DNA-binding platforms for artificial transcription factors. (a) Each repeat module of an engineered zinc finger protein recognizes three base pairs of DNA. The VP64 transcriptional activation domain is shown in cyan. Other common effector domains include the KRAB repression domain. (b) Each repeat of a TALEN protein recognizes one base pair of DNA. A thymine base (red) just 5′ of the repeat-bound DNA site is preferred for high-affinity binding. (c) An engineered CRISPR system consists of a guide RNA (red strand with colored sections) that directs the Cas9 nuclease (light blue) to the target DNA. Mutation of the two-endonuclease domains (arrows with red X) produces a non-catalytic DNA-binding domain, to which an effector domain can be attached. The required protospacer adjacent motif (PAM), NGG, is shown 3′ to the target site.