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Meganucleases are endodeoxyribonucleases that have a large recognition site, which occurs rarely, even in entire genomes. Consequently, they can be used as highly specific tools in genome engineering; for example, to modify or eliminate a particular gene.
Zinc finger nucleases have an established role in genome editing. Here, the authors report a strategy for identifying zinc finger nucleases that discriminate between desired targets and provide genome-wide specificity.