Gene editing proteins offer an efficient means of knocking out, inserting and repairing nucleic-acid sequences in living cells. However, while gene-editing proteins can efficiently target pre-determined sequences, they can also cleave similar sequences throughout the genome, albeit with lower efficiency (so-called “off-target” editing). Many gene editing technologies include design constraints that limit the sequences that can be targeted, for example CRISPR-Cas9 requires a PAM sequence and TALENs require a thymine (T) in the zero position of the target site (“T0”). A recently described temperature-sensitive gene-editing protein with flexible linkers, NoveSlice, shares the T0 requirement, limiting the available target sites in regions of low sequence complexity. We sought to remove the T0 requirement of TALEN and NoveSlice through amino-acid substitution of key residues in the N-terminal region of the DNA-binding domain. We designed and synthesized constructs encoding NoveSlice and TALEN proteins comprising various N-terminal regions using site directed mutagenesis. We tested the gene editing efficiency of these novel proteins by mRNA transfection into primary human keratinocytes. After 48 hours we amplified the target site, a region near the COL7A1 exon 73 splice acceptor site, and assessed editing using T7 endonuclease I. From this initial screen, we identified the most promising N-terminal region that had the highest editing efficiency in a target site with an N0. Surprisingly, when measuring cutting of an N0-containing target site, we observed “off-target” editing by TALENs while there was no editing by NoveSlice under these same conditions. Thus, the NoveSlice gene-editing protein showed a higher degree of specificity when compared to TALENs for this clinically relevant target site. These data suggest that the NoveSlice gene-editing protein can yield higher specificity than TALENs targeting the same site in primary human cells, and thus could offer an advantage in the development of both ex-vivo and in-vivo gene editing therapies.