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Lego-like DNA Building Bricks
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November 30, 2012
Using short pieces of single-stranded DNA, scientists have created a library of self-assembling, Lego-like DNA building blocks. These blocks snap together to create tiny, 3D nanostructures that could one day be used for smart drug delivery.
“With this modular architecture, once you synthesize a collection of DNA bricks that define a 3D cube, you just need to choose from the bricks that you already synthesized to make a new shape,” said Harvard Medical School assistant professor Peng Yin who developed the new system. “Designing a new shape is reduced to simply picking and mixing existing strands.” Scientists have previously used DNA as nanoscale building material, but the process was complex and time-consuming. In 2006, a simpler method—called DNA origami—was introduced. The technique used a scaffold folded into shapes via interactions with hundreds of smaller DNA strands—nicknamed staples. For each new DNA origami shape, an entirely new scaffold and set of staples must be designed and manufactured.
But in a new paper published in Science (1), Harvard postdoc Yonggang Ke and colleagues describe a modular two-stud DNA brick system for building nanostructures.
The bricks are created by folding a single strand of 32 nucleotides in half. Each brick contains four domains that consist of eight nucleotides. Two tail domains act like two plugs on a Lego block, while two head domains act like two holes into which other plugs are inserted.
Each domain is complementary to a domain on some other DNA brick. So, when the bricks are thrown into the same pot with one another, they hybridize and self-assemble to form a larger, pre-designed cube—a so-called 3D molecular canvas.
“We have a very simple architecture and simple motif and simple binding rules. That’s a major advantage,” said Yin. The cube canvas is like a blank slab of marble from which intricate nano-sculptures can be carved.
Because the cube is modular, individual bricks can be removed without the whole structure collapsing. Using 3D modeling software, scientists can design a desired shape by removing certain voxels—eight base-pair blocks—from the cube. The program lists the strands needed to form the shape. An automated liquid-handling robot mixes the correct strands together, and they self-assemble.
Using agarose gel electrophoresis and transmission electron microscopy, the team can see the 102 shapes that they have constructed, including block letters, a skull, and various structures pockmarked with intricate cavities and tunnels.
Yin hopes to use this technology to carry drugs to tumors or barcode molecules during experiments. “Importantly, we want to go from structure and shape to functions,” said Yin. “We decided to go against prevailing wisdom with this work.”
It worked so well that now he wants to understand “the biophysical mechanisms that underlie the formation of these structures. I was surprised to see how well it works.”
1. Ke, Y., L. L. Ong, W. M. Shih, and P. Yin. 2012. Three-Dimensional structures Self-Assembled from DNA bricks. Science 338(6111):1177-1183.
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