On dna Nanotechnology and DNA nanotechnology

It’s all about what syllable you put the accent on. I’m just coming back from the AAAS meeting, where we had a most awesome Symposium on Nucleic Acid Nanotechnology. I sort of meant this both as a swan song for my tenure as President of the ISNSCE (go, Hao!) and as a coming-out cotillion for DNA nanotechnology. The world needs to know what is happening in this amazing field.

Right before the Symposium (which was attended by … dozens!) I got to hear Chad Mirkin from Northwestern speak. As always, Chad’s talk was awesome. He is a genius at both coming up with new approaches and applications, and at marketing these. For example, we learned that spherical nucleic acids (SNAs) are the logical next step in the progression from linear nucleic acid through circular nucleic acid. And we know how long it took to make the wheel with DNA, so SNAs are really taking us out of the molecular biology Stone Age. Once Chad discovers kinetics we’ll likely have a *fourth dimension* of nucleic acid structure, sort of a time tesseract of DNA. Maybe a time-traveling cubic lattice, who knows?

Anyway, Chad’s work, as impressive as it is, is dna Nanotechnology. The accent is on the Nano, not the DNA. As it should be, there’s lots of fun things you can do with nucleic acids as smart glues. But for me this just puts into sharper relief the DNA nanotechnology community, in which the accent is on the DNA.

As speakers, we had Ned Seeman, who as always gave a great historical and contemporary perspective on the power of using nucleic acids as building materials. Ned continues to emphasize that this is how we control the structure of matter from the atomic level upwards, and he continues to be right. He presented some exciting results on determining the structures of nanocrystals, and may be on the verge of realizing the dream he started in the early 1980s, using DNA as a scaffold for solving molecular structures. He was followed by William Shih, who showed an actual example of using DNA as a … well, not a scaffold, but an organizer … for solving a NMR structure. William also did his 3D Origami thang, but took it into new dimensions, so to speak, by examining the impact of DNA shape on cellular uptake. Finally, Erik Winfree made a strong case for embedded molecular programming, with DNA as the avatar for a world where we have not just Bluetooth enabled toothbrushes (wow, Erik, I didn’t believe you: http://www.geekosystem.com/bluetooth-toothbrush/), but toothbrushes that may directly interact with the bacteria they find, via molecular programming.

And this leads me to our other speaker, Greg Heath, from Illumina, who actually kicked off the proceedings. The NextGen revolution continues to consume us all, and I think it was modestly incongruous for folks to see this amazing commercial enterprise, which is impacting human health in a very immediate way, juxtaposed with DNA nanotechnology. As Ned leaned over to me to whisper, during the lively Q&A that followed Greg’s talk, “What the heck am I doing here?” Except, of course, it was Ned, and he didn’t say “heck.”

But to me, that was the point, that juxtaposition. In the frame tale that I tried to loosely wrap around these proceedings, it is the fact that we now know the biological world with single molecule, digital resolution that makes DNA nanotechnology ever-more-important. It is the possibility that the knowledge of every goddamn molecule in you will not just translate into electrons and information, but into actuation via molecular programming. Ned’s and William’s and Erik’s dreams really are the dreams of Wally Gilbert and Frederick Sanger. When there are nanotheranostic systems, they will undoubtedly be actuated in part by sequence, via the structural and programming tools these researchers have given to us.

One problem, of course, is that unless you’re working inside a cell with a ready supply of DNA, or have some other replicating nanotech, DNA is not the world’s best (and certainly not the world’s cheapest) material. This is where Chad’s dna Nanotechnology gets it right, we have to use the adhesive, self-assembly, programming, and sequence recognition properties of nucleotides, but we have to do it with something that isn’t so much nucleotides. As I have said elsewhere, we are primed for a next generation of materials based on nucleotides, where the backbones are … something different. Maybe peptides, maybe vinyl (http://www.ncbi.nlm.nih.gov/pubmed/22614385), maybe some other polymer. But definitely more rugged and more readily synthesized in bulk. As they should have said in The Graduate:

Older fart: I just want to say one word to you. Just one word.
Young Turk: Yes, sir.
Older fart: Are you listening?
Young Turk: Yes, I am.
Older fart: Replicating Plastics.
Young Turk: Exactly how do you mean?

Ah, yes, exactly how.


- originally posted on Sunday, February 24th, 2013