Zinc Finger Nucleases (ZFNs) were the first widely used programmable DNA binding protein system. ZFNs are comprised of a chain of zinc finger proteins fused to a bacterial nuclease to produce a system capable of making site-specific double stranded DNA breaks to enable gene edits. The zinc finger proteins provide site specific DNA targeting as they each recognize a 3–4 base pair DNA sequence.
In ZFNs, a chain of zinc finger proteins are utilized to recognize a longer, more specific locus within the genome. The nuclease commonly used in ZFN technology, fused to this chain of zinc finger proteins, is FokI, which must dimerize in order to introduce a DSB. Therefore a pair of ZFNs are used together to target and cut the DNA.