105 results about "Genetically modified animal" patented technology

The present invention belongs to the technical field of genetic engineering, and particularly relates to the use of an exogenous gene integration site, a homologous recombination vector, and a method for constructing a transgenic pig. The safe site for exogenous gene integration provided by the present invention is the region between the genes LOC100155859 tubulin alpha-1B chain-like and LOC100517052 histone H3.3-like on porcine chromosome 11. The present invention further fully verifies this safe site in transgenic animals and cells. During the passage process, the exogenous gene can be stably and highly expressed, and has no side effects on cells and tissues. Therefore, the safe site provided by the present invention has good application prospects in genetic engineering.

The invention provides a construction method and application of a transgenic animal model with osteoclast specific deletion, and belongs to the technical field of gene engineering. The invention provides a method for constructing an animal model of an osteoclast expression diphtheria toxin receptor, and particularly provides a method for constructing the animal model of the osteoclast expression diphtheria toxin receptor by using a Cre-loxP method. According to the method, the diphtheria toxin receptor is specifically expressed in the osteoclast, and the osteoclast can be specifically deleted by injecting the diphtheria toxin. The animal model of the osteoclast expression diphtheria toxin receptor prepared by the method can stably inherit after being established, is economical and reliable, can provide important theoretical and practical guidance for bone tumor treatment, also provides powerful animal model support for research of bone tumor growth correlation, and has a wide application prospect. Technical conditions are provided for screening, developing, preventing or treating medicines for bone tumors.

Genetically modified animals and cells with humanized light chain immunoglobulin locus and / or humanized heavy chain immunoglobulin locus. The animals and cells can also express a human or chimeric (e.g., humanized) major histocompatibility complex (MHC) protein complex.

Provided is a polynucleotide including a nucleotide sequence encoding a vestigial like 4 protein and a cis-regulatory element that controls hepatocyte-specific expression of the sequence encoding a vestigial like 4 protein. Also provided is a viral vector including the polynucleotide, and a cell or organism transfected by the polynucleotide. Also provided is a method of treating steatohepatitis, obesity, hyperglycemia, diabetes, insulin resistance, liver inflammation, or decreasing white adipose tissue in the subject. Also provided is a method of screening a treatment for fatty liver disease or prevention of cirrhosis, comprising feeding a diet high in fat, fructose, and / or cholesterol to a transgenic animal having an hepatocyte-specific vestigial like protein gene disruption, administering the treatment to the transgenic animal, and detecting a difference in liver morphology or liver function between the transgenic animal and a control animal.

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 present invention relates to processes for the oxidation of sesquiterpenes comprising fused 5- and 7-membered rings using mutant Cytochrome P450 family 102A sub-family member (CYP102A) enzymes. The invention also relates to mutant CYP102A enzymes, polynucleotides encoding the enzymes, cells expressing the enzymes, transgenic animals or plants comprising the enzymes, and compounds produced by the processes.

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.

The invention discloses an application of SB216763 in improving the in-vitro proliferation capacity of porcine spermatogonium. Therefore, the SB216763 can be used as an additive of the porcine spermatogonial cell in-vitro culture medium, and the porcine spermatogonial cell in-vitro culture medium combined with various growth factors is prepared. Researches show that clone groups of the porcine spermatogonium cultured by the culture medium additionally added with the SB216763 are increased, the number of the clone groups is remarkably increased, the expression quantity of genes related to proliferation is remarkably increased, apoptosis genes are remarkably reduced, and the expression of genes related to reproductive specificity and pluripotent maintenance is also increased, so that the in-vitro proliferation and long-term maintenance of the porcine spermatogonium are improved, and the porcine spermatogonium can be used for preparing a novel culture medium for the porcine spermatogonium. Therefore, the in-vitro culture level of the PSCs is systematically improved. Therefore, the invention provides a reliable basis for establishing a long-term, stable and efficient in-vitro culture system of the porcine spermatogonium, and provides a stable and efficient cell model for gene editing of the porcine spermatogonium, preparation of transgenic animals and research on reproductive diseases; the method also has potential application value in the aspects of genetic improvement of pig breeds or preservation of male germplasm resources.

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.

The invention discloses an ultra-stable red fluorescent protein. The fluorescent protein disclosed by the invention is a protein with an amino acid sequence SEQ ID No.4. Experiments prove that the fluorescent protein has excellent electron microscope sample preparation resistance, can retain more fluorescent signals after osmic acid treatment, and can tolerate embedding of Epon resin; meanwhile, the fluorescent protein has excellent thermal stability, and can retain more fluorescent signals at 90 DEG C; in addition, the fluorescent protein has high chemical stability and light stability. Based on the related properties of the fluorescent protein, the fluorescent protein can be used in the fields of protein labeling, various types of fluorescence imaging and super-resolution photoelectric correlated imaging, and is used for tracking the structural and morphological changes of samples such as proteins, subcellular organelles, local cell regions and cells; the kit can be used for packaging related viruses or transgenic animals, marking specific proteins, specific organelles or specific cells, and realizing rapid transparent tissue imaging and expansion super-resolution imaging.

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 application relates to an animal or cell having a myostatin gene in which 12 base pairs of the second exon are deleted. The present application may also comprise a composition capable of manipulating the deletion of 12 base pairs of a myostatin gene to construct the animal or the cell. The present application also relates to use of the composition for increasing muscle.

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.

A human immunoglobulin heavy chain transgene construct encoding a long CDR3 region is provided. The heavy chain transgene comprises a plurality of VH regions longer than an average value, which are operably linked to a plurality of D-D fusion segments. Transgenic animals comprising the transgene are also provided. Methods of using these transgenic animals are also provided.

(i) Rag1 and / or Rag2 gene knockout; (ii) IL2rg gene knockout; and (iii) a homozygous null mutation in the non-human animal heme oxygenase-1 (Hmox-1) gene, and optionally a Fah gene knockout, and / or expressing one or more human or humanized polypeptides, genetically modified cells and genetically modified non-human animals (e.g., rats and mice) are provided herein. Methods and compositions for making and using such genetically modified cells and non-human animals are also provided.

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.

The invention provides a space-time controlled recombinant cccDNA transgenic animal model as well as application and a preparation method thereof.

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.

To provide a donor animal which can provide a pulmonary xenograft having an improved functionality.SOLUTION: The present invention is directed to transgenic animals (e.g., transgenic porcine animals) comprising multiple genetic modifications that advantageously render these animals suitable donors for xenotransplantation. The present invention extends to organs, organ fragments, tissues and cells derived from these animals and their therapeutic use. The present invention further extends to methods of making such animals. In the first aspect, the present invention provides the transgenic porcine animals that include at least four transducing genes that are incorporated and expressed in the single gene locus under the control of at least two promoters and lack expression of alpha-1,3-galactosyltransferase.SELECTED DRAWING: Figure 1

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.