The promise of DNA origami shows signs of coming to fruition a decade after its debut.
Science seeks to understand the mechanisms of nature, to develop tools of investigation and to make useful and sometimes revolutionary things with which to build our future. And every now and again, a piece of science comes along that seems like a work of art.
All of this was exemplified by a research paper published in Nature ten years ago that, literally, produced smiles (see Nature 440, 297–302; 2006). Using an astoundingly simple and general method to assemble strands of DNA into arbitrary shapes, the research generated ‘smileys’ that graced the cover of Nature and announced the arrival of DNA origami to the world.
The robustness of this method changed the game for DNA nanotechnology, which has since developed at an astonishing pace. It is a beautiful demonstration of how science can progress.
The concept behind DNA origami was laid down in the early 1980s by crystallographer Nadrian Seeman, who realized that the ability of DNA molecules to carry and transfer information according to strict base-pairing rules could be used to rationally assemble structures with precisely controlled nanoscale features.
This unprecedented level of programmability makes DNA a unique building material. Nanodesigners have embraced the biomolecule to fabricate intricate tiled patterns, boxes with lids that can be opened and arrays of precisely located binding elements that can incorporate proteins, dyes and other functional materials into regular lattices.
Pivotal to the success of DNA as a nanoscale building material have been automated methods to synthesize short DNA molecules of any sequence. A detailed understanding of how base-pairing translates into the formation of DNA double helices has also been crucial. Such helices control the shapes into which DNA molecules with given sequences will fold.
DNA origami provides the missing ingredient: a versatile yet straightforward assembly method. Computer-aided design programs determine how DNA scaffolds can be folded to realize desired structures, as well as which short DNA strands, or staples, are needed to hold the structures in shape.
Individual structures can also be assembled into more complex patterns, and sites that bind to functional materials can be introduced at any position.
The many eye-catching structures that have been built have pleased those of us with an appreciation of beauty. But even the most creative science will ultimately face the question: what is the point?
DNA nanotechnology has long searched for relevance. It is unrivalled in its ability to build complex structures with near-atomic precision, but the results tend to be labile, soft and so small that it is a challenge to put them to practical use.
Yet applications that address basic problems in science have emerged. DNA structures can serve as tools for determining the structures of proteins or as templates for assembling electronic components and basic devices. Responsive DNA structures can target diseased cells, and artificial membrane channels formed from DNA can act as single-molecule sensors.
Real-world applications might become feasible through recent developments — for example, improvements to the folding process that reduce assembly time and boost yield. Initial steps have also been taken to efficiently pair DNA nanostructures with technologically relevant substrates.
Many challenges remain, and DNA nanotechnology is far from maturity. But a growing number of scientists are entering the field to make more than just art. Watch this space.
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Practical DNA. Nature 531, 276 (2016). https://doi.org/10.1038/531276a