A part of the answer may lie in the intrinsic properties of the DNA origami method and especially the scaffold staple excess strategy, which facilitates high-yield folding even for complex 3D architectures. Our study further highlights the crucial role of staple excess and scaffold concentration as key-factors driving rapid in situ self-assembly. Devised by Paul Rothemund, the concept of DNA origamis was published nearly 20 years ago in a breakthrough paper which, by concretizing the seminal ideas of Nadrian Seeman, revolutionized nanoscience and many fields of research. During two decades, DNA origami method has proved to be not only exquisitely programmable but also exceptionally robust. Our findings further underscore this robustness, revealing that DNA origami selfassembly naturally aligns with the ionic conditions optimized for biological function. The second part of the answer may lie in the fact that, although machine-made, synthetic DNA has the exact same chemistry as biological DNA. Knowing that biological systems have evolved to conditions optimizing their functioning, which includes proper ionic conditions compatible with dynamic DNA assembly/disassembly, it is perhaps unsurprising that the media developed for cell culture and maintenance are also fortuitously optimized for ultra-fast isothermal self-assembly of DNA origamis at 37 °C. In this study, we have focused on origamis made of structural DNA bricks only, but the method is readily compatible with the incorporation of modified staples to enrich their functionality, for instance toward the cellular interface. By enabling the formation of DNA origamis in situ within live-cell environments in minutes-timescale, this method is the ground for the creation of a new class of environmental DNA nanomachines self-assembling directly within biological systems to facilitate applications ranging from cell surface nanosensing to adaptive drug delivery and dynamic mechanobiological activation.