there was a fundamental problem: the vast majority of these enzymes recognized sequences that were only six or eight letters long—far too short to be useful. Those sequences occurred tens of thousands or even hundreds of thousands of times in the human genome, meaning that even if the nuclease could stimulate homologous recombination in one gene, it would shred up nearly the entire genome in the process. The cell would be destroyed before it ever had a chance to initiate DNA repair.