 Two separate methods have been demonstrated to decrease off-target cleavage for 3-finger ZFNs that target two adjacent 9-basepair sites.Other groups use ZFNs with 4, 5 or 6 zinc fingers that target longer and presumably rarer sites and such ZFNs could theoretically yield less off-target activity.A comparison of a pair of 3-finger ZFNs and a pair of 4-finger ZFNs detected off-target cleavage in human cells at 31 loci for the 3-finger ZFNs and at 9 loci for the 4-finger ZFNs.