In Science Magazine’s November 30 cover story, researchers at Harvard’s Wyss Institute reported that they had created 100 three-dimensional (3D) nanostructures using DNA building blocks that function like Lego® bricks—an advance from the two-dimensional (2D) structures the same team announced building a few months ago in Nature.
The Wyss team, led by Wyss faculty member Brian Wei, Ph.D., had previously described its nanofabrication technique, “DNA-brick self-assembly,” as method for building complex nanostructures out of short synthetic strands of DNA.
Called single-stranded tiles (SSTs), 42-base strands of DNA “building blocks,” similarly to Legos, could be programmed, the researchers said, to assemble themselves into precisely designed shapes, such as letters and emoticons, like a smiley face.
In the 2D technique, a “single-stranded tile” (SST) consists of a 42-base strand of DNA composed entirely of concatenated sticky ends and that binds to four local neighbors during self-assembly. The investigators implemented their strategy with a master strand collection that corresponded to a 310-pixel canvas, and then used appropriate strand subsets to construct 107 distinct and complex two-dimensional shapes, thereby establishing SST assembly as a simple, modular and robust framework for constructing nanostructures with prescribed shapes from short synthetic DNA strands.
As described by the Wyss Institute, the trick to creating the 3D structures required starting with smaller DNA bricks, about 32 bases long, which changes the orientation of every matched-up pair of bricks to a 90 degree angle—giving every two Legos a 3D shape. The team then used these bricks to build out in addition to up, eventually forming 3D structures, such as a 25-nanometer solid cube containing hundreds of bricks. The cube can then act as a “master” DNA “molecular canvas”; in this case described in the Science paper, the canvas was comprised of 1000 so-called “voxels,” corresponding to eight base-pairs and measuring about 2.5 nanometers in size.
To date, most DNA nano research has focused on the use of a single long biological strand of DNA, which acts as scaffold along which smaller strands bind to its many different segments to create shapes. This method, called DNA origami, is also being pursued at the Wyss Institute under the leadership of core faculty member William Shih, Ph.D.
But the novel building block method, the scientists say, with its modular architecture, sophisticated geometric control, and synthetic nature, will further expand the range of applications that nucleic acid technology has already started to address.
The step from 2D to 3D nanostructures moves the use of DNA nanotechnologies forward toward applications including “smart” medical devices that target drugs selectively to disease sites, programmable imaging probes, and templates for precisely arranging inorganic materials in the manufacturing of next generation computer circuits.
Harvard’s Wyss Institute was founded to discover the engineering principles that nature uses to build living things, and to harness these insights to create biologically inspired materials and devices that will revolutionize healthcare and create a more sustainable world. In medicine, the Institute aims to develop innovative materials, devices, and disease reprogramming technologies that emulate how living tissues and organs self-organize and naturally regulate themselves.