Recently, TALEN-mediated HR was used to generate a floxed kcnh6a allele in zebrafish (Hoshijima et al., 2016). The loxP sites were provided by a donor plasmid that expressed the α-crystallin:Venus reporter gene, which was used to identify founders carrying the modified alleles with an overall germline transmission efficiency of 12% (Hoshijima et al., 2016). Using Zwitch in this study, we achieved a germline transmission efficiency of 59% and confirmed that 89% of alleles were in the correct non-mutagenic orientation (Figure 1E). The efficiency of the Zwitch method was likely enhanced by screening for the LG marker at two different time points (7 and 45 dpf), as this excluded false positives resulting from unintegrated targeting vectors at 7 dpf (Figure 1E). Moreover, the ability of Zwitch to be inserted at any location in the target intron allowed us to screen for the TALEN pair associated with the greatest HR efficiency (Figure 1B and C). This feature may facilitate the efficient generation of conditional alleles in other genes, as a high DSB rate increases the rate of HR at target sites, thereby increasing the likelihood of successfully generating conditional alleles via genome editing (Hoshijima et al., 2016).