Triplex origami structures folded with rHS staples are stable at physiological pH and therefore compatible with most proteins. For example, plasmid-folded structures can be incubated with restriction enzymes after folding to remove the vector backbone (Fig. ). Furthermore, occupation of the major groove by a TFO can inhibit the activity of DNA-interacting proteins. Triple-stranded DNA resists degradation by DNase I, for example, as demonstrated by a densely triplexed single-fold rHS triplex origami structure. Almost no digestion was observed for this structure after 18 hours incubation with 2 U/mL DNase I at 37 °C (Fig. , Supplementary Fig. for nHS variant). In comparison, 1 U/mL DNase I degrades plasmid DNA and densely-packed conventional DNA origami structures within a few minutes to 1 hour 51 .