156 results about "Gene product" patented technology

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).

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.

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 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 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.

Provided is a means for constructing a modified genomic DNA which has a nucleotide sequence different from an existing genomic DNA sequence, contains a modified gene capable of expressing a polypeptide, a functional RNA, or both, and does not contain exogenous DNA.　This method comprises: performing, at least twice, (a) a step for specifically cleaving genomic DNA of a cell into at least two target sequences by means of a sequence-specific nuclease, and linking the resultants through a DNA double-stranded cleavage repair by the cell; and deleting at least two regions from an existing gene and non-coding regions adjacent thereto to thereby produce a modified gene.

Plant cell fate and development is altered by treating cells with cellular reprogramming factors. Embryogenesis inducing embryogenesis factor genes and / or morphogenic developmental genes are used as cellular reprogramming factors, specifically comprising polypeptides or polynucleotides encoding gene products for generating doubled haploids or haploid plants from gametes. Maize microspores treated by contacting the isolated cells with an exogenous purified, recombinant embryogenesis inducing embryogenesis factor gene products and / or morphogenic developmental gene polypeptide results in embryogenesis. The gametes of a maize plant develop into embryoids when transformed with a genetic construct including regulatory elements and structural genes capable of acting in a cascading fashion to alter cellular fate of plant cells. Embryogenesis factor proteins and / or developmental morphogenic proteins expressed from a genetic construct are used for ex situ treatment methods and for in planta cellular reprogramming.

A method of direct transdifferentiation of somatic cells into other somatic cells may be convenient and still have good reproducibility, excellent production efficiency, and short performed time. Methods for direct transdifferentiation of somatic cells into other somatic cells may include: (a) introducing a GLIS family gene, a mutated GLIS family gene or a gene product thereof into somatic cells; and (b) culturing the gene-introduced somatic cells in a culture medium containing a component that induces differentiation of the somatic cells or precursor cells of the somatic cells into other somatic cells.

The application discloses a recombinant T cell with a knocked-out STARD7 gene and an application thereof, relates to the technical field of immune cells, and discloses that the recombinant T cell does not contain a functional STARD7 gene, or a biological function of a STARD7 gene product of the recombinant T cell is inhibited. In the application, the STARD7 is knocked out in T cells by means of CRISPR-Cas9 gene editing in an early stage of acute infection of mice, differentiation of SLECs is significantly damaged, and the proportion and quantity of MPECs are increased to a certain extent; therefore, the knockout of the STARD7 can be used as a treatment method for increasing the quantity of MPECs and regulating immune cells, so as to resist acute infection caused by external pathogens and promote the maintenance of memory cells existing in the body for a long time.

The application provides application of Brassica napus gene BnDTX19 in sclerotinia prevention and control, and is obtained by creating transgenic rapeseed to change the disease resistance of rapeseed material. The application constructs the super-expression and RNAi transgenic rapeseed of BnDTX19, firstly discloses the positive regulation function of the gene on sclerotinia resistance, provides the application of the BnDTX19 gene in obtaining high-sclerotinia-resistant rapeseed material by creating super-expression rapeseed, and the application of the BnDTX19-RNAi rapeseed in obtaining sclerotinia-resistant rapeseed material with weakened sclerotinia resistance. The BnDTX19 gene product provided by the application has the function of transporting the key pathogenic factor oxalic acid of sclerotinia to promote disease resistance, and is a new gene resource suitable for creating and breeding new sclerotinia-resistant rapeseed materials and new varieties.

An extracellular vesicle based therapeutic compound for treating tumors and cancers. The extracellular vesicle based therapeutics use exosomes that are transdifferentiation-derived induced neural stem cells (Exo-iNSCs) that produce an extracellular vesicle having a tumoricidal gene product or an anti-cancer molecule withing the extracellular vesicle. The therapeutic agent is present in a lumen of the extracellular vesicle or is distributed across a membrane surface of the extracellular vesicle. Methods of using the extracellular vesicle based therapeutic compounds are effective in treating tumors and cancers.

Provided are methods for rapid multiplex HLA genotyping and transcript quantitation. In some embodiments, the presently disclosed methods include providing a. sample from the cell, tissue, or organ that has mRNA derived from an HLA gene product; reverse transcribing the mRNA to produce a. pool of cDNAs; amplifying the cDNAs that result from reverse transcription of HLA-specific mRNAs to produce a pool of HLA-specific cDNAs; and determining the sequence of each HLA-specific cDNAs, whereby the HLA status of the cell, tissue, organ, or subject is determined. Also provided are methods for genotyping donor cells, tissues, and / or organs meant for transplantation into recipients. In some embodiments, the methods can be used to identify the presence of absence of each of HLA-A, -B, -C, -DRB 1 / 3 / 4 / 5, -DQA1, and -DQB1 in a biological sample.

Disclosed herein are novel Pichia pastoris strains for expression of exogenous proteins with substantially homogeneous N-glycans. The strains are genetically engineered to include a mutant OCH1 allele which is transcribed into an mRNA coding for a mutant OCH1 gene product (i.e., α-1,6-mannosyltransferase, or “OCH1 protein”). The mutant OCH1 protein contains a catalytic domain substantially identical to that of the wild type OCH1 protein, but lacks an N-terminal sequence necessary to target the OCH1 protein to the Golgi apparatus. The strains disclosed herein are robust, stable, and transformable, and the mutant OCH1 allele and the ability to produce substantially homogeneous N-glycans are maintained for generations after rounds of freezing and thawing and after subsequent transformations.

To provide means for constructing a modified DNA having a nucleotide sequence different from an existing genome DNA sequence, which is a modified genome DNA including a modified gene in which polypeptide, functional RNA or both can be expressed, but not including a foreign DNA.SOLUTION: A method includes (a) performing a step of cleaving a genome DNA of a cell in at least two target sequences more specifically by a sequence-specific nuclease, and connecting them by DNA double-strand break repair by a cell at least twice, deleting at least two regions from an existing gene and its adjacent non-encoded region to create a modified gene.SELECTED DRAWING: Figure 1A

The present invention relates to the field of therapy and drug delivery. More specifically, disclosed herein are therapeutic methods and pharmaceutical compositions for treating disorders of blood tissue barrier shielded organs having a large number of populations of post-mitotic neurons, such as organs derived from neural tubes, including the central nervous system and the eye. The disclosed methods and compositions involve topically applying into such organs a combination of an effector component that targets a biological target in a cell, and a saponin component that promotes effective ingestion of the effector component into the cell and / or enhances effective path steering of the effector component within the cell in which the biological target is present. For example, the effector component may be an oligonucleotide therapeutic agent targeting gene products associated with CNS and / or disorders of the eye. Due to the cellular uptake stimulating effect and / or endosomal escape enhancing effect of the saponin component, the neuropharmaceutical and ophthalmic compositions presented herein for topical administration into the CNS and / or eye, respectively, may be formulated with lower concentrations of effector components and / or in smaller volumes, this brings safety benefits to the neurons and the comfort of the patient.

A method for producing pancreatic endocrine cells, including introducing (B) or (D) below into cultured somatic cells to transdifferentiate into a population of pancreatic endocrine cells that include insulin-producing beta-cells: (B) a GLIS1 gene or one or more gene products thereof, a Neurogenin3 gene or one or more gene products thereof, and a Pdx1 gene or one or more gene products thereof; and (D) a GLIS1 gene or one or more gene products thereof, a Neurogenin3 gene or one or more gene products thereof, and a MafA gene or one or more gene products thereof. The GLIS1 gene includes the nucleotide sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 2. The population of pancreatic endocrine cells are produced without undergoing an iPS cell stage.

The present invention is in the field of viral immunotherapy. The invention provides 1) an efficient recombinant poxvirus expressing a toxic conditional gene product that affects the viability of the recombinant poxvirus itself if left unregulated, or 2) a recombinant poxvirus expressing a conditional gene product with an improved safety profile, a method of producing them, a composition comprising them and therapeutic uses related thereto.

Methods for the fermentative production of O-phosphoserine, cysteate, or taurine in microbes or unicellular organisms that contain a serB mutation that either decreases serB expression, reduces the amount of the serB gene product or results in a serB gene product with low enzymatic activity. Genetic modifications of the O-phosphoserine, cysteate, or taurine and / or substrate biosynthetic pathways in unicellular organisms that include bacteria, algae, microalgae, diatoms, yeast, or fungi are disclosed. Also disclosed are fermentation and processing methods for the production of various O-phosphoserine-, cysteate-, or taurine-containing products and the use of the cells, fermentation broth or extracts that contain O-phosphoserine, cysteate, or taurine to produce products for use in food, feed, beverages, dietary and health supplements, cosmetics, personal care, pharmaceuticals, agricultural production, or surfactants.

The present disclosure provides recombinant adeno-associated virus (AAV) virions with altered capsid protein, where the recombinant AAV (rAAV) virions exhibit greater infectivity of a central nervous system (CNS) cell, compared to wild-type rAAV, and where the rAAV virions comprise a heterologous nucleic acid. The present disclosure provides methods of delivering a gene product to a CNS cell in an individual.

The invention is characterized by a method and application of codon optimization of a gene product. Specifically, the present disclosure features a codon optimization method that promotes the increase in mRNA half-life and stability by reducing the frequency of m6A modification, thereby achieving the purpose of improving protein production. Additional methods of delivering codon optimized gene products are disclosed. The methods of the present disclosure are clinically related to gene and cell therapy as well as vaccine development.

The present invention provides the use of an antigen-binding molecule that binds to HER3 for the treatment or prevention of a HER3-related cancer wherein the HER3-related cancer does not comprise a genetic variation that results in an increase in MET expression or an increase in gene product activity.

Provided is a method for production by direct transdifferentiation of somatic cells into another somatic cells which is convenient, has good reproducibility, is excellent in production efficiency, and is performed in a short period of time. The method for production by direct transdifferentiation of somatic cells into another somatic cells comprises: (a) a step of introducing a GLIS family gene, a mutated GLIS family gene or a gene product thereof into somatic cells; and (b) a step of culturing the gene-introduced somatic cells in a culture medium containing a component that induces differentiation of the somatic cells or precursor cells of the somatic cells into another somatic cells.

The invention belongs to the technical field of enzyme catalytic conversion number prediction, and discloses an enzyme catalytic conversion number prediction method and system based on function annotation and a hierarchical structure, and the prediction method comprises the steps: extracting protein unique identifier information based on a protein resource database, analyzing protein dynamic information and gene ontology functions according to the unique identifier information, and obtaining a prediction result; obtaining a relation table of the gene ontology and the enzymatic conversion coefficient; combining the hierarchical structure of the gene ontology with the relation table, capturing the mutual relation between the gene and the gene product, and constructing a hierarchical total tree between the gene ontology and the enzymatic conversion coefficient according to a relation capturing result; and extracting target gene ontology information according to the gene code of the target object, and matching an enzymatic conversion coefficient corresponding to the target gene ontology information from the hierarchical total tree as an enzymatic conversion number prediction result. According to the invention, gene and protein function annotations are provided by using the gene ontology, so that the function similarity of enzymes can be measured based on the gene ontology, and the enzymatic conversion value of unknown enzymes is speculated.

Provided herein are methods of hypoimmunogenicity, such as bioengineering methodologies and materials, including hypoimmunogenicity (such as engineering hypoimmunogenicity) methodologies and materials useful in, for example, genetically modifying and / or otherwise altering at least one target gene or gene product, processes for producing engineered hypoimmunogenic cells, manufacturing of engineered hypoimmunogenic cellular compositions, and uses thereof.

Aspects of the disclosure relate to compositions and methods for delivering a transgene (e.g., a transgene encoding one or more gene products) to a target cell (e.g., a brain cell). The disclosure is based, in part, on adeno-associated virus (AAV) capsid proteins comprising one or more amino acid substitutions, and methods of using the same for delivery of a transgene to tissues and cells of the central nervous system (e.g., brain cells).

Disclosed herein are novel Pichia pastoris strains for expression of exogenous proteins with substantially homogeneous N-glycans. The strains are genetically engineered to include a mutant OCH1 allele which is transcribed into an mRNA coding for a mutant OCH1 gene product (i.e., α-1,6-mannosyltransferase, or “OCH1 protein”). The mutant OCH1protein contains a catalytic domain substantially identical to that of the wild type OCH1 protein, but lacks an N-terminal sequence necessary to target the OCH1 protein to the Golgi apparatus. The strains disclosed herein are robust, stable, and transformable, and the mutant OCH1 allele and the ability to produce substantially homogeneous N-glycans are maintained for generations after rounds of freezing and thawing and after subsequent transformations.

This disclosure provides replication-incompetent adenoviral vectors useful in vaccine development and gene therapy. The disclosed vectors comprise a selective deletion of E3 and are particularly useful for preparation of vaccines development and for gene therapy using toxic transgene products that result in vector instability that occurs when the entire E3 domain is deleted.