Arbitrarily complex 3D DNA nanostructures built from DNA bricks

Computer-generated 3D models (top) and corresponding 2D projection microscopy images (bottom) of nanostructures self-assembled from synthetic DNA strands called DNA bricks. (Image Credit: Yonggang Ke, Wyss Institute, Harvard University.)

This past May we posted news of a major advance in the toolkit for DNA nanotechnology. Researchers led by Wyss Institute core faculty member Peng Yin developed a very versatile, rapid, and inexpensive way to assemble arbitrarily complex 150-nm two-dimensional DNA nanostructures from 42-nucleotide DNA tiles. A hat tip to ScienceDaily for reprinting this Wyss Institute news release of another major advance from the same research group aided by another Wyss Core Faculty member William Shih “Researchers Create Versatile 3D Nanostructures Using DNA ‘Bricks'”:

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have created more than 100 three-dimensional (3D) nanostructures using DNA building blocks that function like Lego® bricks — a major advance from the two-dimensional (2D) structures the same team built a few months ago.

In effect, the advance means researchers just went from being able to build a flat wall of Legos®, to building a house. The new method, featured as a cover research article in the 30 November issue of Science [abstract], is the next step toward using DNA nanotechnologies for more sophisticated applications than ever possible before, such as “smart” medical devices that target drugs selectively to disease sites, programmable imaging probes, templates for precisely arranging inorganic materials in the manufacturing of next generation computer circuits, and more. …

Earlier this year, the Wyss team reported in Nature how they could create a collection of 2D shapes by stacking one DNA brick (42 bases in length) upon another.

But there’s a “twist” in the new method required to build in 3D.

The trick is to start with an even smaller DNA brick (32 bases in length), which changes the orientation of every matched-up pair of bricks to a 90 degree angle — giving every two Legos® a 3D shape. In this way, the team can use these bricks to build “out” in addition to “up,” and eventually form 3D structures, such as a 25-nanometer solid cube containing hundreds of bricks. The cube becomes a “master” DNA “molecular canvas”; in this case, the canvas was comprised of 1000 so-called “voxels,” which correspond to eight base-pairs and measure about 2.5 nanometers in size – meaning this is architecture at its tiniest.

The master canvas is where the modularity comes in: by simply selecting subsets of specific DNA bricks from the large cubic structure, the team built 102 3D structures with sophisticated surface features, as well as intricate interior cavities and tunnels. “This is a simple, versatile and robust method,” says Peng Yin, Ph.D., Wyss core faculty member and senior author on the study.

The DNA-brick technique capitalizes on the ability of DNA strands to selectively attach to other strands, thanks to the underlying “recipe” of DNA base pairs. …

Another method used to build 3D structures, called DNA origami, is tougher to use to build complex shapes, Yin said, because it relies on a long “scaffold” strand of DNA that folds to interact with hundreds of shorter “staple” strands – and each new shape requires a new scaffold routing strategy and hence new staples. In contrast, the DNA brick method does not use any scaffold strand and therefore has a modular architecture; each brick can be added or removed independently.

“We are moving at lightning speed in our ability to devise ever more powerful ways to use biocompatible DNA molecules as structural building blocks for nanotechnology, which could have great value for medicine as well as non-medical applications,” says Wyss Institute Founding Director Don Ingber, M.D., Ph.D.

The news release includes a video and an animation showing how the DNA strands self-assemble to build complex 3D objects.

This powerful advance should lead to programmable molecular arrangements for several applications. Any of a great variety of molecular species can be attached to DNA bricks and thus assembled into arbitrarily complex 3D configurations. What sorts of molecular species would give DNA bricks functionality that could be used to build a very primitive nanofactory? Where does this advance stand on the road to molecular manufacturing or productive nanosystems? Back in May of 2005 Chris Phoenix and Tihamer Toth-Fejel authored a report for the NASA Institute for Advanced Concepts (“Large-Product General-Purpose Design and Manufacturing Using Nanoscale Modules“, PDF) in which they proposed two different designs for a very primitive nanofactory based upon planar assembly, each using 5-nm molecular building blocks of unspecified composition, prepared by either chemical synthesis or self-assembly, and incorporating a few simple functional capabilities. Certainly one or more functions could be attached to either these 2.5-nm DNA voxels or the 25-nm larger structures comprising 1000 voxels. Can anyone see a way from this advance to a primitive nanofactory that could be used to build improved nanofactories, leading eventually to molecular manufacturing?
—James Lewis, PhD

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