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.

The present invention relates to recombinant adeno-associated virus (rAAV) delivery of polynucleotides for treating Duchenne Muscular Dystrophy resulting from the duplication of DMD exon 2. The invention provides rAAV products and methods of using the rAAV in the treatment of Duchenne Muscular Dystrophy.

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.

Compositions and regimens useful in treating phenylketonuria are provided. The compositions include recombinant adeno-associated virus (rAAV) with a transthyretin enhancer and promoter driving expression of a human phenylalanine hydroxylase.

This invention relates to selective inhibition of the alternative pathway (AP) of the complement system using an anti-factor D antibody. Specifically, the invention relates to methods of treating an AP-mediated disease or AP-mediated disorder in an individual by contacting the individual with an anti-factor D antibody.

Compositions and methods for in utero gene editing in mammalian lung cells are disclosed.

A genetically modified rodent is provided that comprises a modified Acvr1 gene that comprises a conditional altered exon 7 encoding R258G in anti sense orientation, flanked by site-specific recombinase recognition sites, wherein the altered exon is inverted to sense orientation upon action of a recombinase, resulting in ectopic bone formation.

Provided are compositions and methods of using engineered myogenic cells for delivery of an agent to an individual. Also provided are methods of producing reprogrammed myogenic cells from adult myogenic cells, and use of the reprogrammed myogenic cells for therapy and agent delivery.

The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

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.