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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Форма поиска

Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 24358. Отображено 100.
05-01-2012 дата публикации

Animal model for parkinson's disease

Номер: US20120005765A1
Принадлежит: St Louis University

Disclosed are methods and compositions for an animal model of Parkinson's disease. In particular, disclosed is the use of antisense compounds to inhibit the expression of ALDH1A1 in the substantia nigra of an animal brain for the purpose of creating an animal that will displays the symptoms of a human with Parkinson's Disease, including various biochemical, histological, and behavioral characteristics. Also disclosed are methods for using the animal model for Parkinson's disease to test potential therapeutic agents for Parkinson's disease.

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12-01-2012 дата публикации

Novel uses of vegfxxxb

Номер: US20120010138A1
Принадлежит: University of Bristol

The invention provides VEGF xxx b, or an agent which selectively promotes the expression of VEGF xxx b in preference to VEGF xxx in cells of a subject or in vitro, or an expression vector system which causes the expression of the VEGF xxx b in a host organism, for use in treating or preventing microvascular hyperpermeability disorders, or in regulating the pro-angiogenic pro-permeability properties of VEGF xxx isoforms, or in supporting epithelial cell survival without increased permeability, or in reducing the nature (for example the number density and/or size) of fenestrations of epithelial filtration membranes in vivo or in vitro.

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09-02-2012 дата публикации

Method for observing gad67-positive cell in transgenic animal

Номер: US20120036588A1
Автор: Yuchio Yanagawa
Принадлежит: JAPAN SCIENCE AND TECHNOLOGY AGENCY

A method for observing glutamate decarboxylase 67-positive cells in a transgenic mouse includes providing the transgenic mouse in which a nucleic acid sequence encoding green fluorescent protein is inserted in a frame within exon 1 of an endogenous glutamate decarboxylase 67 gene, whereby the transgenic mouse is capable of a functional expression of the green fluorescent protein in place of the endogenous glutamate decarboxylase 67 gene. Then, the glutamate decarboxylase 67-positive cells which are specifically visualized by the expression of the green fluorescent protein can be observed. The method may further include analyzing a function or morphology of the GABAergic neurons based on the observation of the glutamate decarboxylase 67-positive cells where the glutamate decarboxylase 67-positive cells are specifically visualized corresponding to a cell distribution of GABAergic neurons.

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16-02-2012 дата публикации

Human monoclonal antibody against a costimulatory signal transduction molecule ailim and pharmaceutical use thereof

Номер: US20120039874A1
Принадлежит: Japan Tobacco Inc

Immunization of human antibody-producing transgenic mice, which have been created using genetic engineering techniques, with AILIM molecule as an antigen resulted in various human monoclonal antibodies capable of binding to AILIM and capable of controlling a variety of biological reactions (for example, cell proliferation, cytokine production, immune cytolysis, cell death, induction of ADCC, etc.) associated with AILIM-mediated costimulatory signal (secondary signal) transduction. Furthermore, it has been revealed that the human monoclonal antibody is effective to treat and prevent various diseases associated with AILIM-mediated costimulatory signal transduction, being capable of inhibiting the onset and/or advancement of the diseases.

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08-03-2012 дата публикации

Anti- integrin antibodies, compositions, methods and uses

Номер: US20120058128A1
Принадлежит: Janssen Biotech Inc

The present invention relates to at least one novel anti-alpha-V subunit antibodies, including isolated nucleic acids that encode at least one anti-alpha-V subunit antibody, alpha-V subunit, vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.

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15-03-2012 дата публикации

Psca: prostate stem cell antigen and uses thereof

Номер: US20120063999A1
Принадлежит: Agensys Inc, UNIVERSITY OF CALIFORNIA

The invention provides a novel prostate cell-surface antigen, designated Prostate Stem Cell Antigen (PSCA), which is widely over-expressed across all stages of prostate cancer, including high grade prostatic intraepithelial neoplasia (PIN), androgen-dependent and androgen-independent prostate tumors.

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15-03-2012 дата публикации

Methods of Diagnosing Hypophosphatemic Disorders

Номер: US20120064544A1

The present invention relates to methods of diagnosing hypophosphatemic disorders.

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22-03-2012 дата публикации

Prevention and treatment of blood coagulation-related disases

Номер: US20120073002A1
Принадлежит: Chugai Pharmaceutical Co Ltd

Provided herein is an animal having a persistent hypercoagulable state by implanting a cell, for example a tumor cell, in which the gene of human tissue factor is implanted to an experimental animal such as a mouse and then growing the cell, thereby persistently supplying human tissue factor to the experimental animal. This animal model is useful for research and development of therapeutic agents for diseases having a persistent hypercoagulable state. Also provided are preventive or therapeutic agents for diseases having a persistent hypercoagulable state, a hypercoagulable state resulting from infections, venous thrombosis, arterial thrombosis, and diseases resulting from the hypertrophy of vascular media, the agent comprising an antibody against human tissue factor (human TF) as an active ingredient.

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05-04-2012 дата публикации

Sex-determination and methods of specifying same

Номер: US20120084873A1
Принадлежит: Individual

The present invention relates generally to the field of sex determination of animals. Provided are methods and agents to manipulate sex determination, particularly in avian animals such as chickens, through a male chromosome-linked testis (sex) regulatory gene. Expression or activity of the DMRT1 gene or protein is modulated to produce animals with displaying a phenotype sex that differs from their genotype.

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12-04-2012 дата публикации

Compositions comprising female germline stem cells and methods of use thereof

Номер: US20120087898A1
Принадлежит: General Hospital Corp

The present invention relates to female germline stem cells and their progenitors, methods of isolation thereof, and methods of use thereof.

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12-04-2012 дата публикации

Immunocompromised Ungulates

Номер: US20120090039A1
Принадлежит: Individual

Porcine animals, tissue and organs as well as cells and cell lines derived from such animals are provided that lack functional endogenous immunoglobulin loci and are deficient in immunoglobulin expression and B-cells. These animals are useful as model systems for research and for development of new pharmaceutical and biological agents. In addition, methods are provided to prepare such animals.

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19-04-2012 дата публикации

Boosting human dendritic cell development, homeostasis and function in xenografted immunodeficient mice

Номер: US20120094312A1

The present invention relates to a transgenic animal mode system based on the development of transgenic mice bearing components of the human immune system. Specifically, the Invention relates to a Flk2 deficient Rag “γc” transgenic mouse and the engraftment of said mouse with human hematopoietic stem cells. The present invention further presides methods for increasing the numbers of functionally competent human dendritic cells is and the hematopoietic targets cells that they interact with in said transgenic mouse through the administration of Flk2L. The transgenic animal model system of the invention may be used for testing human vaccine candidates, for screening potential Immune adjuvants and for developing novel therapeutics.

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19-04-2012 дата публикации

Class ii human histone deacetylases, and uses related thereto

Номер: US20120094862A1
Принадлежит: Harvard College

The invention provides histone deacetylase class II nucleic acids and polypeptides, methods and reagents for their use, and related compounds including small molecule libraries containing class II histone deacetylase inhibitors.

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19-04-2012 дата публикации

Mice That Make VL Binding Proteins

Номер: US20120096572A1
Принадлежит: Regeneron Pharmaceuticals Inc

Genetically modified mice and methods for making an using them are provided, wherein the mice comprise a replacement of all or substantially all immunoglobulin heavy chain V gene segments, D gene segments, and J gene segments with at least one light chain V gene segment and at least one light chain J gene segment. Mice that make binding proteins that comprise a light chain variable domain operably linked to a heavy chain constant region are provided. Binding proteins that contain an immunoglobulin light chain variable domain, including a somatically hypermutated light chain variable domain, fused with a heavy chain constant region, are provided. Modified cells, embryos, and mice that encode sequences for making the binding proteins are provided.

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10-05-2012 дата публикации

Human antibodies derived from immunized xenomice

Номер: US20120117669A1
Принадлежит: Abgenix Inc

Fully human antibodies against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.

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17-05-2012 дата публикации

Rna sequence-specific mediators of rna interference

Номер: US20120122111A1
Принадлежит: Individual

The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response. This specific targeting of a particular gene function is useful in functional genomic and therapeutic applications.

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17-05-2012 дата публикации

Dhx36 / rhau knockout mice as experimental models of muscular dystrophy

Номер: US20120124682A1
Принадлежит: Individual

The present invention provides a genetically-modified non-human animal whose somatic and germ cells contain a gene encoding an altered form of an DHX36 gene, the altered DHX36 haviang been targeted to replace a wild-type DHX36 gene into the animal or an ancestor of the animal at an embyonic stage using embryonic stem cells. An ideal use of the genetically-modified non-human animal of the invention is the use as an experimental model for muscular dystrophy, e.g. spinal muscular atrophy, to identify e.g. new treatments for muscular dystrophy and or study its pathogenesis.

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05-07-2012 дата публикации

Novel PRO1199 gene disruptions, and methods relating thereto

Номер: US20120174239A1
Принадлежит: Individual

The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO224, PRO9783, PRO1108, PRO34000, PRO240, PRO943, hu A33, PRO230, PRO178, PRO1199, PRO4333, PRO1336, PRO19598, PRO1083, hu TRPM2 or PRO1801 genes. Such in vivo studies and characterizations may provide valuable identification and discovery of therapeutics and/or treatments useful in the prevention, amelioration or correction of diseases or dysfunctions associated with gene disruptions such as neurological disorders; cardiovascular, endothelial or angiogenic disorders; eye abnormalities; immunological disorders; oncological disorders; bone metabolic abnormalities or disorders; lipid metabolic disorders; or developmental abnormalities.

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12-07-2012 дата публикации

Characterization of granulocytic ehrlichia and methods of use

Номер: US20120178102A1
Принадлежит: Antigenics LLC

The present invention relates, in general, to granulocytic ehrlichia (GE) proteins. In particular, the present invention relates to nucleic acid molecules coding for GE S2, S7, S22, S23, C6.1, C6.2, S11, E8, E46#1, and E46#2 proteins; purified GE S2, S7, S22, S23, C6.1, C6.2, S1, E8, E46#1, and E46#2 proteins and polypeptides; recombinant nucleic acid molecules; cells containing the recombinant nucleic acid molecules; antibodies having binding affinity specifically to GE S2, S7, S22, S23, C6.1, C6.2, S1, E8, E46#1, and E46#2 proteins and polypeptides; hybridomas containing the antibodies; nucleic acid probes for the detection of nucleic acids encoding GE S2, S7, S22, S23, C6.1, C6.2, S11, E8, E46#1, and E46#2 proteins; a method of detecting nucleic acids encoding GE S2, S7, S22, S23, C6.1, C6.2, S11, E8, E46#1, and E46#2 proteins or polypeptides in a sample; kits containing nucleic acid probes or antibodies; bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess, or prognose a mammal afflicted with ehrlichiosis; therapeutic uses, specifically vaccines comprising S2, S7, S22, S23, C6.1, C6.2, S11, E8, E46#1, and E46#2 proteins or polypeptides or nucleic acids; and methods of preventing or inhibiting ehrlichiosis in an animal.

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12-07-2012 дата публикации

Transgenic mouse model for developing enzyme replacement therapy for iduronate-2-sulfatase deficiency syndrome

Номер: US20120180148A1
Автор: Thong-Gyu Jin
Принадлежит: GCBIO CORP

The present invention relates to a transgenic mouse model for developing enzyme replacement therapy for iduronate-2-sulfatase deficiency syndrome, for example, Hunter syndrome. More specifically, the present invention relates to a transgenic mouse to be used for developing enzyme replacement therapy for iduronate-2-sulfatase, wherein the immune response against injected enzyme, such as, recombinant iduronate-2-sulfatase has been minimized in transgenic mouse model in the course of treating in vivo iduronate-2-sulfatase replacement.

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12-07-2012 дата публикации

Double mutant mouse and cell lines

Номер: US20120180149A1
Автор: Timothy A. Lyerla
Принадлежит: CLARK UNIVERSITY

A mutant transgenic mouse and cell line derived from the mouse are disclosed. The mutant transgenic mouse was developed from a cross between a mutant mouse which carries mutant genes that express a phenotype similar to human Hermansky-Pudlak Syndrome, and a mouse strain containing a transgene encoding a temperature sensitive protein that is inactive at physiological temperatures. The resulting mutant mouse is characterized by the presence of the HPS mutations as well as the transgene. The mutant mouse and cell lines derived from the lung tissue of the mouse are useful models for lung pathology associated with human HPS, lung fibrosis and inflammation. Methods and assays utilizing the cell lines also are disclosed.

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19-07-2012 дата публикации

Pnmt as a novel marker for progenitor cells

Номер: US20120183528A1
Принадлежит: Individual

In certain aspects, the present invention provides methods and compositions relating to a Pnmt-positive progenitor cell. In certain aspects, the present invention relates to methods for isolating and transplanting the subject progenitor cells, and methods for treating diseases such as myocardiac injuries and neurodegenerative disorders.

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02-08-2012 дата публикации

Ubiquitin interacting motif peptides as cancer therapeutics

Номер: US20120197059A1
Автор: HONG Chen, Yunzhou DONG
Принадлежит: Oklahoma Medical Research Foundation

The present invention involves the use peptides comprising ubiquitin interacting motifs (UIMs) alone or in combination with other agents to treat diseases involving neovascularization, such as cancer.

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09-08-2012 дата публикации

Drg11-responsive (dragon) gene family

Номер: US20120204280A1
Принадлежит: General Hospital Corp

This invention features methods and compositions useful for treating and diagnosing diseases of the nervous system, retina, skin, muscle, joint, and cartilage using a Dragon family protein. Protein and nucleic acid sequences of human, murine, zebrafish, and C. elegans Dragon family members are also disclosed.

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23-08-2012 дата публикации

Methods for protecting dopaminergic neurons from stress and promoting proliferation and differentiation of oligodendrocyte progenitors by nrg-2

Номер: US20120214737A1
Автор: Mark Marchionni
Принадлежит: Acorda Therapeutics Inc

The invention features methods of treatment and diagnosis using NRG-2 polypeptides, nucleic acid molecules, and antibodies. The invention also provides novel NRG-2 polypeptides and nucleic acid molecules.

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30-08-2012 дата публикации

Composition comprising rna derived from lactic acid bacterium as effective component

Номер: US20120220760A1

A composition has an immunomodulation action, and comprises an RNA derived from a lactic acid bacterium as an effective component. Alternatively, a composition has a cytokine production-modulating action, and includes an RNA derived from a lactic acid bacterium as an effective component.

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30-08-2012 дата публикации

Genetically modified animals and methods for making the same

Номер: US20120222143A1
Принадлежит: Recombinetics Inc

Compositions and methods for use of TALENs to make genetically modified livestock are set forth. The methods may include reporters for selecting cells or embryos that have been modified by TALENs for use as progenitor cells to make founder animals.

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13-09-2012 дата публикации

Method for preparing a transgenic animal of simultaneous multiple-gene expression

Номер: US20120233717A1
Принадлежит: Institute of Animal Science of CAAS

A method for preparing a transgenic animal of simultaneous multiple-gene expression is provided. Additionally, a method for preparing a transgenic embryo, which introduces both phytase gene and human myxovirus resistant gene A into a target embryo, to obtain a transgenic embryo is provided. The transgenic animal of simultaneous multiple-gene expression can be achieved by transplanting the transgenic embryo into the body of a female target animal. A significant advantage of the foregoing methods, among many others, exists in that the simultaneous expression of multiple genes can be achieved in one transgenosis, which provides a convenient mean for the preparation of combined-gene transferred animals etc.

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04-10-2012 дата публикации

Inducible small rna expression constructs for targeted gene silencing

Номер: US20120255045A1

The invention relates to vectors for the inducible expression of RNA molecules in eukaryotic, particularly mam

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11-10-2012 дата публикации

Expression of secreted human alpha-fetoprotein in transgenic animals

Номер: US20120259093A1
Принадлежит: Merrimack Pharmaceuticals Inc

The invention features a process of expressing secreted recombinant human alpha-fetoprotein (rHuAFP) in the milk or urine of transgenic mammals.

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25-10-2012 дата публикации

Method for constructing chimeric rat using rat embryonic stem cells

Номер: US20120272349A1

The present invention provides a preparation method of a chimeric embryo and a chimeric rat, which is characterized by contacting a rat pluripotent stem cell and a host embryo in the presence of an ES cell differentiation inhibitor. The method includes (a) a step for contacting a fertilized host embryo collected from a female rat and a rat pluripotent stem cell in the presence of an ES cell differentiation suppressant, and (b) a step for culturing the host embryo in contact with the rat pluripotent stem cell to form a chimeric embryo.

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01-11-2012 дата публикации

Homologous recombination in the oocyte

Номер: US20120276537A1
Принадлежит: Individual

The present invention relates to a method of modifying a target sequence in the genome of a mammalian or avian oocyte by homologous recombination with a donor nucleic acid sequence, the method comprising the steps (a) introducing into the oocyte a zinc finger nuclease or a nucleic acid molecule encoding the zinc finger nuclease in expressible form, wherein the zinc finger nuclease specifically binds within the target sequence and introduces a double strand break within the target sequence; and (b) introducing a nucleic acid molecule into the oocyte, wherein the nucleic acid molecule comprises the donor nucleic acid sequence and regions homologous to the target sequence. The present invention further relates to a method of producing a non-human mammal or an avian carrying a modified target sequence in its genome.

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01-11-2012 дата публикации

Transgenic animal overexpressing luciferase and preparation method thereof

Номер: US20120278911A1
Принадлежит: SNU R&DB FOUNDATION

The present disclosure provides a vector comprising a promoter and a luciferase gene having a nucleic acid sequence as disclosed in SEQ ID NO: 1; a fertilized egg transformed with the present vector; and a transgenic non-human animal overexpressing a luciferase gene from the vector and a method for preparing it. The vector and the animal of the present disclosure have a high expression rate for the luciferase gene, which confers high sensitivity for detection and thus useful for imaging analysis in a variety of research areas.

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15-11-2012 дата публикации

Regulation of t cell-mediated immunity by tryptophan

Номер: US20120288472A1
Автор: Andrew Mellor, David Munn
Принадлежит: GEORGIA HEALTH SCIENCES UNIVERSITY

A mechanism of macrophage-induced T cell suppression is the selective elimination of tryptophan and/or increase in one or more tryptophan metabolites within the local macrophage microenvironment Expression of IDO can serve as a marker of suppression of T cell activation, and may play a significant role in allogeneic pregnancy and other types of transplantation. Inhibitors of IDO can be used to activate T cells. Inhibiting tryptophan degradation, or supplementing tryptophan concentration, can be used in addition to, or in place of, inhibitors of IDO. Increasing tryptophan degradation (thereby, decreasing tryptophan concentration and increasing tryptophan metabolite concentration), for example, by increasing IDO concentration or IDO activity, can suppress T cells. One can manipulate local tryptophan concentrations, and/or modulate the activity of the high affinity tryptophan transporter, and/or administer tryptophan degrading enzymes. Regulation can be further manipulated using cytokines such as MCSF, IFNγ, alone or in combination with antigen or other cytokines.

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29-11-2012 дата публикации

Use of meganucleases for inducing homologous recombination ex vivo and in toto in vertebrate somatic tissues and application thereof

Номер: US20120304321A1
Принадлежит: CELLECTIS SA

A monomer of an I-CreI meganuclease variant wherein said monomer when in dimeric form binds and cleaves DNA.

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13-12-2012 дата публикации

Tumor suppressor designated ts10q23.3

Номер: US20120315631A1

A specific region of chromosome 10 (10q23.3) has been implicated by series of studies to contain a tumor suppressor gene involved in gliomas, as well as a number of other human cancers. One gene within this region was identified, and the corresponding coding region of the gene represents a novel 47 kD protein. A domain of this product has an exact match to the conserved catalytic domain of protein tyrosine phosphatases, indicating a possible functional role in phosphorylation events. Sequence analyses demonstrated the a number of exons of the gene were deleted in tumor cell lines used to define the 10q23.3 region, leading to the classification of this gene as a tumor suppressor. Further analyses have demonstrated the presence of a number of mutations in the gene in both glioma and prostate carcinoma cells. Methods for diagnosing and treating cancers related to this tumor suppressor, designated as TS10q23.3, also are disclosed.

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20-12-2012 дата публикации

Adam6 Mice

Номер: US20120322108A1
Принадлежит: Regeneron Pharmaceuticals Inc

Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

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27-12-2012 дата публикации

Methods and compositions for modulating the activity of the interleukin-35 receptor complex

Номер: US20120328637A1
Принадлежит: St Jude Childrens Research Hospital

The receptor for Interleukin 35 (IL-35) is provided. The Interleukin 35 Receptor (IL-35R) comprises a heterodimeric complex of the Interluekin12Rβ2 receptor and the gp130 receptor. Various compositions comprising the IL-35R complex, along with polynucleotides encoding the same and kits and methods for the detection of the same the same are provided. Methods of modulating the activity of IL-35R or modulating effector T cell functions are also provided. Such methods employ various IL-35R antagonists and agonists that modulate the activity of the IL-35R complex and, in some embodiments, modulate effector T cell function. Further provided are methods for screening for IL-35R binding agents and for IL-35R modulating agents. Various methods of treatment are further provided.

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27-12-2012 дата публикации

Transgenic non-human animals

Номер: US20120331575A1

The invention provides a non-human transgenic animal comprising a transgene encoding angiogenin and food products comprising or obtained from the non-human transgenic animal and uses thereof.

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27-12-2012 дата публикации

Pathogen Restriction Factors

Номер: US20120331576A1

The use of interferon induced transmembrane protein 1, 2, or 3 (IFITM1, 2, or 3) as a viral restriction factor, and methods of using the same to produce virus, transgenic animals expressing exogenous IFITM1, 2, or 3, and methods of treating or inhibiting viral infections by targeting a gene identified herein

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24-01-2013 дата публикации

Genetically modified mice and engraftment

Номер: US20130022996A1

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mII2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/II2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

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24-01-2013 дата публикации

Methods of Modulating Thrombocytopenia and Modified Transgenic Pigs

Номер: US20130024961A1
Принадлежит: Individual

The application provides methods of modulating platelet uptake by liver sinusoidal endothelial cells and of modulating thrombocytopenia. Transgenic pigs modified to bind fewer platelets are provided.

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14-02-2013 дата публикации

Treatment of Pompe's Disease

Номер: US20130039901A1
Принадлежит: Genzyme Therapeutic Products LP

The invention provides methods of treating Pompe's disease using human acid alpha glucosidase. A preferred treatment regime comprises administering greater than 10 mg/kg body weight per week to a patient.

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14-02-2013 дата публикации

Elimination of N-Glycolylneuraminic Acid From Animal Products For Human Use

Номер: US20130039991A1
Принадлежит: UNIVERSITY OF CALIFORNIA

The application is in the field of transgenic (non-human) organisms, sialic acid chemistry, metabolism and antigenicity. More particularly, the invention is related to a method to produce Neu5Gc-free animals and products therefrom comprising disrupting the CMAH gene and thereby reducing or eliminating Neu5Gc from biological material of non-humans.

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07-03-2013 дата публикации

In vivo gene regulation by the combination of knock-in-teto sequence into the genome and tetracycline-controlled trans-suppressor (tts) protein

Номер: US20130061343A1
Автор: Kenji Tanaka, Rene Hen
Принадлежит: Columbia University of New York

Disclosed is a FAST (Flexible Accelerated STOP TetO-knockin) system, an efficient method for manipulating gene expression in vivo to rapidly screen animal models of disease. This invention further discloses a single gene targeting event yielding 2 distinct knockin mice—STOP-tetO and tetO knockin—which permit generation of multiple strains with variable expression patterns: 1) knockout, 2) Cre-mediated rescue; 3) tTA-mediated misexpression; 4) tTA-mediated overexpression; and 5) tTS-mediated conditional knockout/knockdown. Using the FAST system, multiple gain- and loss-of-function strains can therefore be generated on a timescale not previously achievable. These strains can then be screened for clinically-relevant abnormalities. The flexibility and broad applicability of the FAST system is demonstrated by targeting several genes encoding proteins implicated in neuropsychiatric disorders: Mlc1, Neuroligin 3, the serotonin 1A receptor, and the serotonin 1B receptor.

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14-03-2013 дата публикации

Modulating production traits in avians

Номер: US20130067606A1
Принадлежит: Australian Poultry CRC Pty Ltd

The present invention relates to methods of modulating traits, particularly production traits, in avians such as chickens. In particular, the invention relates to the in ovo delivery of a dsRNA molecule, especially siRNAs, to modify production traits in commercially important birds.

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11-04-2013 дата публикации

Artery- and vein-specific proteins and uses therefor

Номер: US20130091591A1

Arterial and venous endothelial cells are molecularly distinct from the earliest stages of angiogenesis. This distinction is revealed by expression on arterial cells of a transmembrane ligand, called EphrinB2 whose receptor EphB4 is expressed on venous cells. Targeted disruption of the EphrinB2 gene prevents the remodeling of veins from a capillary plexus into properly branched structures. Moreover, it also disrupts the remodeling of arteries, suggesting that reciprocal interactions between pre-specified arterial and venous endothelial cells are necessary for angiogenesis. This distinction can be used to advantage in methods to alter angiogenesis, methods to assess the effect of drugs on artery cells and vein cells, and methods to identify and isolate artery cells and vein cells, for example.

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25-04-2013 дата публикации

Tiki1 and Tiki2, Wnt Inhibitors

Номер: US20130101582A1
Принадлежит: Childrens Medical Center Corp

This invention relates to Tiki1 and Tiki2 proteins and nucleic acids, cells expressing the same, and methods for identifying compounds that modulate Tiki1/2 activity for use in the treatment of osteoporosis or cellular proliferative disorders.

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02-05-2013 дата публикации

Genetically Modified Major Histocompatibility Complex Mice

Номер: US20130111617A1
Принадлежит: Regeneron Pharmaceuticals Inc

The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I polypeptide and/or human or humanized β2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

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23-05-2013 дата публикации

GDE Compositions and Methods

Номер: US20130131144A1
Принадлежит: JOHNS HOPKINS UNIVERSITY

The present invention relates to compositions to treat glycerophosphodiester phosphodiesterase (GDE) related disorders. The invention also relates to methods treating GDE related disorders. The invention further relates to kits for treating GDE related disorders in a subject. The invention further relates to methods of identifying novel treatments for treating GDE related disorders in a subject.

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06-06-2013 дата публикации

Zcytor17 heterodimeric cytokine receptor polynucleotides

Номер: US20130143265A1
Принадлежит: Zymogenetics Inc

Novel polypeptide combinations, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed for zcytor17-containing multimeric or heterodimer cytokine receptors that may be used as novel cytokine antagonists, and within methods for detecting ligands that stimulate the proliferation and/or development of hematopoietic, lymphoid and myeloid cells in vitro and in vivo. The present invention also includes methods for producing the multimeric or heterodimeric cytokine receptor, uses therefor and antibodies thereto.

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06-06-2013 дата публикации

Therapeutic compositions

Номер: US20130144048A1
Принадлежит: Alnylam Pharmaceuticals Inc

This application relates to therapeutic siRNA agents and methods of making and using the agents.

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13-06-2013 дата публикации

Novel regulatory proteins and inhibitors

Номер: US20130149309A1

The invention provides a previously uncharacterized protein (gamma secretase activating protein or gSAP) that activates γ-secretase to produce β-amyloid protein (Aβ). Deposition of Aβ has been associated with Alzheimer's disease and other pathologies. The invention thus additionally provides, e.g., screening methods and novel research tools, inhibitors of this novel protein, and methods of diagnosis, treatment and control of Alzheimer's disease and other neurodegenerative conditions associated with deposition of Aβ.

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20-06-2013 дата публикации

Methods and Compositions for the Diagnosis of Cancer Susceptibilities and Defective DNA Repair Mechanisms and Treatment Thereof

Номер: US20130157294A1

Methods and compositions for the diagnosis of cancer susceptibilities, defective DNA repair mechanisms and treatments thereof are provided. Among sequences provided here, the FANCD2 gene has been identified, and probes and primers are provided for screening patients in genetic-based tests and for diagnosing Fanconi Anemia and cancer. The FANCD2 gene can be targeted in vivo for preparing experimental mouse models for use in screening new therapeutic agents for treating conditions involving defective DNA repair. The FANCD2 polypeptide has been sequenced and has been shown to exist in two isoforms identified as FANCD2-S and the monoubiquinated FANCD-L form. Antibodies including polyclonal and monoclonal antibodies have been prepared that distinguish the two isoforms and have been used in diagnostic tests to determine whether a subject has an intact Fanconi Anemia/BRCA pathway.

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18-07-2013 дата публикации

Light-Activated Cation Channel and Uses Thereof

Номер: US20130184817A1
Принадлежит: Leland Stanford Junior University

The present invention provides compositions and methods for light-activated cation channel proteins and their uses within cell membranes and subcellular regions. The invention provides for proteins, nucleic acids, vectors and methods for genetically targeted expression of light-activated cation channels to specific cells or defined cell populations. In particular the invention provides millisecond-timescale temporal control of cation channels using moderate light intensities in cells, cell lines, transgenic animals, and humans. The invention provides for optically generating electrical spikes in nerve cells and other excitable cells useful for driving neuronal networks, drug screening, and therapy.

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08-08-2013 дата публикации

Use of meganucleases for inducing homologous recombination ex vivo and in toto in vertebrate somatic tissues and application thereof

Номер: US20130203840A1
Принадлежит: CELLECTIS SA

A single chain homing endonuclease, comprising a first variant of I-CreI having the amino acid sequence of accession number pdb 1g9y and a second variant of I-CreI variant having the amino acid sequence of accession number pdb 1g9y in a single polypeptide.

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15-08-2013 дата публикации

Transgenic animals with customizable traits

Номер: US20130212723A1
Автор: James West
Принадлежит: MICE WITH HORNS LLC

Disclosed are materials and methods for creating customizable traits in animals. In the demonstration of the principle of the subject invention, a keratin-14 specific promoter is used with red fluorescent protein in the loxp cassette, dominant black (ΔG23) beta defensin 103 in the pigment cassette, and an SV40 (with intron) polyadenylation sequence. When Cre recombinase (or HTNCre) is applied to the animal's skin in a carrier base (e.g., lipid bilayers), fur is permanently genetically modified to turn black in the shape in which the HTNCre was applied.

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22-08-2013 дата публикации

Humanized transgenic mouse model

Номер: US20130217043A1
Принадлежит: Individual

Provided is a transgenic animal model for testing immunogenicity and protective efficacy of human vaccines and the method for generating such a multitransgenic animal. Also disclosed are methods for screening compositions for human vaccine development. More specifically, a mouse model capable of expressing human leukocyte antigen DR4, and human costimulatory molecules (CD80) upon infusion of human HLA-matched hematopoietic stem cells, which can develop into a functional man immune system is provided.

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22-08-2013 дата публикации

Transgenic animals and methods of use

Номер: US20130219535A1
Принадлежит: Trianni Inc

The present invention comprises non-human vertebrate cells and non-human mammals having a genome comprising an introduced partially human immunoglobulin region, said introduced region comprising human V H coding sequences and non-coding V H sequences based on the endogenous genome of the non-human mammal.

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12-09-2013 дата публикации

Lmcd1 cancer markers and methods for their use

Номер: US20130239239A1
Автор: C-Y Chang, Y-S Jou
Принадлежит: Academia Sinica

The present invention provides LMCD1 cancer markers, and methods, compositions, and kits for their use. The invention also provides expression vectors, host cells, and transgenic animals comprising one or more LMCD1 mutations, and methods for their use in characterizing, diagnosing, and treating cancers, and for identifying potential therapeutics. The invention also provides cancer therapeutics.

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19-09-2013 дата публикации

Polynucleotide for use in treatment of influenza a virus induced diseases, encoding modified mx protein, said modified mx protein, and a transgenic animal expressing gene encoding modified mx protein

Номер: US20130245100A1
Принадлежит: Universite de Liege ULG

A method can be used for treating or reducing likelihood of an influenza A virus-induced disease in a mammal. The method includes administering a polynucleotide to the mammal. Theis polynucleotide includes a gene encoding Mx protein having a TRAF2 and/or a TRAF6 binding domain. The TRAF2 and/or TRAF6 binding domain can be represented by the sequences P-X-Q/E-E, P-X-Q/E-X-X-D, or P-X-E-E-X-E. The TRAF2 and/or TRAF6 binding domain can also be located in the Mx protein in a position which corresponds to the position of the hexapeptide PEEESE in the bovine Mx1 protein or in a position which is up to 20 amino acid residues upstream or downstream of that position.

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19-09-2013 дата публикации

Non-Human Animals Expressing pH-Sensitive Immunoglobulin Sequences

Номер: US20130247236A1
Принадлежит: Regeneron Pharmaceuticals Inc

Genetically modified non-human animals are provided that express an immunoglobulin variable domain that comprises at least one histidine, wherein the at least one histidine is encoded by a substitution of a non-histidine codon in the germline of the animal with a hisidine codon, or the insertion of a histidine codon in a germline immunoglobulin nucleic acid sequence. Immunoglobulin genes comprising histidines in one or more CDRs, in an N-terminal region, and or in a loop 4 region are also provided. Immunoglobulin variable domains comprising one or more histidines (e.g., histidine clusters) substituted for non-antigen-binding non-histidine residues. Non-human animals that are progeny of animals comprising modified heavy chain variable loci (V, D, J segments), modified light chain variable loci (V, J segments), and rearranged germline light chain genes (VJ sequences) are also provided. Non-human animals that make immunoglobulin domains that bind antigens in a pH-sensitive manner are provided.

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10-10-2013 дата публикации

Albumin Fusion Proteins

Номер: US20130266553A1

The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

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17-10-2013 дата публикации

Production of Transgenic Avians Using Improved Retroviral Vectors

Номер: US20130276153A1
Принадлежит: Alex J. Harvey, Jeffrey C. Rapp

A transgenic avian containing in its genome an exogenous nucleotide sequence which includes a promoter component and a vector with reduced promoter interference wherein the exogenous nucleotide sequence is integrated into the genome and the avian.

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07-11-2013 дата публикации

Nucleic acid construct for expression of oxidative stress indicator and use thereof

Номер: US20130298263A1

The present invention provides a nucleic acid construct for expressing an oxidative stress indicator comprising: a nucleic acid sequence encoding an Nrf2 protein-derived partial protein that comprises at least an Neh2 domain sequence and substantially lacks or is functionally deficient in an Neh1 domain sequence or an Neh1-Neh3 domain sequence; a stress-inducible promoter sequence positioned upstream of the nucleic acid sequence encoding an Nrf2 protein-derived partial protein; and a nucleic acid sequence encoding a protein capable of generating a detectable signal, the nucleic acid sequence being positioned downstream of the nucleic acid sequence encoding an Nrf2 protein-derived partial protein. The present invention also provides a method for measuring oxidative stress and a method for screening for an anti-oxidative stress agent, using the nucleic acid construct.

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07-11-2013 дата публикации

Biological control

Номер: US20130298266A1
Автор: Dean Thomas, Luke Alphey
Принадлежит: Oxford University Innovation Ltd

The invention relates to a non-human multicellular organism carrying a dominant lethal genetic system, the lethal effect of which is conditional, wherein the lethal effect of the lethal system occurs in the natural environment of the organism.

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07-11-2013 дата публикации

Compositions and methods relating to non-human animals modified to promote production of selected gametes

Номер: US20130298269A1
Принадлежит: Jackson Laboratory

Methods and compositions for producing selected non-human mammalian germ cells and gametes and for making non-human animals using the produced germ cells and gametes are provided by the present invention. Methods of generating a non-human embryo and/or animal derived from donor stem cells, methods of generating chimeric non-human animals having substantially all gametes and/or germ cells derived from the donor stem cells, methods of producing a non-human host embryo lacking functional endogenous germ cells and non-human host embryos incapable of developing endogenous gametes of the present invention are described herein.

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21-11-2013 дата публикации

Promoter-regulated differentiation-dependent self-deleting cassette

Номер: US20130312128A1
Принадлежит: Regeneron Pharmaceuticals Inc

Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3′-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.

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28-11-2013 дата публикации

Novel Inflammation to vivo model

Номер: US20130318641A1
Принадлежит: Hoffmann La Roche Inc

The present invention relates to a non-human animal deficient in the N-terminal domain of the IL-33 gene. Also provided herein is the use of said non-human animal as an in vivo model of inflammatory diseases, especially with regard to screening methods for anti-inflammatory compounds, and methods for evaluating and optimising the pharmacological properties of a given anti-inflammatory compound.

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05-12-2013 дата публикации

Restricted immunoglobulin heavy chain mice

Номер: US20130323791A1
Принадлежит: Regeneron Pharmaceuticals Inc

Mice having a restricted immunoglobulin heavy chain locus are provided, wherein the locus is characterized by a single polymorphic human V H gene segment, a plurality of human D H gene segments and a plurality of J H gene segments. Methods for making antibody sequences that bind an antigen (e.g., a viral antigen) are provided, comprising immunizing a mouse with an antigen of interest, wherein the mouse comprises a single human V H gene segment, a plurality of human D H gene segments and a plurality of J H gene segments, at the endogenous immunoglobulin heavy chain locus.

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12-12-2013 дата публикации

Antibody production

Номер: US20130330771A1
Принадлежит: ERASMUS UNIVERSITY MEDICAL CENTER

A transgenic non-human mammal containing a heterologous lambda light chain gene locus, and/or a heterologous kappa light chain gene locus, and/or a heterologous heavy chain gene locus, each of which can re-arrange so that immunoglobulin heavy and light chain genes are formed and expressed in B-cells following antigen challenge.

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12-12-2013 дата публикации

Humanized Non-Human Animals with Restricted Immunoglobulin Heavy Chain Loci

Номер: US20130333057A1
Принадлежит: Regeneron Pharmaceuticals Inc

Mice, embryos, cells, and tissues having a restricted immunoglobulin heavy chain locus and an ectopic sequence encoding one or more ADAM6 proteins are provided. In various embodiments, mice are described that have humanized endogenous immunoglobulin heavy chain loci and are capable of expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof that is functional in a male mouse. Mice, embryos, cells, and tissues having an immunoglobulin heavy chain locus characterized by a single human V H gene segment, a plurality of human D H gene segments and a plurality of human J H gene segments and capable expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof are also provided.

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02-01-2014 дата публикации

Chimeric gene constructs for generation of fluorescent transgenic ornamental fish

Номер: US20140007265A1
Принадлежит: NATIONAL UNIVERSITY OF SINGAPORE

Four zebrafish gene promoters, which are skin specific, muscle specific, skeletal muscle specific and ubiquitously expressed respectively, were isolated and ligated to the 5′ end of the EGFP gene. When the resulting chimeric gene constructs were introduced into zebrafish, the transgenic zebrafish emit green fluorescence under a blue light or ultraviolet light according to the specificity of the promoters used. Thus, new varieties of ornamental fish of different fluorescence patterns, e.g., skin fluorescence, muscle fluorescence, skeletal muscle-specific and/or ubiquitous fluorescence, are developed.

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09-01-2014 дата публикации

Compositions and methods for regulating metabolism

Номер: US20140011737A1
Автор: Volkhard Lindner
Принадлежит: MAINE MEDICAL CENTER

The present invention features compositions and methods for treating and preventing a metabolic syndrome featuring the collagen triple helix repeat containing-1 (Cthrc1) protein.

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06-02-2014 дата публикации

Antitumor vaccination using allogeneic tumor cells expressing alpha (1,3)-galactosyltransferase

Номер: US20140037692A1
Принадлежит: Central Iowa Health System

The invention relates to methods and compositions for causing the selective targeting and killing of tumor cells. Through ex vivo gene therapy protocols tumor cells are engineered to express an α(1,3)galactosyl epitope. The cells are then irradiated or otherwise killed and administered to a patient. The α galactosyl epitope causes opsonization of the tumor cell enhancing uptake of the opsonized tumor cell by antigen presenting cells which results in enhanced tumor specific antigen presentation. The animal's immune system thus is stimulated to produce tumor specific cytotoxic cells and antibodies which will attack and kill tumor cells present in the animal.

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13-02-2014 дата публикации

Anti-endoglin antibodies and knockin mice expressing novel human/mouse chimeric endoglin

Номер: US20140044724A1
Автор: Ben K. Seon, Hirofumi Toi
Принадлежит: Health Research Inc

Provided are compositions and methods that relate to prophylaxis and therapy of angiogenesis associated disease and includes novel knockin mice which express novel human/mouse chimeric endoglin, vectors for use in making such mice, and murine embryonic stem cells comprising the novel human/mouse transgene. Also provided are anti-human endoglin monoclonal antibodies (mAbs) which can be used as antiangiogenic agents for prophylaxis or therapy of human tumor angiogenesis and human angiogenesis-associated diseases having excessive vascularization. The mAbs do not cross react with murine endoglin. Also provides are methods for using the anti-human endoglin mAbs for prophylaxis or therapy of human tumor angiogenesis and for angiogenesis-associated diseases having excessive vascularization.

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06-03-2014 дата публикации

Test systems and methods for identifying and characterising lipid lowering drugs

Номер: US20140065649A1
Принадлежит: SANOFI SA

The present invention relates to methods for the identification and characterization of therapeutic candidates for use in the treatment of a disease or condition associated with elevated LDL-C levels involving a rodent, methods for the testing of the efficacy of an antibody specifically binding to proprotein convertase subtilisin/kexin type 9 (PCSK9) involving a rodent, as well as a rodent and its use in the identification or profiling of compounds for modulation of a disease or condition associated with elevated LDL-C levels.

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27-03-2014 дата публикации

Genetically Modified Mice and Engraftment

Номер: US20140090095A1

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

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03-04-2014 дата публикации

Recombinant or transgenic factor vii composition, each factor vii molecule having two n-glycosylation sites with defined glycan units

Номер: US20140093491A1
Принадлежит: LFB Biotechnologies SAS

The invention is related to a composition of recombinant or transgenic Factor VII, each molecule of Factor VII of the composition exhibiting two N-glycosylation sites, wherein, among all the molecules of FVII of the composition, the rate of Galα1,3G al glycan moieties is comprised between 0 and 4%. The invention is also related to a process for preparing such a composition of FVII.

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03-04-2014 дата публикации

Delivery of biological materials into cellular organelles

Номер: US20140093964A1
Принадлежит: BRIGHAM YOUNG UNIVERSITY

Systems, devices, and methods for delivering a biological material into an organelle of a cell are provided. In one aspect, for example, a method for introducing biological material into an organelle of a cell includes bringing into proximity a lance and a preselected biological material outside of a cell and charging the lance with a polarity and a charge sufficient to electrically associate the preselected biological material with a tip portion of the lance. The method also includes penetrating an outer portion of the cell with the lance and directing and inserting the lance into an organelle, discharging the lance to release at least a portion of the biological material into the organelle, and withdrawing the lance from the cell.

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06-01-2022 дата публикации

SIGLEC TRANSGENIC MICE AND METHODS OF USE THEREOF

Номер: US20220000083A1
Принадлежит: Alector LLC

Provided herein are transgenic non-human animals whose genomes comprise two or more human genes selected from CD33, Siglec-5, Siglec-7, Siglec-9, Siglec-11, Siglec-14, and Siglec-16, to methods of screening candidate agents that bind to and/or modulate the function and/or activity of at least one of the human genes in the transgenic non-human animals, and to methods of screening candidate agents to determine their effect on one or more activities and/or functions associated with expression of at least one of the human genes in the transgenic non-human animals. Further provided herein are methods of recapitulating a human Siglec immune system in a non-human animal, and methods of generating a non-human animal disease model comprising a human Siglec repertoire. 147.-. (canceled)48. A method of screening candidate agents , the method comprisingi) administering one or more candidate agents to a transgenic non-human animal, wherein the genome of the transgenic non-human animal comprises two or more human genes, wherein the two or more human genes are selected from the group consisting of CD33, Siglec-5, Siglec-7, Siglec-9, Siglec-11, Siglec-14, and Siglec-16, wherein the two or more human genes are expressed in one or more cells of the transgenic non-human animal, and wherein the one of more cells selected from the group consisting of myeloid cells, natural killer (NK) cells, T cells, microglia, and any combination thereof; andii) determining whether the one or more candidate agents bind to and/or modulates the function and/or activity of at least one of the two or more human genes in the transgenic non-human animal.49. A method of screening candidate agents , the method comprisingi) administering one or more candidate agents to a transgenic non-human animal, wherein the genome of the transgenic non-human animal comprises two or more human genes, wherein the two or more human genes are selected from the group consisting of CD33, Siglec-5, Siglec-7, Siglec-9, Siglec-11, ...

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06-01-2022 дата публикации

Genetically Modified Mice and Engraftment

Номер: US20220000084A1
Принадлежит:

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., or is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia. 117.-. (canceled)18. A method comprising:engrafting a second mouse with human hematopoietic cells isolated from a genetically modified first mouse, wherein the genetically modified first mouse is immunocompromised for a mouse immune system, wherein the genetically modified first mouse comprises an engraftment of human hematopoietic cells and a replacement of each allele of the mouse thrombopoietin (TPO) gene with a human TPO gene at the mouse TPO gene locus, and wherein the second mouse is immunocompromised for a mouse immune system.19. The method of claim 18 , wherein the human hematopoietic cells comprise CD34+ cells.20. The method of claim 18 , wherein the first mouse comprises a replacement of a mouse IL-3 gene with a human IL-3 gene at a mouse IL-3 gene locus claim 18 , and a replacement of a mouse GM-CSF gene with a human GM-CSF gene at a mouse GM-CSF gene locus.21. The method of claim 18 , wherein the first mouse is null for a RAG2 gene claim 18 , and null for a mouse interleukin 2 receptor gamma (IL-2Rg) gene.22. The method of claim 18 , wherein the second mouse comprises a replacement of a mouse IL-3 gene ...

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07-01-2016 дата публикации

HUMAN-DERIVED MUTANTS OF THE dSOD1 GENE IN DROSOPHILA AND METHODS OF MAKING AND USING

Номер: US20160000054A1
Автор: Reenan Robert
Принадлежит: Brown University Research Foundation

Genetic models of amyotrophic lateral sclerosis (ALS) are described, which can be used to identify novel treatments of ALS and therapeutic targets. Methods for making and using human-derived mutants of the dSOD1 gene that model familial ALS are provided. Methods of identifying therapeutic ALS gene targets also are provided. 1Drosophila. A mutant organism comprising a mutant dSOD1 gene , a humanized dSOD1 gene , or a partially humanized dSOD1 gene , wherein the mutant dSOD1 gene comprises at least one human-derived SOD1 mutation , and wherein the mutant dSOD1 gene , the humanized dSOD1 gene , or the partially humanized dSOD1 gene replaces at least one of the copies of the endogenous dSOD1 gene.2Drosophila. The mutant organism of claim 1 , wherein the human-derived SOD1 mutation is A4S claim 1 , A4V claim 1 , G37R claim 1 , H48R claim 1 , H71Y claim 1 , G85R claim 1 , R115G claim 1 , D124G claim 1 , G141E claim 1 , G147R or C6S.3. (canceled)4. The mutant organism of claim 1 , wherein the humanized dSOD1 gene claim 1 , or the partially humanized dSOD1 gene further comprises at least one human-derived SOD1 mutation.5Drosophila. The mutant organism of claim 4 , wherein the human-derived SOD1 mutation is A4S claim 4 , A4V claim 4 , G37R claim 4 , H48R claim 4 , H71Y claim 4 , G85R claim 4 , R115G claim 4 , D124G claim 4 , G141E claim 4 , G147R or C6S.6. (canceled)7. (canceled)8. (canceled)9DrosophilaDrosophilaDrosophila. A method of making a dSOD1 mutant organism claim 4 , a humanized dSOD1 mutant organism claim 4 , or a partially humanized dSOD1 mutant organism comprising the steps of:(a) generating a nucleic acid targeting vector comprising a dSOD1 gene with at least one human-derived SOD1 mutation, a humanized dSOD1 gene, or a partially humanized dSOD1 gene;{'i': 'Drosophila', '(b) transforming a organism with said targeting vector; and'}(c) identifying mutants wherein the dSOD1 gene with at least one human-derived SOD1 mutation, the humanized dSOD1 gene, or the ...

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04-01-2018 дата публикации

HUMANIZED IL-4 AND IL-4Ra ANIMALS

Номер: US20180000056A1
Принадлежит: Regeneron Pharmaceuticals, Inc.

Non-human animals comprising a human or humanized IL-4 and/or IL-4Rα nucleic acid sequence are provided. Non-human animals that comprise a replacement of the endogenous IL-4 gene and/or IL-4Rα gene with a human IL-4 gene and/or IL-4Rα gene in whole or in part, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized IL-4 gene under control of non-human IL-4 regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4-encoding sequence with human IL-4-encoding sequence at an endogenous non-human IL-4 locus. Non-human animals comprising a human or humanized IL-4Rα gene under control of non-human IL-4Rα regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4Rα-encoding sequence with human or humanized IL-4Rα-encoding sequence at an endogenous non-human C IL-4Rα locus. Non-human animals comprising human or humanized IL-4 gene and/or IL-4Rα sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided. 153-. (canceled)54. A triply humanized mouse , comprising (i) a replacement of a genomic DNA of a mouse IL-4Rα gene at an endogenous mouse IL-4Rα locus with a human genomic DNA of a human IL-4Rα gene to form a humanized IL-4Rα gene , wherein the genomic DNA of the mouse IL-4Rα gene comprises the ATG initiation codon of exon 1 through exon 5 of the mouse IL-4Rα gene , and the human genomic DNA of the human IL-4Rα gene comprises the ATG initiation codon of exon 1 through exon 5 of the human IL-4Rα gene , wherein the humanized IL-4Rα gene comprises the ATG initiation codon of exon 1 through exon 5 of the human IL-4Rα gene and exons 6-9 of the mouse IL-4Rα gene , wherein expression of the humanized IL-4Rα gene is under control of the mouse IL-4Rα promoter at the endogenous mouse IL-4Rα locus ,(ii) a replacement of a genomic DNA of a mouse IL-4 gene at an endogenous mouse IL-4 locus with a ...

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07-01-2021 дата публикации

TRANSGENIC MAMMALS AND METHODS OF USE THEREOF

Номер: US20210000087A1
Принадлежит:

Transgenic mammals that express canine-based immunoglobulins are described herein, including transgenic rodents that express canine-based immunoglobulins for the development of canine therapeutic antibodies. 1. A transgenic rodent or rodent cell comprising a genome comprising an engineered partly canine immunoglobulin light chain locus comprising canine immunoglobulin λ light chain variable region gene segments , wherein the engineered immunoglobulin locus is capable of expressing immunoglobulin comprising canine variable domains and wherein the transgenic rodent produces more , or is more likely to produce , immunoglobulin comprising λ light chain than immunoglobulin comprising κ light chain.2. The transgenic rodent according to claim 1 , wherein more λ light chain producing cells than κ light chain producing cells are likely to be isolated from said rodent.3. The transgenic rodent according to claim 1 , wherein the transgenic rodent produces at least about 25% claim 1 , 30% claim 1 , 35% claim 1 , 40% claim 1 , 45% claim 1 , 50% claim 1 , 55% claim 1 , 60% claim 1 , 65% claim 1 , 70% claim 1 , 75% claim 1 , 80% claim 1 , 85% claim 1 , 90% or 95% and up to about 100% immunoglobulin comprising λ light chain.4. The transgenic rodent cell according to claim 1 , wherein the transgenic rodent cell claim 1 , or its progeny claim 1 , has at least about a 25% claim 1 , 30% claim 1 , 35% claim 1 , 40% claim 1 , 45% claim 1 , 50% claim 1 , 55% claim 1 , 60% claim 1 , 65% claim 1 , 70% claim 1 , 75% claim 1 , 80% claim 1 , 85% claim 1 , 90% claim 1 , or 95% and up to about 100% claim 1 , probability of producing immunoglobulin comprising λ light chain.5. The transgenic rodent or rodent cell according to claim 1 , wherein the engineered immunoglobulin locus comprises canine V and J gene segment coding sequences embedded in rodent non-coding regulatory or scaffold sequences of a rodent immunoglobulin λ light chain variable region gene locus.6. The transgenic rodent or rodent ...

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07-01-2021 дата публикации

Transgenic chicken that produces human antibodies

Номер: US20210000088A1
Принадлежит: Crystal Bioscience Inc

A transgenic chicken having a genome comprising a modified immunoglobulin heavy chain (IgH) locus is provided. The locus lacks the entire contiguous endogenous chicken V-D-J region and contains a human VH segment, a human D cluster, a human J segment and a plurality of upstream pseudogenes based on human VH sequences. The modified IgH locus undergoes V(D)J recombination in the chicken and the chicken produces antibodies that have a diversified immunoglobulin heavy chain.

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07-01-2021 дата публикации

ENHANCED IMMUNOGLOBULIN DIVERSITY

Номер: US20210000089A1
Принадлежит:

The invention provides compositions and methods for enhanced production of immunoglobulin diversity. Specifically, the invention provides compositions and methods for making accessible a B cell receptor repertoire that has not been culled by developmental tolerance mechanisms. The invention also provides transgenic animals, cells, and antibodies resulting from these compositions and methods. 1. A genetically modified mouse comprising:{'sub': H', 'H', 'H, '(a) a first immunoglobulin heavy chain allele, comprising V, D and Jgene segments and one or more exons encoding immunoglobulin constant domains, in which a first expression cassette comprising a first splice acceptor and a first stop codon is inserted in antisense orientation with respect to transcriptional direction downstream of the first immunoglobulin heavy chain allele Jgene segments and upstream of the first immunoglobulin heavy chain allele exons encoding constant domains, wherein the first cassette is flanked by site-specific recognition sequences; and'}{'sub': H', 'H', 'H, '(b) a second immunoglobulin heavy chain allele comprising V, D and Jgene segments and one or more exons encoding immunoglobulin constant domains, in which a second expression cassette comprising a second splice acceptor and a second stop codon is inserted in sense orientation with respect to transcriptional direction downstream of the second immunoglobulin heavy chain Jgene segments and upstream of the second immunoglobulin heavy chain allele exons encoding constant domains, wherein the second cassette is flanked by site-specific recognition sequences,'}wherein the first immunoglobulin heavy chain allele is capable of expressing a functional first immunoglobulin heavy chain and the second immunoglobulin heavy chain allele can undergo productive VDJ rearrangement but is deficient in expression of a functional second immunoglobulin heavy chain, wherein expression of the first allele can be inactivated and the deficiency in expression of ...

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07-01-2021 дата публикации

MALE ARTHROPOD KILLING FACTORS AND METHODS OF USE THEREOF

Номер: US20210000092A1
Принадлежит:

The present disclosure relates to genetically modified arthropods, genetically modified bacteria, and methods for controlling and/or reducing arthropod populations. 2. The arthropod of claim 1 , wherein the gene encoding the male arthropod killing factor is from a bacterium claim 1 , a prophage claim 1 , or a phage.3Wolbachia. The arthropod of claim 2 , wherein the gene encoding the male arthropod killing factor is from .4. The arthropod of claim 3 , wherein the male arthropod killing factor is wink (WD0626).5. The arthropod of claim 1 , wherein the male arthropod killing factor comprises the amino acid sequence SEQ ID NO:1 claim 1 , or a variant thereof.6. The arthropod of claim 1 , wherein the reduction in viable male offspring is greater than 10%.7. The arthropod of claim 1 , wherein the arthropod is an insect.8Aedes, CulexAnopheles.. The arthropod of claim 7 , wherein the insect is selected from the genera consisting of and9Aedes albopictus, Aedes aegyptiAedes polynesiensis.. The arthropod of claim 8 , wherein the insect is selected from the group consisting of and10Drosophila suzukii.. The arthropod of claim 7 , wherein the insect is11. A method for controlling a population of target arthropods claim 7 , comprising:providing a gene encoding a male arthropod killing factor, and a promoter operably linked to the gene encoding the male arthropod killing factor;transforming a population of arthropods with the gene encoding the male arthropod killing factor and the promoter operably linked to the gene encoding the male arthropod-killing factor; andreleasing the population of arthropods amongst a population of target arthropods, wherein the release of the arthropods reduces the population of target arthropods.12. The method of claim 11 , wherein the gene encoding the male arthropod killing factor is from a bacterium claim 11 , a prophage claim 11 , or a phage.13Wolbachia.. The method of claim 12 , wherein the gene encoding the male arthropod killing factor is from14. ...

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02-01-2020 дата публикации

EFFICIENT PROTEIN EXPRESSION IN VIVO USING MODIFIED RNA (MOD-RNA)

Номер: US20200000881A1
Принадлежит:

Aspects of the invention described herein relate to synthetic, modified RNAs and their use in vivo to modulate gene expression. Aspects of the invention further relate to the use of these synthetic, modified RNAs in myocytes, cardiomyoctes, and tumors. 1. A method for increasing capillary density in cardiac tissue in a subject by expressing a VEGF-A protein in a cardiac tissue in vivo , the method comprising contacting the cardiac tissue in vivo with a composition comprising a synthetic , modified RNA molecule encoding a VEGF-A polypeptide ,wherein the synthetic, modified RNA molecule comprises at least one or more nucleoside base modification selected from the group consisting of: pseudouracil, 2 (thio)pseudouracil,4 (thio)pseudouraci1,2,4-(dithio)psuedouraci1,5-(alkyl)pseudouracil, 5-(methyl)pseudouracil, 5-(alkyl)-2-(thio)pseudouracil, 5-(methyl)-2-(thio)pseudouracil, 5-(alkyl)-4 (thio)pseudouracil, 5-(methyl)-4 (thio)pseudouracil, 5-(alkyl)-2,4 (dithio)pseudouracil, 5-(methyl)-2,4 (dithio)pseudouracil, 1 substituted pseudouracil, 1 substituted 2(thio)-pseudouracil, 1 substituted 4 (thio)pseudouracil, 1 substituted 2,4-(dithio)pseudouracil, 1 (aminocarbonylethylenyl)-pseudouracil, 1 (aminocarbonylethylenyl)-2(thio)-pseudouracil, 1 (aminocarbonylethylenyl)-4 (thio)pseudouracil, 1 (aminocarbonylethylenyl)-2,4-(dithio)pseudouracil, 1 (aminoalkylaminocarbonylethylenyl)-pseudouracil, 1 (aminoalkylamino-carbonylethylenyl)-2(thio)-pseudouracil, 1 (aminoalkylaminocarbonylethylenyl)-4 (thio)pseudouracil, and 1 (aminoalkylaminocarbonylethylenyl)-2,4-(dithio)pseudouracil,such that introducing said synthetic, modified RNA molecule to a cell in the cardiac tissue in vivo results in increased capillary density in the cardiac tissue, and also results in a reduced innate immune response relative to a cell in the cardiac tissue in vivo contacted with a synthetic RNA molecule encoding the polypeptide not comprising said modification.2. The method according to claim 1 , wherein the ...

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04-01-2018 дата публикации

CIRCOVIRUS SEQUENCES ASSOCIATED WITH PIGLET WEIGHT LOSS DISEASE (PWD)

Номер: US20180000927A1
Принадлежит: Zoetis Services LLC

The genome sequences and the nucleotide sequences coding for the PWD circovirus polypeptides, such as the circovirus structural and non-structural polypeptides, vectors including the sequences, and cells and animals transformed by the vectors are provided. Methods for detecting the nucleic acids or polypeptides, and kits for diagnosing infection by a PWD circovirus, also are provided. Method for selecting compounds capable of modulating the viral infection are further provided. Pharmaceutical, including vaccine, compositions for preventing and/or treating viral infections caused by PWD circovirus and the use of vectors for preventing and/or treating diseases also are provided. 114.-. (canceled)15. A vaccine for protecting a pig against infection by a piglet weight loss disease circovirus comprising: an isolated ORF′2 polypeptide of porcine circovirus Type B (PCVB); and a recombinant expression vector.16. The vaccine of claim 15 , wherein the recombinant expression vector is a baculovirus expression vector.17. The vaccine of claim 15 , further comprising an adjuvant.18. The vaccine of claim 15 , further comprising a pharmaceutically or veterinarily acceptable carrier.19. The vaccine of claim 15 , wherein the ORF′2 polypeptide has at least 90% identity to the sequence of SEQ ID NO:26.20. The vaccine of claim 15 , wherein the ORF′2 polypeptide has at least 95% identity to the sequence of SEQ ID NO:26.21. The vaccine of claim 15 , wherein the ORF′2 polypeptide is encoded by a nucleic acid having at least 90% identity to the sequence of SEQ ID NO:25.22. A method for protecting a pig against infection by a piglet weight loss disease circovirus comprising: administering to the pig the vaccine of .23. The method of claim 22 , wherein the vaccine is administered to a pig 3 weeks of age or older.24. The method of claim 22 , wherein the vaccine is administered as a single dose.25. The method of claim 22 , wherein the vaccine is administered via a route selected from the group ...

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06-01-2022 дата публикации

INHIBITORS OF ALPHA-TUBULIN ACETYLATION FOR THE TREATMENT OF PAIN

Номер: US20220002801A1
Принадлежит:

The present invention pertains to novel analgesics useful for treating mechanical pain. The invention suggests the use of inhibitors of α-tubulin acetylation for inhibition of neurological sensations that are mediated by sensory neurons. The perception of mechanical pain is can be modulated by altering the α-tubulin acetylation, in context of the invention in particular by modulation of the expression and/or activity of the enzyme α-tubulin acetyltransferase (Atat). The invention provides the medical application of α-tubulin acetyltransferase inhibitors as analgesics and a screening method for the identification of compounds useful in the treatment of pain. 115-. (cancelled)16. A method for reducing expression of ATAT1 in a subject experiencing mechanical pain mediated by sensory neurons , the method comprising:administering to the subject an effective amount of a nucleic acid that is capable of reducing expression of ATAT1;wherein the mechanical pain is selected from the group consisting of:inflammatory pain, acute mechanical pain, chronic mechanical pain, mechanical hyperalgesia, mechanical allodynia, visceral pain, and labor pain.17. The method of claim 16 , wherein the acute mechanical pain is due to physical trauma selected from soft tissue damage claim 16 , infection and inflammation.18. The method of claim 16 , wherein the acute mechanical pain is selected from pain due to surgery claim 16 , cuts claim 16 , bruises claim 16 , fractured or broken bones claim 16 , hemorrhoids claim 16 , intestinal gas claim 16 , dyspepsia and dental pain such as toothache claim 16 , denture pain and nerve root pain.19. The method of claim 16 , wherein the chronic mechanical pain is a pain that lasts longer than 1 month or beyond the resolution of an acute tissue injury or is recurring or is associated with tissue injury and/or chronic diseases that are expected to continue or progress.20. The method of claim 16 , wherein the chronic mechanical pain is selected from pain due to ...

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07-01-2016 дата публикации

IMIDAZO[1,2-alpha]PYRAZINE DERIVATIVES

Номер: US20160002703A1
Принадлежит: Promega Corp

The present invention provides, among other things, imidazo[1,2-α]pyrazine derivatives. The derivatives are useful in any method which other coelenterazines have been used. For example, the derivatives may be used in a bioluminogenic method to detect the presence of certain compounds or molecules.

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07-01-2021 дата публикации

IMMUNOGLOBULIN VARIANTS AND USES THEREOF

Номер: US20210002359A1
Принадлежит: Genentech, Inc.

Variant immunoglobulins with one or more amino acid modifications in the Fe region that have increased in vivo half-lives, and methods of using the same are provided. 121-. (canceled)22. A variant IgG comprising a human IgG1 Fc region comprising an amino acid substitution at amino acid 307 with glutamine and an amino acid substitution at 434 with alanine , numbered according to the EU index as in Kabat , wherein the variant IgG has an increased half-life compared to the half-life of an IgG having the wild-type human IgG Fc region.23. The variant IgG of claim 22 , which has a higher binding affinity for FcRn at pH 6.0 than at pH 7.4.24. The variant IgG of claim 22 , which has an equal or higher efficacy than the IgG having the wild-type human IgG Fc region.25. The variant IgG of claim 22 , which is a human or humanized IgG.26. A pharmaceutical composition comprising the variant IgG of and a pharmaceutically acceptable carrier.27. A variant IgG comprising a human IgG1 Fc region comprising an amino acid substitution at amino acid 307 with glutamine and an amino acid substitution at 436 with isoleucine claim 22 , numbered according to the EU index as in Kabat claim 22 , wherein the variant IgG has an increased half-life compared to the half-life of an IgG having the wild-type human IgG Fc region.28. The variant IgG of claim 27 , which has a higher binding affinity for FcRn at pH 6.0 than at pH 7.4.29. The variant IgG of claim 27 , which has an equal or higher efficacy than the IgG having the wild-type human IgG Fc region.30. The variant IgG of claim 27 , which is a human or humanized IgG.31. A pharmaceutical composition comprising the variant IgG of and a pharmaceutically acceptable carrier.32. A variant IgG comprising a human IgG1 Fc region comprising an amino acid substitution at amino acid 307 with glutamine and an amino acid substitution at 434 with serine claim 27 , numbered according to the EU index as in Kabat claim 27 , wherein the variant IgG has an increased ...

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07-01-2021 дата публикации

GENETIC ENGINEERING OF NON-HUMAN ANIMALS FOR THE PRODUCTION OF CHIMERIC ANTIBODIES

Номер: US20210002385A1
Принадлежит:

The invention provides non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing transgenic cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention. 1. (canceled)2. A mouse whose genome comprises a transgene encoding a polypeptide comprising an immunoglobulin light chain variable region , wherein the transgene comprises (1) a plurality of immunoglobulin light chain variable (V) exons encoding feline immunoglobulin light chain variable (V) polypeptides; (2) non-coding sequences between the V exons; (3) a plurality of immunoglobulin light chain joining (J) coding sequences encoding feline immunoglobulin light chain joining (J) polypeptides; and (4) non-coding sequences between the J coding sequences; wherein the non-coding sequences between the V exons and the non-coding sequences between the J coding sequences are derived from mouse immunoglobulin light chain non-coding sequences and wherein the transgene is capable of undergoing gene arrangement and thereby upon expression to produce a polypeptide comprising the immunoglobulin light chain variable region.3. The mouse according to claim 2 , wherein the non-coding sequences between the V exons and the non-coding sequences between the J coding sequences are selected from the group consisting of intronic sequences and cis regulatory sequences.4. The mouse according to claim 3 , wherein the cis regulatory sequences are selected from promoters claim 3 , enhancers claim 3 , recombination signal sequences claim 3 , splice acceptor sequences claim 3 , and splice donor sequences.5. The mouse according to claim 2 , wherein the V exons encode kappa light chain V (Vκ) polypeptides or lambda light chain V (Vλ) polypeptides.6. The mouse according to claim 2 , wherein the V exons encode kappa ...

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04-01-2018 дата публикации

WISE/SOST NUCLEIC ACID SEQUENCES AND AMINO ACID SEQUENCES

Номер: US20180002718A1
Принадлежит:

The present invention relates to nucleic acid sequences and amino acid sequences which influence bone deposition, the Wnt pathway, ocular development, tooth development, and may bind to LRP. The nucleic acid sequence and polypeptides include Wise and Sost as well as a family of molecules which express a cysteine knot polypeptide. Additionally, the present invention relates to various molecular tools derived from the nucleic acids and polypeptides including vectors, transfected host cells, monochronal antibodies, Fab fragments, and methods for impacting the pathways. 1. A method for modulating bone deposition comprising contacting a host cell with an antibody to Sost , wherein the antibody prevents wild-type Sost from binding with a Sost binding partner , wherein the Sost binding partner is an LRP having an amino acid sequence selected from the group consisting of SEQ ID NOS: 68 , 73 , 76 , 79 , 84 , and 86.2. The method according to claim 1 , wherein the antibody is a monoclonal antibody.3. The method according to claim 1 , wherein the Sost binding partner is an LRP having an amino acid sequence selected from the group consisting of SEQ ID NOS: 68 claim 1 , 72 claim 1 , and 84.4. The method according to claim 1 , wherein the Sost binding partner is an LRP having an amino acid sequence according to SEQ ID NO: 68.5. The method according to claim 1 , wherein the Sost binding partner is an LRP having an amino acid sequence according to SEQ ID NO: 72.6. The method according to claim 1 , wherein the Sost binding partner is an LRP having an amino acid sequence according to SEQ ID NO: 84.7. A composition for modulating bone deposition comprising an antibody to Sost claim 1 , wherein the antibody prevents wild-type Sost from binding with a Sost binding partner claim 1 , wherein the Sost binding partner is an LRP having an amino acid sequence selected from the group consisting of SEQ ID NOS: 68 claim 1 , 73 claim 1 , 76 claim 1 , 79 claim 1 , 84 claim 1 , and 86.8. The ...

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07-01-2021 дата публикации

DEVELOPMENT OF SUPERIOR CHIMERISM BY hiPSC ENGINEERING AND EMBRYO AGGREGATION

Номер: US20210002616A1
Принадлежит:

Provided herein are method to increase the efficiency of interspecies chimera generation. 1. A method to increase the efficiency of human:non-human animal chimera generation comprising introducing one or more human stem cells into a non-human embryo , wherein multiple embryos are dissociated and the dissociated aggregate is layered with one or more human cells and cultured prior to transfer into a synchronized gilt , wherein the aggregated embryo and cells results in increased efficiency of chimera generation , further comprising knocking down or out the expression of TP53 and/or overexpression BCL-2 in the one or more human cells.2. The method of claim 1 , wherein BCL-2 is overexpressed.3. The method of claim 1 , wherein TP53 expression is reduced/knocked down.4. The method of claim 1 , wherein BCL-2 is overexpressed and TP53 expression is reduced/knocked down.5. The method of claim 1 , wherein the cells are induced human pluripotent stem cells (hiPSCs).6colicoli. The method of claim 1 , wherein one or both alleles of ETV2 claim 1 , NKX2-5 claim 1 , HandII claim 1 , TBX5 claim 1 , MYF5 claim 1 , MYOD claim 1 , MRF4 claim 1 , IL2Rgy/− claim 1 , RAG2−/− claim 1 , IL2Rg−/−; RAG2−/− claim 1 , IL2Rgy/− claim 1 , RAG2−/− claim 1 , IL2Rg+/− claim 1 , RAG2+/− claim 1 , IL2Rgy/+; RAG2+/− claim 1 , IL2Rg+/−; RAG2+/− claim 1 , DGAT (diglyceride acyltransferase) claim 1 , ABCG2 (ATP-binding cassette sub-family G member 2) claim 1 , ACAN (aggrecan) claim 1 , AMELY (amelogenin claim 1 , y-linked) claim 1 , BLG (progestagen-associated endometrial protein) claim 1 , BMP 1B (FecB) (bone morphogenetic protein receptor claim 1 , type 1B) claim 1 , DAZL (deleted in azoospermia like) claim 1 , Eif4GI (eukaryotic translation initiation factor 4 gamma claim 1 , 1) claim 1 , GDF8 (growth/differentiation factor 8) claim 1 , Horn-poll locus claim 1 , IGF2 (insulin-like growth factor 2) claim 1 , CWC15 (CWC15 spliceosome associated protein) claim 1 , KissR/GRP54 (kisspeptin) claim 1 , OFD1Y ...

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07-01-2021 дата публикации

Crispr/cas9 vector combination and application thereof in gene knockout

Номер: US20210002652A1
Принадлежит: Nanjing Genefriend Biotech Inc

Provided is an SgRNA combination, comprising an SgRNA specifically targeting the GGTA1 gene, an SgRNA specifically targeting the CMAH gene and an SgRNA specifically targeting the β4GalNT2 gene. Also provided is a CRISPR/Cas9 vector combination, comprising a GGTA1-CRISPR/Cas9 vector, a CMAH-CRISPR/Cas9 vector and a β4GalNT2-CRISPR/Cas9 vector. Also provided is an applicaton of the CRISPR/Cas9 vector combination in knocking out the GGTA1 gene, the CMAH gene and the β4GalNT2 gene. The knockout rates of the three genes with the specifically targeted SgRNA sequences are respectively 56%, 63%, and 41%. A three genes knockoutpig can be obtained, wherein the three genes related to immune rejectionare knocked out, and heart valves of said pig can be acquired.

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20-01-2022 дата публикации

FABRY DISEASE GENE THERAPY

Номер: US20220016263A1
Автор: Nathwani Amit, Raj Deepak
Принадлежит:

There is described a nucleic acid molecule comprising a nucleotide sequence encoding for a functional α-galactosidase A protein wherein the nucleotide sequence has at least 85% identity to the sequence of SEQ ID NO. 1. Also described is a vector, host cell or transgenic animal comprising the nucleic acid molecule; and a pharmaceutical composition comprising the nucleic acid molecule or the vector. Further, the use of the nucleic acid molecule in a method of treating Fabry disease is described. 117-. (canceled)18. A method of administering a nucleic acid molecule to a subject , comprising administering to the subject the nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide having α-galactosidase A activity , wherein the nucleotide sequence has at least 91% identity to the nucleotide sequence of SEQ ID NO: 1.191. The method of claim , wherein the subject suffers from Fabry disease.201. The method of claim , wherein the nucleotide sequence has at least 92% identity to the nucleotide sequence of SEQ ID NO: 1.211. The method of claim , wherein the nucleotide sequence has at least 93% identity to the nucleotide sequence of SEQ ID NO: 1.221. The method of claim , wherein the nucleotide sequence has at least 94% identity to the nucleotide sequence of SEQ ID NO: 1.231. The method of claim , wherein the nucleotide sequence has at least 95% identity to the nucleotide sequence of SEQ ID NO: 1.241. The method of claim , wherein the nucleotide sequence has at least 96% identity to the nucleotide sequence of SEQ ID NO: 1.251. The method of claim , wherein the nucleotide sequence has at least 97% identity to the nucleotide sequence of SEQ ID NO: 1.261. The method of claim , wherein the nucleotide sequence has at least 98% identity to the nucleotide sequence of SEQ ID NO: 1.271. The method of claim , wherein the nucleotide sequence has at least 99% identity to the nucleotide sequence of SEQ ID NO: 1.281. The method of claim , wherein the nucleotide sequence ...

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12-01-2017 дата публикации

RECOMBINANT CONSTRUCTS AND TRANSGENIC FLUORESCENT ORNAMENTAL FISH THEREFROM

Номер: US20170006843A1
Принадлежит: YORKTOWN TECHNOLOGIES, LP

The present invention relates to the method and use of reef coral fluorescent proteins in making transgenic red, green and yellow fluorescent zebrafish. Preferably, such fluorescent zebrafish are fertile and used to establish a population of transgenic zebrafish and to provide to the ornamental fish industry for the purpose of marketing. Thus, new varieties of ornamental fish of different fluorescence colors from a novel source are developed. 171.-. (canceled)73. The transgenic fish of claim 72 , wherein the first and second fluorescent proteins are ZsGreen1 claim 72 , ZsYellow1 claim 72 , DsRed2 claim 72 , GFP claim 72 , eGFP claim 72 , YFP claim 72 , eYFP claim 72 , BFP claim 72 , eBFP claim 72 , CFP claim 72 , eCFP claim 72 , FP claim 72 , AmCyan1 claim 72 , DsRed-Express claim 72 , AsRed2 claim 72 , HcRed1 claim 72 , mPlum claim 72 , mCherry claim 72 , tdTomato claim 72 , mStrawberry claim 72 , J-Red claim 72 , DsRed-monomer claim 72 , mOrange claim 72 , mKO claim 72 , MCitrine claim 72 , Venus claim 72 , Ypet claim 72 , EYFP claim 72 , Emerald claim 72 , CyPet claim 72 , mCFPm claim 72 , Cerulean claim 72 , or T-Sapphire.74. The transgenic fish of claim 73 , wherein the first and second fluorescent proteins are ZsGreen1.75. The transgenic fish of claim 73 , wherein the first and second fluorescent proteins are DsRed 2.76. The transgenic fish of claim 72 , wherein said fish β-actin promoter is a carp β-actin promoter.77. The transgenic fish of claim 72 , wherein said fish myosin light chain promoter is a zebrafish fast skeletal myosin light chain promoter.78. The transgenic fluorescent fish of claim 72 , wherein each of said genes comprise at least two polyadenylation signals positioned in tandem.79. The transgenic fluorescent fish of claim 78 , wherein said polyadenylation signals are viral polyadenylation signals.80. The transgenic fluorescent fish of claim 79 , wherein said viral polyadenylation signals are SV40 polyadenylation sequences.81. The transgenic ...

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20-01-2022 дата публикации

Synthesis of High Molecular Weight Proteins Using Inteins

Номер: US20220017917A1
Принадлежит:

This disclosure is directed to split intein protein production systems using transgenic target organisms such as . A vector set for transforming a target organism includes: a first vector having a first donor sequence that encodes (i) a first non-native protein and (ii) at least one split intein domain; a second vector having a second donor sequence that encodes (i) a second non-native protein and (ii) at least one split intein domain. The respective split intein domains encoded by the first and second vectors are configured to associate with one another and ligate the first and second non-native proteins to thereby form a fused protein. 1Bombyx mori. A method of producing transgenic , the method comprising:providing a first vector having a first donor sequence that encodes a first non-native protein and at least one split intein domain;providing a second vector having a second donor sequence that encodes a second non-native protein and at least one split intein domain;{'i': 'Bombyx mori', 'incorporating the first vector into one or more cells; and'}{'i': 'Bombyx mori', 'incorporating the second vector into one or more cells,'}wherein the split intein domains encoded by the first and second vectors are configured to associate with one another and ligate the first and second non-native proteins to thereby form a fused protein.2Bombyx mori.. The method of claim 1 , further comprising providing a gene editing assembly that includes a nuclease configured to target one or more locations within a silk protein gene of the3. The method of claim 2 , wherein the gene editing assembly targets the FibH gene.4. The method of claim 1 , wherein the first donor sequence claim 1 , the second donor sequence claim 1 , or both encode for a spider silk protein.5. The method of claim 4 , wherein the spider silk protein comprises an AS28 protein claim 4 , a MaSp1 protein claim 4 , a MaSp4 protein claim 4 , or combination thereof.6. The method of claim 4 , wherein the spider silk protein ...

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