Methods are disclosed for correcting a mutant allele of a gene of interest in a primate cell. The methods include a) introducing a non-naturally occurring targeted nuclease and site-specific nucleotide-binding guide that act together to introduce double-stranded breaks in the mutant allele into the primate cell, wherein: i) the primate cell is undergoing mitotic cell division; ii) the primate cell comprises a genome that is heterozygous for the mutant allele, such that the genome comprises one copy of the mutant allele and one copy of a wild-type allele; iii) single-stranded oligonucleotides homologous to the wild-type allele are not introduced into the primate cell. The methods also include b) allowing the primate cell to activate homology-directed repair of the double-stranded DNA breaks in the mutant allele, thereby correcting the mutant allele using the normal wild-type allele as a repair template and producing a primate cell that is homozygous for the wild-type allele. The primate cell can be a one-cell embryo and/or a human cell.

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).

Persistence of HIV in anatomic sanctuary sites such as the brain prevents viral eradication. Although combination antiretroviral therapy (cART) inhibits viral replication to undetectable level by standard clinical assay, it does not selectively eliminate virus reservoirs. To target HIV reservoirs, the present inventor developed an HIV Rev-dependent lentiviral vector carrying a series of therapeutic genes, such as diphtheria toxin, anthrolysin O from Bacillus anthracis, human TRAF6, or the herpes simplex 1 virus thymidine kinase gene (HSV-tk). The present disclosure provides the Rev-dependent vectors for targeting viral reservoir in a SIV/rhesus macaque model. SIV-infected rhesus macaques were first treated with cART for over 6 months starting 12 weeks post infection, followed by injections with viral particles assembled from a SIV Rev-dependent vector carrying HSV-tk. Following particle injection, animals were further treated briefly (two weeks) with ganciclovir (GCV), which induces the killing of SIV+, HSV-tk expressing cells. cART was terminated following the GCV treatment, and there was observed a partial control of viral rebound over a period of 4 months after cART cessation. The animal was further treated with additional Rev-dependent vector particles, and viral load was diminished to the undetectable level for over 1 year in the absence of any treatment. These results suggest that the Rev-dependent vector, with or without a functional gene, has the potential to diminish viral reservoirs in vivo and can offer a cure of functional cure of HIV/SIV infection.

A non-human primate restraint system comprising a complex of a manipulating chamber and a restraint chamber. The system provides a humane, interactive, and safe structure and methods for leading non-human primates from a chute or a cage, through the manipulating chamber, and into a restraint chamber. The restraint chamber is removably attached to the manipulating chamber. The restraint chamber has an upper part with a screen, a middle portion with slots to accommodate platforms, and a lower section with a screen. The screens can be retracted or removed to access either the top portion or lower portion of the NHP.

Provided here are certain recombinant HIV compositions and animal models to evaluate prophylactic and therapeutic antiviral compositions.

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.

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 are methods and composition for treating certain neurodegenerative diseases, such as RGC loss-related degenerative disease and Parkinson's Disease, using in vivo conversion of glial cells to neurons by PTB and optionally nPTB knock down via CRISPR/Cas delivered by AAV vectors.

Genetically modified cells, tissues, and organs for treating or preventing diseases are disclosed. Also disclosed are methods of making the genetically modified cells and non-human animals.

Aspects of the disclosure relate to a composition comprising 20-60% w/w of fat combined with a nitric oxide synthase inhibitor. Method aspects of the disclosure relate to a method for inducing heart failure with preserved ejection fraction in an experimental laboratory animal, the method comprising administering a composition of the disclosure or a composition comprising 10-60% w/w of fat and a composition comprising a nitric oxide synthase inhibitor to the laboratory animal.