The present disclosure relates to genetically modified non-human animals (e.g., genetically-modified mice or rodents) that express a hACE2 and/or hTMPRRS2 under control of the mouse promoter and the genetically modified non-human animal does not express native ACE2 and/or hTMPRRS2. The present disclosure also relates to methods of generating the genetically-modified animals (e.g., genetically modified mice or rodents), and methods of using the genetically modified non-human animals (e.g., genetically modified mice or rodents) described herein.

A genetically modified non-human animal comprising a genome containing an endogenous non-human ACE2 locus genetically modified to encode a complete human ACE2 gene. According to a further embodiment the genome is genetically modified to encode a second, a third, and a fourth complete human ACE2 gene, the human ACE2 gene is at least 85 percent identical to SEQ ID No: 1, the animal of is a mouse, the human ACE2 gene encodes six protein variants, an endogenous Tmprss2 gene is unmodified, a LoxP gene flanks each of a 5′ and a 3′ end of a nucleic acid sequence of the human ACE2 gene, and the human ACE2 gene is expressed in a lung, kidney, spleen, stomach, liver, intestine, heart, and skeletal muscle of the animal, and a cortex, striatum, middle brain, hippocampus, olfactory bulb, and cerebellum of a brain of the animal.

A nucleic acid molecule can code for an Orf virus vector promoter. A recombinant Orf virus vector can be included in a cell. The nucleic acid molecule, the vector and/or the cell can be included in a composition. The recombinant Orf virus vector can be used for the production of a foreign gene.

A nucleic acid molecule can code for an Orf virus vector promoter. A recombinant Orf virus vector can be included in a cell. The nucleic acid molecule, the vector and/or the cell can be included in a composition. The recombinant Orf virus vector can be used for the production of a foreign gene.

Disclosed herein are methods for producing virus-infected cell lines or animal models, wherein an enveloped virus including a lipid bilayer is mixed with a bile acid or a bile acid derivative, which allows the lipid bilayer to be replaced with a lipid bilayer derived from a target animal. Also disclosed herein are the virus-infected cell lines or animal models so produced and methods of screening a therapeutic candidate for a viral disease using the same.

The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of: (i) transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes a urokinase-type plasminogen activator operably linked under the control thereof; (ii) injecting the transformed mouse ES cells obtained in step (i) into a host embryo; (iii) transplanting the host embryo obtained in step (ii) via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse; and (iv) crossing the chimeric mice obtained in step (iii), so as to obtain a transgenic mouse in which the DNA fragment is introduced in a heterozygous form.

The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of: (i) transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes a urokinase-type plasminogen activator operably linked under the control thereof; (ii) injecting the transformed mouse ES cells obtained in step (i) into a host embryo; (iii) transplanting the host embryo obtained in step (ii) via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse; and (iv) crossing the chimeric mice obtained in step (iii), so as to obtain a transgenic mouse in which the DNA fragment is introduced in a heterozygous form.

Compositions and methods are provided for modulating adeno-associated virus (AAV) infection. For example, compositions and methods are provided for enhancing permissiveness of a target cell to AAV infection (e.g., by increasing levels of AAVR (KIAA0319L) in the cell), for reducing permissiveness of a target cell to AAV infection (e.g., by reducing levels of AAVR in the cell), and for nucleic acid delivery (e.g., by (i) increasing permissiveness of a target cell to AAV infection, e.g., by increasing the amount of AAVR in the cell; and (ii) contacting the target cell with an AAV particle that includes a nucleic acid of interest). Also provided are screening methods and kits for practicing the methods of the disclosure.

A nucleic acid molecule can code for an Orf virus vector promoter. A recombinant Orf virus vector can be included in a cell. The nucleic acid molecule, the vector and/or the cell can be included in a composition. The recombinant Orf virus vector can be used for the production of a foreign gene.

The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of: (i) transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes a urokinase-type plasminogen activator operably linked under the control thereof; (ii) injecting the transformed mouse ES cells obtained in step (i) into a host embryo; (iii) transplanting the host embryo obtained in step (ii) via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse; and (iv) crossing the chimeric mice obtained in step (iii), so as to obtain a transgenic mouse in which the DNA fragment is introduced in a heterozygous form.