zinc finger nuclease

A zinc finger nuclease is an early kind of programmable DNA scissors built from protein parts. Before CRISPR, scientists could not just write an RNA address; they had to engineer a custom protein that grips a specific DNA sequence, then attach a cutter to it — painstaking but, for its time, revolutionary.

The tool combines two modules. Zinc fingers are small protein domains, each stabilized by a zinc ion, that each recognize about three DNA bases; strung together, several fingers read a longer target sequence. To this DNA-binding array is fused the cutting part of an enzyme called FokI. Because FokI must pair up to cut, two zinc finger nucleases bind opposite strands side by side and together make a double-strand break that the cell then repairs.

Zinc finger nucleases proved that targeted genome editing in human cells was possible and reached early clinical trials. Their drawback is difficulty: designing fingers for each new target is laborious, expensive, and not always reliable, which is why the far simpler CRISPR system largely displaced them.