299 results about "Gene product" patented technology

Among other things, the present disclosure provides oligonucleotides, compositions, and methods thereof. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and / or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and / or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and / or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., knockdown ability, stability, delivery, etc. In some embodiments, the oligonucleotides decrease the expression, activity and / or level of a C9orf72 gene, including but not limited to, one comprising a repeat expansion, or a gene product thereof. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions, for example, in treatment of C9orf72-related disorders.

Aspects of the disclosure relate to methods of reducing expression or activity of DMPK (e.g., reducing the level of a mutant or wild-type DMPK RNA, or the activity of a DMPK gene product) and / or methods of treating myotonic dystrophy (e.g., DM1) in a subject. In some embodiments, the methods comprise administering to the subject a composition comprising complexes (e.g., muscle targeting complexes) comprising an oligonucleotide (e.g., a DMPK—targeting oligonucleotide) covalently linked to an antibody (e.g., anti-TfR1 antibody).

Provided herein are newly identified genes encoding proteins involved in herbicide detoxification processes in plants. It is demonstrated that these genes and their encoded proteins are involved in herbicide detoxification processes in plants and increased expression of these genes can increase herbicide tolerance in plants. Accordingly, methods for generating a plant with increased herbicide tolerance is provided, including gene-editing and transformation methods that increase the level of the one or more herbicide detoxification genes or gene products in plants. Also provided are the plants, seeds, plant cells, or plant parts generated by or during these methods.

The disclosure relates to compositions and methods for altering, e.g., enhancing, the expression of GCase proteins, whether in vitro and / or in vivo. Such compositions include delivery of an adeno-associated viral (AAV) particle. The compositions and methods of the present disclosure are useful in the treatment of subjects diagnosed with, or suspected of having Parkinson Disease or related condition resulting from a deficiency in the quantity and / or function of GBA gene product or associated with decreased expression or protein levels of GCase protein.

The present invention relates to the fields of therapy and drug delivery. More specifically, disclosed herein are therapeutic methods and pharmaceutical compositions for treating disorders of blood-tissue barrier-shielded organs that harbour substantive populations of post-mitotic neurons, such as the organs derived from neural tube that include the central nervous system and the eye. The disclosed methods and compositions involve localised administration into such organs of an effector component that targets an intracellular biological target, in combination with a saponin component that enhances effective uptake of the effector component into the cells and / or that enhances effective routing of the effector component inside the cells where the biological target is present. For example, the effector component can be an oligonucleotide therapeutic that is targeting a gene product associated with the disorder of the CNS and / or of the eye. Due to cellular uptake-stimulating and / or endosomal escape enhancing effects of the saponin component, the presented herein neuropharmaceutical and ophthalmic compositions for the localised administration into the CNS and / or into the eye, respectively, can be formulated with lower concentrations of the effector component and / or at lower volumes, which confers safety-benefits to the neurons and to the comfort of the patient.

The present invention relates to the fields of therapy and drug delivery. More specifically, disclosed herein are therapeutic methods and pharmaceutical compositions for treating disorders of the central nervous system. The disclosed methods and compositions involve localised administration into such organs of an effector component that targets an intracellular biological target, in combination with a saponin component that enhances effective uptake of the effector component into the cells and / or that enhances effective routing of the effector component inside the cells where the biological target is present. For example, the effector component can be an oligonucleotide therapeutic that is targeting a gene product associated with the disorder of the CNS. Due to cellular uptake-stimulating and / or endosomal escape enhancing effects of the saponin component, the presented herein neuropharmaceutical compositions for the localised administration into the CNS can be formulated with lower concentrations of the effector component and / or at lower volumes, which confers safety-benefits to the neurons and to the comfort of the patient.

Systems and methods for assessing microbiome-host interactions are described. Several microbial genera have been found to provide benefit for a variety of medical disorders and phenotypes. Microbial genera can be provided as a composition to provide a particular benefit. Microbial genera can be administered to an individual to alter expression of gene products such as cytokines. Microbial genera can be administered to an individual as a treatment for a medical disorder.

The present disclosure provides recombinant adeno-associated virus (AAV) virions with altered capsid protein, where the recombinant AAV (rAAV) virions exhibit greater ability to cross barriers between intravitreal fluid and retinal cells, and thus greater infectivity of a retinal cell compared to wild-type AAV, and where the rAAV virions comprise a heterologous nucleic acid. The present disclosure provides methods of delivering a gene product to a retinal cell in an individual.

Provided herein are methods and compositions for inducing parthenogenesis by expression in female gametophytes of a Babyboom (BBM) polynucleotide operably linked to a promoter expressed in an egg cell. Also included herein are promoters expressed in egg cells of plants and methods of using these promoters to express gene products in egg cells of plants.

A non-integrating viral delivery system is disclosed. The system includes a viral carrier, wherein the viral carrier contains a defective integrase gene; a heterologous viral episomal origin of replication; a sequence encoding at least one initiator protein specific for the heterologous viral episomal origin of replication, wherein expression of the sequence encoding the at least one initiator protein specific for the heterologous viral episomal origin of DNA replication is inducible; and at least one gene, gene product, shRNA, siRNA, miRNA, or other RNA of interest.

The present disclosure provides compositions and methods for altering auxin accumulation in corn or maize plants. Methods and compositions are also provided for altering the expression of genes related to auxin efflux through editing or mutagenesis of a brachytic2 (br2) gene to introduce a premature stop codon or a deletion into the gene such that a truncated Br2 protein encoded by the mutant allele of the br2 gene, which may be a dominant or semi-dominant allele, has at least part of a transmembrane domain without a nucleotide binding domain or motif. Modified plant, plant parts and cells having such a mutant allele with reduced or altered expression or activity of a br2 gene product can have improved characteristics, such as reduced plant height and increased lodging resistance, but without off-types in the plant.

Provided herein, in various embodiments, are methods of treating a fragile X-associated disorder (e.g., fragile X syndrome), comprising administering to a subject in need thereof, a therapeutically effective amount of an agent that decreases expression of an aberrant fragile X messenger ribonucleoprotein 1 (FMR1) gene product (e.g., FMR1-217). Also provided herein, in various embodiments, are compositions (e.g., polynucleotides such as antisense oligonucleotides or pharmaceutical compositions) for decreasing expression of an aberrant FMR1 gene product.

The present disclosure relates to computer-implemented methods and systems for identifying biosynthetic gene clusters (BGCs) that encode pathways for the production of secondary metabolites. Secondary metabolites that target genes or gene products that are homologous to, e.g., human genes or gene products may have utility as potential drug compounds.

In some aspects, cardiac-specific expression cassettes are provided herein. In some aspects, provided herein is an expression cassette comprising a polynucleotide sequence encoding a gene product for therapy of a heart disease, wherein the polynucleotide sequence is operably linked to promoter (e.g., a cardiac-specific promoter), and optionally an enhancer (e.g., a cardiac-specific enhancer). In some aspects, the disclosure provides recombinant adeno-associated virus (rAAV) virions, comprising a capsid protein and a viral genome comprising an expression cassette comprising a polynucleotide sequence encoding a therapeutic gene product, e.g., dwarf open reading frame (DWORF) polypeptide, operably linked to a promoter, the expression cassette flanked by inverted terminal repeats. The disclosure further provides pharmaceutical compositions and methods of treating or preventing heart disease.

The present disclosure relates to Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3 (SCA3), an autosomal dominantly inherited neurodegenerative disorder that is caused by an over-repetition of the polyglutamine-codifying region in the ataxin-3 (ATX7V3) gene. Expanded ATXN3 is prone to aggregate and disturbs diverse cellular systems, ultimately leading to cell dysfunction and death in specific neuronal populations. To date, no treatment able to reverse or stall MJD / SCA3 progression has been developed. Strategies based on the suppression of the deleterious gene products have demonstrated promising results in pre-clinical studies. Nonetheless, these strategies do not target the root cause of the disease, producing an incomplete and / or transient therapeutic effect in target cells or tissues. Recently, gene-based therapeutics, including the bacterial clustered regularly interspaced short palindromic repeat (CRISPR) systems for gene edition, have been successfully used to permanently inactivate and correct disease-related genes, holding promise for the development of a definitive cure for inherited diseases.

The invention belongs to the technical field of biology, and particularly relates to an overexpression IRF5 plasmid as well as a construction method and application thereof. The invention provides a construction method of a plasmid for overexpression of IRF5 in zebra fish. The method comprises the following steps: carrying out reverse PCR on an empty vector to prepare a first linearized empty vector; amplifying IRF5 by taking the WT zebra fish cDNA as a template to obtain a first target gene product; adding a homologous arm to the first target gene product to obtain a homologous arm product; performing homologous recombination on the homologous arm product and a first linearized empty vector to obtain a first homologous recombination product; taking the first homologous recombination product as a template, and carrying out PCR (Polymerase Chain Reaction) amplification to obtain an IRF5 gene product with a promoter, namely a second target gene product; performing reverse PCR on the empty vector to prepare a second linearized empty vector; and carrying out homologous recombination on the second target gene product and a second linearized empty vector to obtain the plasmid. According to the invention, the IRF5 is cloned into the vector through homologous recombination, and the recombinant vector constructed by the method can be used for culturing the zebrafish over-expressing the IRF5.

The present invention relates to the introduction of expression constructs encoding different gene products such as proteins or nucleic acids at defined ratios into host cell lines containing multiple dock sites for insertion of the nucleic acid construct, and to the production of proteins that require expression of at least two gene products.

Compositions and methods and for enhancing the resistance of plants, particularly wheat plants to stem rust caused by Puccinia graminis f. sp. tritici are provided. The compositions comprise nucleic acid molecules encoding resistance (R) gene products and variants thereof and plants, seeds, and plant cells comprising such nucleic acid molecules. The methods for enhancing the resistance of a plant to stem rust comprise introducing a nucleic acid molecule encoding an R gene product into a plant cell. Additionally provided are methods for using the resistant plants in agriculture to limit stem rust.

The invention relates generally to the THAP1 gene and mutations in this gene, as well as the THAP1 protein and mutations in this protein, that are associated with dystonia. The invention relates to the identification, isolation, cloning and characterization of the DNA sequence corresponding to the wild type and mutant THAP1 genes, as well as isolation and characterization of their transcripts and gene products. The invention further relates to methods and kits useful for detecting mutations in THAP1 that are associated with dystonia, as well as to methods and kits useful for diagnosing dystonia. The present invention also relates to therapies for treating dystonia, including gene therapeutics and protein / antibody based therapeutics.

The present disclosure relates to the introduction of expression constructs encoding different gene products such as proteins or nucleic acids at defined ratios into host cell lines containing multiple dock sites for insertion of the nucleic acid construct, and to the production of proteins that require expression of at least two gene products.

Described in certain example embodiments herein are engineered phages comprising one or more heterologous genes that encode one or more heterologous gene products and methods of using the engineered phages to deliver one or more heterologous gene products to a subject.

This invention relates to polynucleotides comprising UBE3A open reading frame (ORF) sequences, vectors comprising the same, and methods of using the same for delivery of the ORF to a cell or a subject and to treat disorders associated with aberrant expression of a UBE3A gene or aberrant activity of a UBE3A gene product in the subject, such as Angelman Syndrome.

The invention provides for a composition, which in particular comprising a fusion molecule comprising a least one DNA binding protein and at least one modulator of gene expression, wherein the fusion molecule is targeted to a genomic region near a VEGF gene and / or within a VEGF regulatory element and the at least one modulator of gene expression provides a modification of at least one nucleotide near the VEGF gene and / or within a VEGF regulatory element. The invention also provides methods of reduction or elimination of VEGF gene products in vivo and uses thereof.

The present disclosure provides adeno-associated virus (AAV) virions with altered capsid protein, where the AAV virions exhibit greater infectivity of retinal cells, when administered via intravitreal injection, compared to wild-type AAV. The present disclosure further provides methods of delivering a gene product to a retinal cell in an individual, and methods of treating ocular disease.

The present invention relates to compositions and methods for subpopulation-specific modulation of cell function and for treating repeat expansion disorders comprising genetic, degenerative, neurological and cellular diseases, including immune disorders. Also provided are research kits for subpopulation-specific modulation of protein activity and the corresponding potential to discover novel therapeutic compositions. More specifically, the disclosed compositions and methods selectively up- or downregulate at least a first population of a cellular protein or therapeutic target with minimal or negligible effect on the activity of at least a second population of the cellular protein or therapeutic target.

Aspects of the disclosure relate to compositions and methods useful for delivering minigenes to a subject. Accordingly, the disclosure is based, in part, on isolated nucleic acids and gene therapy vectors, such as viral (e.g., rAAV) vectors, comprising one or more gene fragments encoding a therapeutic gene product, such as a protein or peptide (e.g. a minigene). In some embodiments, the disclosure relates to gene therapy vectors encoding a USH1B protein (e.g. the gene product of USH1B, also referred to as MY07A) or a portion thereof. In some embodiments, compositions described by the disclosure are useful for treating diseases associated with mutations in the USH1B (MY07A) gene, for example Usher Syndrome.

The invention relates to a baculoviral vector system for improved delivery of DNA, RNA and protein into mammalian cells, including primary cells, tissues, and whole mammalian organisms.

The invention relates to allograft tolerance without systemic immune containment. There is provided a cell genetically modified to comprise at least one mechanism for providing localized immune containment at a transplantation site when transplanted into an allogeneic host; and methods for making and using the cells. The cell comprises a set of transgenes, each transgene encoding a gene product of cytoplasm, membrane binding or topical action, and having one or more of the following functions: mitigating antigen presenting cell activation and function; mitigating leukocyte activity or cytolytic function of the aggressive graft; the cytolytic function and phagocytosis of macrophages of allograft cells are reduced; inducing apoptosis in the graft-attacking leukocytes; reducing local inflammatory proteins; and protecting from leukocyte mediated apoptosis.

The present invention relates to a modified adeno-associated virus (AAV) capsid polypeptide and a novel recombinant adeno-associated virus (rAAV) comprising the modified AAV capsid polypeptide for delivering the gene product for the therapy. The present invention also relates to a pharmaceutical composition comprising the rAAV of the present invention, and a method of treating a retinal disease comprising the administration of the rAAV or the pharmaceutical composition of the present invention to an eye of a subject in need thereof.

The present invention relates to the field of therapy and drug delivery. More specifically, therapeutic methods and pharmaceutical compositions for treating disorders of blood-tissue barrier-protected organs that harbor substantial populations of postmittal neurons, such as organs derived from the neural tube, including the central nervous system and the eye. The disclosed methods and compositions involve topical administration of an effector component that targets intracellular biological targets to such organs, in combination with a saponin component that enhances the effective uptake of the effector component into cells and / or enhances the effective delivery of the effector component within cells where the biological target is present. For example, the effector component may be an oligonucleotide therapeutic that targets gene products associated with CNS and / or ocular disorders. Due to the cellular uptake stimulating and / or endosomal escape enhancing effects of the saponin component, the neuropharmaceuticals and ophthalmic compositions presented herein for topical administration to the CNS and / or eye, respectively, can be formulated with lower concentrations of the effector component and / or lower volumes, which provides safety benefits to neurons and patient comfort.