A method of constructing humanized murine model using stem cells, includes obtaining human stem cells; transplanting human stem cells into murine with liver damage; and obtaining hepatotropic virus infected humanized murine. It was found that by inducing severe liver damage and transplanting human stem cells, human-derived hepatocytes in murine liver have a high chimeric rate of 50-95%, and human-derived immune cells may exist in murine organs such as spleen, blood, liver, and bone marrow, thereby forming murine model of humanized liver and immune cell. The humanized murines are then infected with various types of hepatotropic viruses to form humanized hepatotropic viral infected murine model. In addition to construction of model for studying hepatotropic viral infection using the technique for constructing the humanized murine model, the concept of this technical solution may also be used for constructing models of other humanized organs.

A method for producing a new deafness model animal and a new deafness model animal produced by the method, enabling research that can also be applied to clinical application to a human. The present invention provides a method for producing an acoustic trauma deafness model animal, the method including exposing a non-human primate animal to a sound having a frequency of 1 kHz to 32 kHz and a sound pressure level of 100 dB to 150 dB for 10 minutes to 360 minutes. In addition, the present invention provides an acoustic trauma deafness model animal provided by the method for producing an acoustic trauma deafness model animal.

Provided herein are screening methods and animal models related to intraocular diseases such as age-related macular degeneration (AMD), for example, for identifying candidate therapeutics for treating or preventing eye diseases, such as AMD. Also provided herein are compounds/compositions that are useful for killing or inhibiting the growth of a microorganism, such as Bacillus megaterium. Further provided herein are methods of using the compounds/compositions for treating infections with a microorganism, such as Bacillus megaterium and for treating or preventing diseases or disorders associated with such infections, such as AMD.

Artificial expression constructs for modulating gene expression in targeted central nervous system cell types are described. The artificial expression constructs can be used to express synthetic genes or modify gene expression in GABAergic or glutamatergic neurons within the thalamus. In some cases, the artificial constructs can also be used to express synthetic genes or modify gene expression in neurons within the thalamus as well as a secondary cell type.

An object of the present invention is to provide a method for producing a non-human primate model of AMD, a method for evaluating the efficacy of a test substance in the prevention or treatment of AMD using the AMD animal model produced according to this method, and a method for screening substances effective in the prevention or treatment of AMD using the aforementioned AMD animal model. The method for preparing the AMD animal model consists of administering sodium iodate into a vitreous body of a non-human primate, and the method for evaluating the efficacy of a test substance in the prevention or treatment of AMD consists of preparing a non-human primate model of AMD according to the aforementioned method for preparing an AMD animal model, and evaluating the efficacy of the test substance in the prevention or treatment of AMD using the resulting AMD animal model.

Provided for the first time in the present invention is a method for preparing a non-human primate somatic cell cloned animal, which method specifically comprises the steps of: (i) providing a reconstructed egg, wherein the egg comes from the non-human primate (ii) activating the reconstructed egg to form an activated reconstructed egg or activated reconstructed embryo formed by the reconstructed egg; (iii) reprogramming (a) the activated reconstructed egg or (b) embryonic cells of the activated reconstructed embryo to obtain a reprogrammed reconstructed egg or reprogrammed reconstructed embryo; and (iv) regenerating the reprogrammed reconstructed egg or reprogrammed reconstructed embryo to obtain the non-human primate somatic cell cloned animal. The method of the present invention can significantly improve the developmental capacity of nucleus-transplanted embryos in non-human primates (such as monkeys).

Provided herein are screening methods and animal models related to intraocular diseases such as age-related macular degeneration (AMD), for example, for identifying candidate therapeutics for treating or preventing eye diseases, such as AMD. Also provided herein are compounds/compositions that are useful for killing or inhibiting the growth of a microorganism, such as Bacillus megaterium. Further provided herein are methods of using the compounds/compositions for treating infections with a microorganism, such as Bacillus megaterium and for treating or preventing diseases or disorders associated with such infections, such as AMD.

Compositions and methods for improving embryo development, treating idiopathic male factor infertility, and enabling infertile/sub-fertile/sterile men to father their own genetic offspring are provided. Typically, the methods include administering into a male or female gamete or fertilized embryo an effective amount of a compound that increases bioavailability of a TET protein to improve development of an embryo resulting from fertilization of the female gamete by a male gamete. The compound can be administered into the gamete or embryo before, during, or after fertilization. The compound can be administered by an injection such as intracytoplasmic injection. The compound and the male gamete can be administered in combination by intracytoplasmic sperm injection. Methods of making male gametes, and methods of modifying the genome of a male gamete or embryo using an effective amount of a gene editing composition to correct a gene mutation or anomaly in the genome thereof are also provided.

Provided is a primate disease model construction method based on fast gene edition, which including (a) constructing a sgRNA expression plasmid by using a gRNA oligonucleotide and a pX330 plasmid; (b) injecting the sgRNA expression plasmid prepared in step (a) into a hepatic portal vein of a primate animal by using a biopsy needle until liver cells become cancerous for obtaining a primate disease model. The sgRNA expression plasmid constructed by the gRNA oligonucleotide and pX330 plasmid can be directly injected into the primate liver tissue, so as to construct a tumor model rapidly.

Provided herein are rAAV and other vectors and compositions useful for treating a patient having CMT2 comprising: (a) a recombinant nucleic acid sequence encoding an engineered human mitofusin 2 coding sequence operably linked to regulatory sequences which direct expression thereof in a human target cell. Also provided are rAAV and other vectors and compositions useful for treating a patient having CMT2 comprising: (b) a nucleic acid sequence encoding at least one miRNA specific for an endogenous human mitofusin 2 sequence in a human CMT2A subject, wherein the miRNA coding sequence is operably linked to regulatory sequences which direct expression thereof in the subject. Further provided are compositions containing both the engineered hMfn2 coding sequence and the at least one miRNA coding sequence, wherein the engineered human mitofusin 2 coding sequence has a sequence which differs from endogenous human mitofusin 2 in the CMT2A patient in the target site of the encoded miRNA.