Abstract: The present disclosure relates to methods for regulating cholesterol efflux in retinal pigment epithelium cells and treating or preventing a neurodegenerative disease or disorder (e.g., macular degeneration).

Abstract: The present disclosure relates to methods, compositions, and systems for rescuing gene function and the treatment and prevention of a disease or disorder (e.g., bestrophinopathies).

Abstract: The present disclosure provides vectors comprising a transgene(s) encoding more than one isoform of Crumbs homologue-1 (CRB1) (e.g., CRB1-A and CRB1-B), and compositions thereof, for use in the treatment or prevention of CRB1-related diseases and disorder (e.g., autosomal recessive retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA)).

Abstract: The present disclosure relates to methods and compounds for reprogramming metabolism in one specific retinal and neuronal cell type leading to improved cell and tissue survival and function. In particular, the present disclosure relates to increasing PGC1?/Pgc1? or NRF2/Nrf2 or inhibiting HIF/Hif or KEAP1/Keap1 to reprogram metabolism and survival of cells in a variety of neurodegenerative conditions, and specifically those which cause blindness.

Abstract: The present disclosure relates to methods and compounds for promoting anabolic pathways in neuronal cells leading to improved neuronal survival. In particular, the present disclosure relates to inhibiting PHD to promote glycolysis and neuronal survival in a variety of neurodegenerative conditions such as retinitis pigmentosa.

Abstract: The present disclosure provides vectors comprising a transgene(s) encoding more than one isoform of Crumbs homologue-1 (CRB1) (e.g., CRB1-A and CRB1-B), and compositions thereof, for use in the treatment or prevention of CRB1-related diseases and disorder (e.g., autosomal recessive retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA)).

Abstract: The present disclosure provides for systems and methods to limit the duration of a gene editing machinery, such as an endonuclease system. A self-terminating mechanism may be introduced by placing one or more target sequences (targeted by the gene editing machinery) on a polynucleotide encoding at least one component of the gene editing machinery/system.

Abstract: The present disclosure provides methods for treating autosomal dominant diseases in a subject. In some aspects, the methods involve the use of a gene editing enzyme with a pair of unique guide RNA sequences that targets both mutant and wildtype forms of autosomal dominant disease-related gene for destruction in cells, and then supplying the cells with wildtype autosomal dominant disease-related gene cDNA which is codon modified to evade recognition by the guide RNAs. These methods are broadly applicable to any autosomal dominant disease.

Abstract: The present application discloses cellular models for diseases of the eye. In addition, the present application discloses methods and compositions for treating or preventing diseases of the eye.

Abstract: The present disclosure relates to methods and compounds for promoting anabolic pathways in neuronal cells leading to improved neuronal survival. In particular, the present disclosure relates to inhibiting YHL/Vhl to promote glycolysis and neuronal survival in a variety of neurodegenerative conditions, and specifically in retinitis pigmentosa.

Abstract: The present disclosure provides methods for treating autosomal dominant diseases in a subject. In some aspects, the methods involve the use of a gene editing enzyme with a pair of unique guide RNA sequences that targets both mutant and wildtype forms of autosomal dominant disease-related gene for destruction in cells, and then supplying the cells with wildtype autosomal dominant disease-related gene cDNA which is codon modified to evade recognition by the guide RNAs. These methods are broadly applicable to any autosomal dominant disease.