomal storage disease MPS II comprising administering to the patient at least one dose of said HIR-Fab-IDS compound.

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 disclosure provides a modified human OTC protein having improved properties for the treatment of OTC deficiency in a patient. Preferably, the protein of the disclosure is produced from a codon optimized mRNA suitable for administration to a patient suffering from OTC deficiency wherein upon administration of the mRNA to the patient, the protein of the disclosure is expressed in the patient in therapeutically effective amounts to treat OTC deficiency. The present disclosure also provides codon optimized mRNA sequences encoding wild type human OTC comprising a 5′ UTR derived from a gene expressed by Arabidopsis thaliana for use in treating OTC deficiency in a patient.

This invention discloses a gene editing system for constructing porcine nuclear transplantation donor cells for a metoprolol reductase deficiency model with SPR gene mutations and its applications. The invention provides a kit comprising SPR-gRNA1 (SEQ ID NO: 16), SPR-gRNA4 (SEQ ID NO: 17), and NCN protein. The invention also provides a method for preparing recombinant cells: co-transfecting porcine cells with SPR-gRNA1, SPR-gRNA4, and NCN protein to obtain recombinant cells. The recombinant cells are recombinant cells with a mutated SPR gene. The kit is used for: preparing recombinant cells; preparing porcine metoprolol reductase deficiency models; and preparing metoprolol reductase deficiency cell models, tissue models, or organ models. This invention has significant application value for the development of drugs for metoprolol reductase deficiency and for elucidating the pathogenesis of this disease.

The present application provides a novel means for treating ornithine transcarbamylase deficiency. More specifically, the present application provides a modified adeno-associated virus vector which expresses ornithine transcarbamylase so that an attack from a neutralizing antibody in blood is reduced and a gene is efficiently introduced into a liver of a living body (for example, human). The present application provides, for example, a modified adeno-associated virus vector which expresses omithine transcarbamylase, which contains a modified VP1 protein that contains, for example, an amino acid sequence obtained by substituting at least one of the amino acids at positions 472, 587 and 706 in the amino acid sequence of the VP1 protein with another amino acid, and which does not cross-react with a neutralizing antibody against AAV2.

To provide a pharmaceutical combination for use in the treatment or the prophylaxis of a cancer, an autoimmune disease such as rheumatoid arthritis, an enzyme deficiency, a gene defect, a disease related 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, α-1 antitrypsin related liver disease, acute hepatic porphyria, or transthyretin-mediated amyloidosis.SOLUTION: A kit including a first pharmaceutical composition and a second pharmaceutical composition is provided. The first pharmaceutical composition includes a first conjugate including at least one effector molecule and a single-domain antibody (sdAb) for binding to a first cell-surface molecule. The second pharmaceutical composition includes a second conjugate including an antibody for binding to a second cell-surface molecule and a saponin.SELECTED DRAWING: None

The application discloses a 21-hydroxylase deficiency screening kit and application thereof, relates to the blood analysis technical field, and a steroid hormone marker composition of 21-hydroxylase deficiency, wherein the nine markers comprise 17alpha-hydroxyprogesterone, androstenedione, 11-deoxycortisol, 21-deoxycortisol, cortisol, corticosterone, progesterone, dihydrotestosterone and 11-deoxycorticosterone; the kit can be used for screening 21-hydroxylase deficiency, 11beta-hydroxylase deficiency, 17alpha-hydroxylase deficiency and other types of diseases; the kit comprises detection components for detecting the hormones; compared with a traditional time-resolved fluorescence immunoassay method, the LC-MS / MS multi-index combined detection scheme adopted in the application can significantly reduce false positive results; and invalid recall, unnecessary family anxiety and medical burden caused by false positive results are greatly reduced.

The present disclosure relates to compositions and methods for treating iron overload. In particular, the methods for treating iron overload include administering to a patient an HIV protease inhibitor and an iron chelator. Iron overload may occur in patients diagnosed with anemia from inflammation or from chronic disease including hemochromatosis, sickle cell disease, thalassemia, sideroblastic anemia, an enzyme deficiency, pre-operative anemia, a cardiovascular disease, atransferrinemia, or aceruloplasminemia.

The invention relates to multiple fluorescent quantitative PCR (Polymerase Chain Reaction) primers, a probe and a kit for detecting glucose-6-phosphate dehydrogenase deficiency G6PD (Glucose-6-phosphate dehydrogenase) gene variation sites. The invention provides three G6PD gene mutation sites found for the first time, and the three mutation sites are respectively a G6PD gene c.521Ggt, a G6PD gene c.521Ggt and a G6PD gene c.521Ggt. C, c, 661 Tgt, 661 Tgt; c, c, 680Ggt; c variation sites expand the pathogenic variation spectrum of the G6PD gene. The invention further provides a primer, a probe composition and a kit for detecting the G6PD gene variation site of the glucose-6-phosphate dehydrogenase deficiency disease. The primer, the probe composition and the kit are used for screening or diagnosing the glucose-6-phosphate dehydrogenase deficiency disease. The sequences of the primer and the probe are as shown in SEQ ID NO.1-10. The kit disclosed by the invention can comprehensively cover three new pathogenic variation sites of the G6PD gene related to the glucose-6-phosphate dehydrogenase deficiency, is high in accuracy and can specifically detect the pathogenic variation sites.

The present invention relates to 4-hydroxybenzoic acid for use thereof in the stimulation of mitochondrial metabolism from before fertilization and during subsequent embryonic development. The inventors have discovered that 4-hydroxybenzoic, administered orally before the moment of fertilization, induces an increase in coenzyme Q levels and mitochondrial metabolism in the brain of both a control mouse and a mouse with coenzyme Q deficiency due to mutation in the Coq2 gene. The present invention thereby allows the therapeutic use of 4-hydroxybenzoic acid for neurological, neurometabolic, neurodegenerative and cardiometabolic diseases, as well as cases of infertility, associated with coenzyme Q deficiency, mitochondrial dysfunction, impaired energy metabolism and / or increased oxidative stress. The present invention also relates to a pharmaceutical composition, to the non-therapeutic use of 4-hydroxybenzoic acid and to a nutraceutical composition or functional food, dietary product or nutritional supplement.

The present disclosure relates to methods for treating PMM2-CDG using an aldose reductase inhibitor. In other embodiments, the present disclosure relates to a method for treating PMM2-CDG in a subject in need thereof, comprising administering a therapeutically effective amount of a pharmaceutical composition comprising an AR inhibitor, such as a compound of any one of Formulas (I)-(VI), and a pharmaceutically acceptable carrier. The present disclosure relates to a method for increasing PMM2 enzyme activity in a subject having PMM2-CDG, comprising administering to the subject a therapeutically effective amount of an aldose reductase inhibitor, such as a compound of any one of Formulas (I)-(VI).

The present disclosure provides a modified human OTC protein having improved properties for the treatment of OTC deficiency in a patient. Preferably, the protein of the disclosure is produced from a codon optimized mRNA suitable for administration to a patient suffering from OTC deficiency wherein upon administration of the mRNA to the patient, the protein of the disclosure is expressed in the patient in therapeutically effective amounts to treat OTC deficiency. The present disclosure also provides codon optimized mRNA sequences encoding wild type human OTC comprising a 5′ UTR derived from a gene expressed by Arabidopsis thaliana for use in treating OTC deficiency in a patient.

The present invention relates to the field of biotechnology, and more particularly to pharmaceutical compositions and methods for the prevention and treatment of lysosomal enzyme deficiency in a subject, which may be used in medicine. The present invention relates to an HIR-Fab-IDS compound that may be used to prevent or treat lysosomal enzyme deficiency in a subject suffering from lysosomal storage disease in the form of mucopolysaccharidosis type II (MPS II), wherein at least one dose of the HIR-Fab-IDS compound is administered to the subject in an amount of 1 to 12 mg / kg, and to a pharmaceutical composition for use in the prevention or treatment of lysosomal enzyme deficiency in a subject with the lysosomal storage disease MPS II, the composition containing the HIR-Fab-IDS compound, and a method for preventing or treating lysosomal enzyme deficiency in a subject with the lysosomal storage disease MPS II, comprising administering to the patient at least one dose of the HIR-Fab-IDS compound.

The present invention is directed to compositions and methods for treating aromatic L-amino acid decarboxylase (AADC) deficiency. This invention includes a method of treating AADC deficiency in a pediatric subject, comprising the steps of: (a) providing a pharmaceutical formulation comprising an rAAV2-hAADC vector, (b) stereotactically delivering the pharmaceutical formulation to at least one target site in the brain of the subject in a dose of an amount at least about 1.8×1011 vg; wherein delivering the pharmaceutical formulation to the brain is optionally by frameless stereotaxy, and optionally wherein the dose is an amount of at least about 2.4×1011 vg and in some embodiments wherein the pharmaceutical formulation comprises a rAAV2-hAADC vector concentration of about 5.7×1011 vg / mL. This invention is also directed to methods for treating aromatic L-amino acid decarboxylase (AADC) deficiency, wherein the method optionally further comprises the step of administering a therapeutically effective dose of dopamine-antagonist to the subject such as risperidone. This invention is also directed to methods for treating aromatic L-amino acid decarboxylase (AADC) deficiency, wherein the method optionally comprises providing a pharmaceutical formulation comprising an rAAV2-hAADC vector, and empty capsids.

Provided are codon-optimized GBA1polynucleotides that encode a GCase protein, with a portion of the coding sequence deviating from the wild-type. Additionally provided are expression constructs, vectors, viral particles, or compositions containing the disclosed polynucleotide. Furthermore, provided are methods and applications of these polynucleotides, expression constructs, vectors, viral particles, or compositions, including treatment of the disease or condition which is associated with GCase deficiency.