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22 May 2019 by Christine Stevenson

DNA origami: from novelty item to novel applications

There’s nothing mysterious about the name given to the practice known as DNA origami. The technique is exactly what it sounds like: the art of folding DNA. There is, however, a great deal of scientific intrigue about the practice, which may be on the verge of a big payout.

Like the ancient art of paper folding, DNA origami entails creating meticulously designed structures composed of DNA molecules folded into very specific two- and three-dimensional shapes.

Unlike its macroscopic namesake, however, scientists have been working hard for years to promote DNA origami beyond its origins as an art form.

Little more than a decade after the idea of DNA origami was unveiled to the world, the technique finds itself in a position to finally take on some practical applications.

When DNA origami was the subject of Nature’s cover story in March of 2006 the practice was, if not an art, a scientific novelty item.

The foundations of the idea were proposed in 1982 by the father of DNA nanotechnology Nadrian Seeman, but DNA origami as it is known today was detailed in a much more recent paper by Caltech professor Paul Rothemund. His original paper described the self-assembly of DNA molecules into two-dimensional shapes.

This included everything from straightforward structures like squares and rectangles, to whimsical stars and smiley faces, to larger more complex structures like pixel lattices and a primitive map of the western hemisphere.

What set Rothemund’s DNA origami apart from previous instances of structure-building with DNA was that the technique could be completed in a single step. Multiple reactions and purifications were not required; specific stoichiometric ratios didn’t need to be implemented.

The way that it was done (and continues to be done) is to coax a long strand of tailor-made DNA to fold with the assistance of short “staple” strands that hold it in a specific orientation. All strands are poured into the same reaction and automatically fold into the desired structure.

Since the invention of the method, increasingly complex three-dimensional structures have been produced. These structures have varied widely in utility, ranging from DNA in the shape of a bunny to a DNA box that can lock or unlock in accordance with environmental signals.

More sophisticated software has been developed to facilitate the design of DNA origami structures and other groups are developing improved methods for scalable production of DNA origami strands.

Propelled by these advances, DNA origami is starting to turn out some very promising solutions to problems in multiple fields. In biomedicine, DNA origami structures are being explored as drug delivery mechanisms.

Research in animal models has confirmed that stably-designed DNA structures can be used to package small molecules or antibodies, permeate a cell target, and release their therapeutic cargo.

Some of these structures have been outfitted with logic gates so complex that they warrant the title of “DNA robots.” Although preclinical, DNA origami drug delivery has proven to enhance the uptake of cancer drugs and can even sidestep certain types of drug resistance, which has been an ongoing challenge in cancer therapeutics.

DNA origami has also found some niche applications in materials science and technology. DNA origami has been used as the basis for formulating new materials with novel properties at the nanoscale.

It has been used to create cholesteric liquid crystals as well as colloidal solutions for assembling other particles and bulk materials.

DNA origami nanotubes have also successfully been used to affix cell membrane proteins in the proper alignment so that NMR can be used to determine their structure, a task that is tricky (if not impossible) for many membrane-bound proteins.

So is DNA origami the key to solving intractable protein structures? Will it be a solution to drug resistant cancers? Will it enable the creation of new materials with never-before-seen properties and uses?

As the supporting software, synthesis, and other technology continue to improve, it seems that DNA origami’s killer application could come from almost anywhere and that we may not have to wait long to find out what it will be.