DNAOrigami

DNA origami is a method for folding a long single-stranded DNA molecule into predetermined nanoscale shapes using hundreds of short staple strands. Developed by Paul Rothemund at the California Institute of Technology in 2006, it has become a central technique in structural DNA nanotechnology, enabling programmable, high-precision nanostructures.

A typical process uses a single-stranded scaffold, commonly derived from the M13 bacteriophage genome, which is folded into the target architecture by hundreds of short oligonucleotides called staples. Each staple binds to specific complementary regions on the scaffold, pulling the molecule into a designed path. Thermal annealing drives the assembly and stabilizes the final structure.

Design is aided by computer tools such as caDNAno, which provide a schematic representation and staple sequences. After synthesis, staples are mixed with the scaffold and subjected to gradual cooling; the product is usually purified and characterized by atomic force microscopy, transmission electron microscopy, or cryo-electron microscopy to confirm the intended geometry.

Two-dimensional origami yields flat shapes, while three-dimensional designs build multilayer and hollow structures. Developments include wireframe and brick-like approaches, and dynamic DNA origami that can reconfigure in response to environmental cues or bound molecules.

Applications span nanoscale templating for arranging nanoparticles, biosensing, programmable drug delivery, molecular devices, photonic materials, and catalysis. The method provides a versatile platform for organizing matter with nanometer precision and studying fundamental self-assembly processes.

Limitations include cost of staple synthesis, variable yields, and stability under physiological conditions. Ongoing research seeks to improve scalability, robustness, and in vivo compatibility, expanding potential applications in medicine, materials science, and nanotechnology.