Genome engineering technologies based on synthetic nucleases and transcription factors enable the targeted modification of the sequence and expression of genes. These engineered nucleases and transcription factors typically consist of a DNA-binding domain linked to an effector module. Zinc finger proteins (ZFPs) and transcription activator-like effector (TALE) DNA-binding domains were discovered in nature and systems have been developed to engineer synthetic versions of these proteins with the potential to recognize any nucleotide sequence in the genome. More recently, RNA-guided targeting of DNA sequences through the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system has further simplified custom genome engineering, obviating the need for the complex protein engineering necessary for the ZFP- and TALE-based systems and therefore enabling widespread use of genome engineering. Effector modules that can be attached to targeted DNA-bindingdomainsinclude endonuclease catalyticdomains, transcriptional activators, and transcriptional repressors.