Abstract: A promoter activation sequence that allows for stable and efficient expression of a DNA of interest in a mammalian cell is provided. The promoter activation sequence has a nucleotide sequence represented by SEQ ID NO: 1, or a nucleotide sequence of 850 or more in a nucleotide sequence having 85% or higher sequence identity thereto. Also disclosed are an expression vector having the promoter activation sequence, a promoter, and a DNA of interest, a mammalian cell and a mammal including the expression vector.

Abstract: Provided is a method for producing a human artificial chromosome vector with high safety by using a human cell. The method for producing a human cell comprising a human artificial chromosome vector comprises: substantially eliminating endogenous genes of long-arm and short-arm in a disomic human cell containing a pair of the homologous human chromosomes or a trisomic human cell containing trisomy of the homologous human chromosomes, from one of two chromosomes of the disomy or one or two of three chromosomes of the trisomy, thereby producing a cell population containing a human cell containing a human artificial chromosome vector comprising long-arm moiety and short-arm moiety substantially containing no endogenous gene, a human centromere, and a telomere; and collecting the human cell containing the human artificial chromosome vector from the cell population. As well as, the human cell comprises the human artificial chromosome vector.

Abstract: Provided is an approach for achieving the expansion of a human antibody repertoire in a human antibody-producing non-human animal. Provided is a mammalian artificial chromosome vector comprising a human immunoglobulin heavy chain locus in which a D-region of a human immunoglobulin heavy chain is modified, and a human immunoglobulin light chain locus, a mammalian cell or a non-human animal comprising this mammalian artificial chromosome vector, and a method for substituting a D-region of a human immunoglobulin heavy chain with a modified sequence thereof in the production of this artificial chromosome vector.

Abstract: Provided is a human antibody against a spike protein of coronavirus, in particular, against a protein in an extracellular region or a receptor-binding domain.

Abstract: This application provides: a non-human animal that comprises a mouse artificial chromosome comprising a human antibody heavy chain gene or gene locus, a human antibody light chain ? gene or gene locus, and/or a human antibody light chain ? gene or gene locus, and in which endogenous antibody genes or gene loci corresponding to at least 2 human antibody genes or gene loci have been knocked out, wherein the animal can be stably retained through generations and can produce human antibodies; a method for producing the non-human animal; and a method for producing human antibodies using the non-human animal.

Abstract: An object of the present invention is to provide a method for producing a reversibly immortalized cell which can allow a cell into which an immortalizing gene is introduced to proliferate over a long period without damaging the chromosome of the cell, and is capable of removing the immortalizing gene, and to provide a method for obtaining a large amount of a reversibly immortalized cell that can be cloned and has stable quality. The present invention provides a method for producing a reversibly immortalized cell, comprising the steps of: introducing a chromosomally non-integrated RNA virus vector loaded with one or two or more immortalizing gene(s), selected from the group consisting of Bmi-1 gene, TERT gene, and SV40T gene, into a mammalian cell so that the immortalizing gene is expressed in the cell; and culturing the obtained cell for proliferation.

Abstract: In this application, the provided are: a Down syndrome rat model characterized in that a rat gene homologous to at least one gene present on a human chromosome 21 or fragment thereof is a trisomy and is transmittable to progeny; or a Down syndrome rat model characterized in that it comprises a human chromosome 21 or fragment thereof, or an exogenous rat chromosome or fragment thereof on which a rat gene homologous to the human chromosome 21 or fragment thereof is present, wherein at least one gene on the human chromosome 21 or fragment thereof or on the exogenous rat chromosome or fragment thereof is added to endogenous rat genes homologous to the at least gene so as to become a trisomy and to be transmittable to progeny: and a method for producing the Down syndrome rat model.

Abstract: This application provides a method for preparing human cell-derived microcells from human cells comprising DNA of interest, comprising: a step of culturing human cells in a medium containing at least one micronucleus inducer selected from the group consisting of microtubule polymerization inhibitors (excepting colcemid), microtubule depolymerization inhibitors, and spindle checkpoint inhibitors, thereby to produce human cell-derived microcells; and a step of collecting human cell-derived microcells comprising the DNA of interest, and a method for preparing human cells comprising DNA of interest by use of the method, which can be also applied to non-human animal cells.

Abstract: The present application provides: a method for producing human induced pluripotent stem (iPS) cells comprising an exogenous chromosome having a DNA of interest using the MMCT method; and a method for expressing the exogenous gene in the human iPS cells prepared by the method for producing human iPS cells, or in undifferentiated or differentiated cells derived from the human iPS cells induced to differentiate from the human iPS cells.

Abstract: A mouse artificial chromosome vector is stable in rodent cells, tissues, and/or individuals, specifically a mouse artificial chromosome vector derived from a mouse chromosome selected from mouse chromosome 10 and mouse chromosome 16. A cell or a non-human animal may include the vector. The vector may be used for producing proteins and human antibodies.

Abstract: This application provides: a nucleic acid construct characterized by comprising, in a mammalian artificial chromosome vector, a DNA sequence of interest, a matrix attachment region, and a replication origin, and by using for high expression of the DNA; a mammalian cell comprising the nucleic acid construct; and a method for high production of a protein encoded by the DNA of interest in the mammalian cell.

Abstract: In this application, the provided are: a Down syndrome rat model characterized in that a rat gene homologous to at least one gene present on a human chromosome 21 or fragment thereof is a trisomy and is transmittable to progeny; or a Down syndrome rat model characterized in that it comprises a human chromosome 21 or fragment thereof, or an exogenous rat chromosome or fragment thereof on which a rat gene homologous to the human chromosome 21 or fragment thereof is present, wherein at least one gene on the human chromosome 21 or fragment thereof or on the exogenous rat chromosome or fragment thereof is added to endogenous rat genes homologous to the at least gene so as to become a trisomy and to be transmittable to progeny: and a method for producing the Down syndrome rat model.

Abstract: This application provides: a non-human animal that comprises a mouse artificial chromosome comprising a human antibody heavy chain gene or gene locus, a human antibody light chain ? gene or gene locus, and/or a human antibody light chain ? gene or gene locus, and in which endogenous antibody genes or gene loci corresponding to at least 2 human antibody genes or gene loci have been knocked out, wherein the animal can be stably retained through generations and can produce human antibodies; a method for producing the non-human animal; and a method for producing human antibodies using the non-human animal.

Abstract: Disclosed is a mouse artificial chromosome vector, comprising: a natural centromere derived from a mouse chromosome; a mouse-chromosome-derived long-arm fragment formed by deleting a long-arm distal region at a mouse chromosome long-arm site proximal to the centromere; and a telomere sequence, wherein the vector is stably retained in a cell and/or tissue of a mammal. In addition, disclosed are cells or non-human animals comprising the vector, and use of the cells or non-human animals.

Abstract: A chimeric non-human animal having an in vivo human hepatocyte population, wherein the effects of non-human animal cells on drug metabolism are suppressed or deleted is provided. A method for producing a chimeric non-human animal that lacks a drug-metabolizing system or has a suppressed drug-metabolizing system and is provided with a drug-metabolizing system driven by human hepatocytes, is provided. The method comprises transplanting human hepatocytes into a non-human animal characterized by (i) being immunodeficient, (ii) having liver damage, and (iii) lacking the functions of an endogenous Cyp3a gene.

Abstract: Disclosed is a mouse artificial chromosome vector, comprising: a natural centromere derived from a mouse chromosome; a mouse-chromosome-derived long-arm fragment formed by deleting a long-arm distal region at a mouse chromosome long-arm site proximal to the centromere; and a telomere sequence, wherein the vector is stably retained in a cell and/or tissue of a mammal. In addition, disclosed are cells or non-human animals comprising the vector, and use of the cells or non-human animals.

Abstract: This invention relates to a mammalian artificial chromosome vector, which retains a human chromosome 7 fragment comprising human cytochrome P450 genes and is transmittable to progeny, wherein the human chromosome 7 fragment retains a region of approximately 1 Mb±500 Kb in size comprising at least a human CYP3A gene cluster, which region is located between chromosome markers AC004922 and AC073842, and to a non-human mammalian animal retaining the vector.

Abstract: Disclosed is a mouse artificial chromosome vector, comprising: a natural centromere derived from a mouse chromosome; a mouse-chromosome-derived long-arm fragment formed by deleting a long-arm distal region at a mouse chromosome long-arm site proximal to the centromere; and a telomere sequence, wherein the vector is stably retained in a cell and/or tissue of a mammal. In addition, disclosed are cells or non-human animals comprising the vector, and use of the cells or non-human animals.

Abstract: A chimeric non-human animal having an in vivo human hepatocyte population, wherein the effects of non-human animal cells on drug metabolism are suppressed or deleted is provided. A method for producing a chimeric non-human animal that lacks a drug-metabolizing system or has a suppressed drug-metabolizing system and is provided with a drug-metabolizing system driven by human hepatocytes, is provided. The method comprises transplanting human hepatocytes into a non-human animal characterized by (i) being immunodeficient, (ii) having liver damage, and (iii) lacking the functions of an endogenous Cyp3a gene.

Abstract: This invention relates to a human artificial chromosome (HAC) vector carrying a human chromosome-derived centromere, a subtelomere sequence, and a telomere sequence, to a human cell medicine or human cells comprising the HAC vector, to methods for preparing the HAC vector and human cells, and to methods for producing a therapeutic protein using the HAC vector.