Abstract: The disclosure features methods of correcting a mutation in the human beta-globin (HBB) gene in a cell or population of cells. The disclosure also features methods of increasing repair of a DNA double stranded break (DSB) in an HBB gene by the homology-directed repair (HDR) pathway. The disclosure also features compositions for use in the methods.

Abstract: The disclosure features systems and methods for correcting a mutation in the human beta-globin (HBB) gene in a cell or population of cells. The disclosure also features methods of increasing repair of a DNA double stranded break (DSB) in an HBB gene by the homology-directed repair (HDR) pathway. The disclosure also features compositions for use in the methods.

Abstract: The present invention relates to compounds useful as inhibitors of DNA-PK. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various diseases, conditions, or disorders.

Abstract: Compounds, methods of editing a target genomic region(s), methods of repairing of a DNA break via a HDR pathway, methods of inhibiting or suppressing repair of a DNA break via a NHEJ pathway, and methods of modifying expression of a gene(s) or protein(s) comprise administering to one or more cells that include one or more target genomic regions, a genome editing system and a DNA protein-kinase (DNA-PK) inhibitor disclosed herein. Kits and compositions for editing a target gene comprise a genome editing system and a DNA-PK inhibitor disclosed herein.

Abstract: The present invention relates to improved systems and strategies for the investigation of kinase activity in cells. More specifically, cell-based assay methods are provided that allow the phosphorylating activity of a kinase to be determined inside a cell. The invention also provides cell-based screening assays for identifying compounds that have the ability to modulate the phosphorylating activity of protein kinases. Modulators of kinase activity identified by the screening methods are also described, as are pharmaceutical compositions comprising these modulators and methods of using them for inhibiting or enhancing cellular responses triggered by kinase-mediated events.