The present invention relates to a Pde6b-deficient animal model of retinal degeneration produced by engineered endonucleases, and a method for producing the same. In the animal model of retinal degeneration according to the present invention, only a specific target gene can be removed using engineered endonucleases, so that mutagenesis can be stably achieved. In addition, it is possible to produce a congenital animal model through genetic manipulation at the embryonic stage rather than through acquired factors, which allows for production of an animal model that uniformly exhibits symptoms of the disease in question without being influenced by other factors.

Disclosed herein are methods of using probes for high-throughput screening of guide RNA (gRNA) efficiency for Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRiSPR-associated (Cas)-based genome editing systems. Further disclosed herein is a humanized transgenic mouse model that recapitulates the severe DMD pathology of human patients. The mouse model may be used for determining the feasibility of CRISPR-based therapies for the correction of the human dystrophin gene by gene editing and methods of use.

The present disclosure provides transgenic nematode systems for assessing function of heterologous genes, their variants and drug discovery. The transgenic nematodes contain a heterologous gene that is inserted via homologous recombination at the native locus replacing and removing the nematode ortholog, wherein expression of the heterologous gene rescues function of the removed nematode ortholog and a transgenic control animal is provided. The heterologous gene may be further modified to provide a variant, such as a human clinical variant, whereby a transgenic test animal is provided. Those transgenic test animals are used in methods to assess function of the heterologous variant and drug screens to find therapeutic candidates reversing deviant activity back to wildtype.

The present disclosure provides immunodeficient NOD.Cg-Prkdc.sup.scid Il2rg.sup.tm.sup.1Wjl/SzJ (NSG™) mouse models that comprise an inactivated mouse Flt3 allele and, in some models, additional genetic modifications. These mouse models useful, for example, for superior engraftment of diverse hematopoietic lineages and for immune-oncology, immunology and infectious disease studies.

The invention provides for AAV vectors expressing the ANO5 gene and antioxidant therapy as methods of inducing muscle regeneration and a method of treating muscular dystrophy.

The invention provides compositions and methods for manufacturing pluripotent cells. In particular, the invention provides improved culture platforms for manufacturing pluripotent cells with ground state pluripotency.

Methods and compositions for inducing a plurality of mutations in transgenic Cas9 eukaryotes to model a neuronal disease or disorder. The invention further comprehends testing putative treatments with such models, e.g., testing putative chemical compounds that may be pharmaceutically relevant for treatment or gene therapy that may be relevant for treatment, or combinations thereof. The invention allows for the study of genetic diseases and putative treatments to better understand and alleviate a genetic disease or a condition, e.g., autism, autism-spectrum disease or disorder, obsessive-compulsive disorder, or psychiatric disorders.

The invention provides compositions and methods for manufacturing pluripotent cells. In particular, the invention provides improved culture platforms for manufacturing pluripotent cells with ground state pluripotency.

A genetically modified mouse is provided that comprises a conditional Acvr1 allele that comprises a mutated exon that, upon induction, converts to a mutant exon phenotype, wherein the mutant exon phenotype includes ectopic bone formation. Mice comprising a mutant Acvr1 exon 5 in antisense orientation, flanked by site-specific recombinase recognition sites, are provided, wherein the mice further comprise a site-specific recombinase that recognizes the site-specific recombinase recognitions sites, wherein the recombinase is induced upon exposure of the mouse to tamoxifen. Upon exposure to tamoxifen, the recombinase is expressed and acts on the RRS-flanked mutant exon 5 and places the mutant exon 5 in sense orientation and deletes the wild-type exon.

Disclosed is a dTAG system comprising a small molecule degraders of FKBP12-tagged proteins via recruitment of Von Hippel-Lindau E3 ubiquitin ligase (VHL) E3 ubiquitin ligase and uses thereof.