54 results about "Genetically modified animal" patented technology

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.

Human immunoglobulin light chain transgene constructs are provided that encode at least two different rearranged light chain V-J regions arranged in such a manner that only one of the alternate light chains is expressed from the construct upon recombination in B cells. In some embodiments, the transgene comprises two, three or four different rearranged light chain V-J regions. Transgenic animals comprising the transgene are also provided. The light chain transgenes thus allow for expression of two, three or four alternate fixed light chains in the animals. Methods of using the transgenic animals are also provided.

Provided are genetically modified animals and cells with humanized NKC and / or Ly49 locus. In one aspect, the genetically-modified, non-human animal comprises at an endogenous NKC locus, one or more human NKC genes, and / or at an endogenous Ly49 locus, one or more human KIR genes. In some embodiments, the animal comprises an endogenous Clec1b gene. In one aspect, the animal comprises at a safe harbor locus (e.g., an endogenous Hipp11 orRosa26 gene locus), one or more human KIR genes.

The invention discloses application of a LOXL2 gene in resisting avian leukosis virus infection, and belongs to the technical field of biology. The nucleotide sequence of the LOXL2 gene is as shown in SEQ ID NO. 1. The invention provides a new gene target LOXL2 related to avian leukosis virus infection resistance, and proves the effect of the LOXL2 gene in regulating and controlling avian leukosis virus replication. Replication of the avian leukemia virus can be promoted by inhibiting expression of the LOXL2 gene in a host cell, and replication of the avian leukemia virus can be inhibited by overexpressing the LOXL2 gene in the host cell. According to the invention, favorable theoretical guidance and technical support are provided for the application of the LOXL2 gene as a target in the aspects of development of drugs for treating avian leukemia, breeding of transgenic animals for resisting avian leukemia, construction of avian leukemia virus infection models and the like, and the LOXL2 gene has wide application prospects and extremely high market value.

Chimeric transgenic immunoglobulin (Ig) mice are provided that contain a modified heavy chain locus in which the endogenous mouse D and J segments have been deleted and a human heavy chain Ig transgene inserted in their place, thereby expressing an antibody repertoire that utilizes human and mouse VH in the heavy chain linked to human D and JH segments, respectively, increasing antibody diversity. Methods for preparing and using the transgenic animals (e.g., to raise antibodies) are also provided.

The application discloses a Buster transposon system and application thereof, and the system comprises AnBT, CrBT, HvBT, LcBT and LlBT transposons and corresponding transposases, the nucleotide sequences of the AnBT, CrBT, HvBT, LcBT and LlBT transposons are shown in SEQ ID No. 1-5, and the transposases are wild type or enhanced type. The application obtains key elements such as target site repeat (TSD) and terminal inverted repeat (TIR) of the AnBT, CrBT, HvBT, LcBT and LlBT transposons and corresponding transposase sequences through molecular reconstitution, and constructs a set of gene transfer vector systems. The AnBT, CrBT, HvBT, LcBT and LlBT vector systems can effectively mediate gene transfer through cell verification, and have great application potential in transgenic animal preparation and gene therapy.

This disclosure provides, among other things, a transgenic animal that uses gene conversion for antibody diversification, comprising B cells in which the endogenous immunoglobulin heavy chain locus comprises: (a) a functional immunoglobulin heavy chain gene comprising a nucleic acid encoding an autonomous heavy chain (AHC) variable domain; and (b) a plurality of pseudogenes that are operably linked to said functional immunoglobulin heavy chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding the AHC variable domain of (a), wherein the pseudogenes are upstream or downstream of the functional immunoglobulin heavy chain gene.

Provided are human anti-thymocyte globulin (ATG) products, and methods of making and using the same. In particular, the disclosure provides an ungulate-derived polyclonal immunoglobulin, comprising a population of fully human or substantially human immunoglobulins. The population of fully human or substantially human immunoglobulins specifically binds human thymocytes, T cells, B cells, and / or monocytes. Such compositions may be made by immunization of transgenic animals having a human Ig locus with human thymocytes. This method generates polyclonal immunoglobulin with yield, purity, and antigen specificity that enable the use of this product in medical applications.

A human immunoglobulin heavy chain transgene construct is provided that encodes a long CDR3 region. The heavy chain transgene comprises multiple VH regions that are longer than average and operably linked to multiple DD fusion segments. Transgenic animals containing the transgene are also provided. Methods for using the transgenic animals are also provided.

This disclosure provides, among other things, strategies for minimizing antibody diversification in a transgenic animal that uses gene conversion for antibody diversification. In some embodiments, the animal may comprise a genome comprising an endogenous immunoglobulin light chain locus comprising: (a) a functional immunoglobulin light chain gene comprising a nucleic acid encoding a light chain variable region; and (b) a plurality of pseudogenes that are operably linked to the functional immunoglobulin light chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding a light chain variable region, wherein the pseudogenes are upstream or downstream of the functional immunoglobulin light chain gene and encode the same amino acid sequence as the light chain variable region of the functional immunoglobulin light chain gene of (a). In other embodiments, the locus may have a tandem array of coding sequences for the light chain.

Provided is a method for producing an antibody and the antibody produced by the method. The method includes immunizing an animal transplanted with stems cell with differentiation potential using an antigen and obtaining an antigen-specific antibody. The stem cells with differentiation potential are derived from a donor animal carrying one or more human immunoglobulin variable region gene segments. The method solves problems in the prior art including long transportation time and high costs associated with live transgenic animals used for producing human antibodies due to policy and quarantine requirements. When producing antibody against a target antigen having high homology with a transgenic animal, an immunosuppressed animal with a target antigen-encoding gene knockout is used as a transplantation recipient, which solves the problem in the prior art where transgenic animals have difficulty generating antibodies against homologous regions of the target antigen between humans and transgenic animals.

The invention belongs to the field of transgenic animals, and relates to an MET gene modified non-human animal. Specifically, the present invention provides a method of making a genetically modified non-human animal comprising modifying a non-human animal genome such that the modified non-human animal genome comprises a nucleotide sequence encoding a human or chimeric hepatocyte growth factor receptor (MET) protein. Also provided is a genetically modified non-human animal genome comprising a nucleotide sequence encoding a human or chimeric MET protein. The non-human animal obtained by the method provided by the invention provides a powerful tool for researching the function of the MET protein, and provides a platform for screening related drugs.

The application discloses application of a LOXL2 gene in resisting avian leukemia virus infection and belongs to the technical field of biotechnology.The nucleotide sequence of the LOXL2 gene is shown as SEQ ID NO.1.The application provides a new gene target point LOXL2 related to resisting avian leukemia virus infection, and proves the role of the LOXL2 gene in regulating avian leukemia virus replication.Inhibition of LOXL2 gene expression in host cells can promote avian leukemia virus replication, and overexpression of the LOXL2 gene in host cells can inhibit avian leukemia virus replication.The application provides favorable theoretical guidance and technical support for application of the LOXL2 gene as a target point in developing drugs for treating avian leukemia, breeding transgenic animals resisting avian leukemia, and constructing an avian leukemia virus infection model, and has a wide application prospect and extremely high market value.

The present invention addresses the problem of providing: a genetically modified cultured cell or a genetically modified animal each allowing a human sapovirus to proliferate regardless of host characteristics as barriers to proliferation in mammalian cells; and an application of the cell or animal to a screening method. The present inventors have solved the problem by finding that a genetically modified cultured mammalian cell having a human CD36-encoding gene incorporated therein and a mammal having such a cell as a self-cell show acquired susceptibility to human sapovirus infection, and providing, for example, a screening method for a drug relevant to a human sapovirus on the basis of the finding.

This invention discloses a method for constructing an immune animal model for preparing biofusion enzyme antibodies and its application. The method includes the following steps: designing and screening sgRNAs with high cleavage efficiency based on signal protein genes, and constructing an sgRNA-Cas9 expression vector; linearizing the plasmid by double enzyme digestion, and then ligating it with a signal protein gene fragment containing left and right homologous arms to obtain the Donor plasmid; co-transfecting the sgRNA-Cas9 expression vector and the Donor plasmid into target animal somatic cells, and screening to obtain positive somatic cells that stably integrate the target gene; using the positive somatic cells as nuclear donors for nuclear transfer to construct recombinant embryos, and transferring the recombinant embryos into recipient female animals; after delivery, identifying transgenic animal individuals carrying biofusion enzyme antibodies by genomic PCR. Based on this transgenic animal model, different target antibodies with clinical value can be developed.

Chimeric transgenic immunoglobulin (Ig) mice comprising altered heavy chain loci are provided in which endogenous mouse D and J segments have been deleted and at which a human heavy chain Ig transgene is inserted, such that the transgenic Ig mice express an antibody library that utilizes human VH and mouse VH in the heavy chain, each linked to human DH and JH segments, thus, enhanced diversity is produced. Methods of making and using transgenic animals (e.g., to produce antibodies) are also provided.

The present invention relates to regulatable adeno-associated virus (AAV) vectors as well as to their use in gene therapy. It further relates to corresponding nucleic acid molecules, host cells, non-human transgenic animals, pharmaceutical compositions and kits.

The present disclosure relates to transgenic animals with nuclear genomes comprising knockouts of both alleles of an SLA-DQ gene and / or an SLA-DR gene. The disclosure provides transgenic pigs, transplant products from the transgenic pigs and xenotransplantation methods utilizing the transplant products for treatment of transplant rejection, especially in humans.

The present invention provides genetically modified animals (e.g., mice), humanized heavy chain antibodies, humanized nanobodies, and methods for producing and using them. [Solution] Provided are genetically modified non-human animals (e.g., genetically modified mice) that can be designed to produce heavy chain antibodies that can be used to generate single-domain antibodies or nanobodies. In one embodiment, a genetically modified mouse is provided comprising a germline modification comprising deletion of nucleic acid sequences comprising one or more heavy chain C region genes; the genetically modified mouse expresses an IgG heavy chain antibody and secretes an IgG heavy chain antibody in its serum.

The present disclosure relates to transgenic animals with nuclear genomes comprising knockouts of both alleles of an SLA-DQ gene and / or an SLA-DR gene. The disclosure provides transgenic pigs, transplant products from the transgenic pigs and xenotransplantation methods utilizing the transplant products for treatment of transplant rejection, especially in humans.

Provided herein are isolated nucleic acids, vectors, recombinant cells, and transgenic animals capable of expressing at least one or more bluebuck gene variants associated with gray / blue coat color and / or melanogenesis and / or altered facial pattern. Also provided are methods of making recombinant cells and / or transgenic animals that comprise at least one bluebuck (Hippotragus leucophaeus) gene variant associated with gray / blue coat color and / or melanogenesis and / or altered facial pattern.

Provided in the present invention are a genetically modified animal having a restricted humanized light chain immunoglobulin locus, a method for producing the animal, and a method for producing a common light chain antibody and an antibody library thereof using the animal. The restricted humanized light chain immunoglobulin locus comprises a portion of a V region and a portion of a J region from a light chain Kappa variable region locus of a human immunoglobulin.

The invention discloses a construction method and application of a sperm-specific hOdf2-GFP transgenic mouse model, and relates to the technical field of reproductive biology and transgenic animal model construction. According to the construction method disclosed by the invention, based on a piggyBac transposon expression vector system, a DNA (Deoxyribose Nucleic Acid) sequence containing a coding human source Odf2 is effectively connected with a Protamine1 promoter. The transgenic positive mouse constructed by the method can specifically express human Odf2, has a dynamic change from sperm to zygote to eight cell stages, realizes early continuous visual tracking of embryos, has genetic stability, keeps expression and phenotype consistency across generations, and has a good application prospect. The method can be applied to the fields of environmental poison evaluation, asthenospermia mechanisms, drug screening and the like.

The present application relates to the technical field of biological medicine, and particularly discloses a recombinant adeno-associated virus vector, a preparation method thereof, and application of the vector in prevention and treatment of atherothrombosis. The present application provides a new pharmaceutical use of Metrnl protein or gene and a synergistic agent thereof, and is used for preparing a drug for preventing and treating atherothrombosis. A multi-level Metrnl gene delivery system and a transgenic animal model are constructed, including a naked plasmid, a lipid nanoparticle (LNP) and an AAV9 vector, and an ApoE ‑ / ‑ ; Metrnl-OE mouse model is established. Experiments show that naked plasmid and LNP delivery have no obvious effect on atherothrombosis, while AAV9 delivery can significantly reduce the incidence of atherothrombosis, and AAV9-CMV-Metrnl is superior to AAV9-ICAM2-Metrnl; at the same time, a continuous high-expression model and a recombinant protein both show better protective effects. The present application screens a high-efficiency gene delivery system, and provides a new technical solution for prevention and treatment of atherothrombosis.

The present invention provides a non-human animal having a novel fiber and a method for preparing the non-human animal. Specifically, the present invention provides a non-human animal with reduced expression or functions of at least one gene constituting the Krt or KAP family, and a method for preparing the non-human animal.

A composition for modifying a myostatin gene, the composition comprising: a guide RNA; a Cas protein; wherein the target sequence is one selected from: SEQ ID NO: 38-60 and the guide sequence is one s

The invention discloses a transgenic animal antibody high-yield expression system based on double-copy site-specific integration and application of the transgenic animal antibody high-yield expression system. According to the invention, dual-copy anti-staphylococcus aureus enterotoxin B (SEB) monoclonal antibody genes are integrated at safe sites of mouse ROSA26 and H11 in a targeting manner, so that the whole-body high-level stable expression of the antibody in a mouse body is realized, and the yield and neutralizing activity of the antitoxin antibody are remarkably improved. The invention provides a new thought and a new strategy for the development of a low-cost and high-efficiency therapeutic antibody bioreactor. Besides, the constructed SEB antibody gene animal model provides an important tool for research on staphylococcus aureus infection resistance, provides a potential model animal solution for disease prevention and control of animal husbandry, and has good application value and industrial transformation prospect.

Provided are human anti-thymocyte globulin (ATG) products, and methods of making and using the same. In particular, the disclosure provides an ungulate-derived polyclonal immunoglobulin, comprising a population of fully human or substantially human immunoglobulins. The population of fully human or substantially human immunoglobulins specifically binds human thymocytes, T cells, B cells, and / or monocytes. Such compositions may be made by immunization of transgenic animals having a human Ig locus with human thymocytes. This method generates polyclonal immunoglobulin with yield, purity, and antigen specificity that enable the use of this product in medical applications.

Provided herein are isolated nucleic acids, vectors, recombinant cells, and transgenic animals capable of expressing at least one or more bluebuck gene variants associated with gray / blue coat color and / or melanogenesis and / or altered facial pattern. Also provided are methods of making recombinant cells and / or transgenic animals that comprise at least one bluebuck (Hippotragus leucophaeus) gene variant associated with gray / blue coat color and / or melanogenesis and / or altered facial pattern.

The application belongs to the technical field of biology, and particularly relates to a transgenic animal model and a construction method and application thereof. flox / flox The transgenic mouse is mated with the Agc1-CreER transgenic mouse to generate the Axin1 Agc1ER Conditional knockout mouse, and then Axin1 Agc1ER The conditional knockout mouse Axin1 expression is down-regulated, and a disease combined model with pathological characteristics of growth plate chondrocyte hypertrophy, ectopic ossification and knee joint articular cartilage degeneration is successfully established; the Axin1 Agc1ER Conditional knockout mouse animal model has growth plate chondrocyte hypertrophy, ectopic ossification and osteoarthritis characteristics similar to the related pathological characteristics in clinic, and can be used for systematically researching the pathogenesis of growth plate chondrocyte hypertrophy, ectopic ossification and osteoarthritis and further screening drugs for treating related diseases.