We conclude two findings: First, the ability of DNA origami to penetrate into large 3D cancer spheroids is governed by the origami size rather than their internal structure and flexibility as previously proposed.[28] Second, the apoptosis induction efficiency of origami – FasL nanoagents toward cancer spheroids is dictated by the attachment strategy of FasL to the DNA origami rather than the design of the underlying origami itself. The gene discussed is FASLG; the disease is cancer.