When DNA meets LEGO: Sculpting on the Nanoscale

Think back to your childhood, and there’s one thing many of us had in common: LEGOs. In fact, I challenge you to find someone who has never played with LEGO bricks in their lifetime. From houses to spaceships, the possibilities are seemingly endless with these colorful bricks. Now, think of your favorite LEGO creation, and imagine it miniaturized 4 million times, Magic School Bus style. That is what researchers at Harvard University have accomplished. Instead of using plastic pieces, Peng Yin’s team of scientists created bricks out of the building blocks of life: DNA. DNA, you may remember from high school science classes, are the molecules that make up our genetic code.

You may wonder what the purpose of these nanoscopic DNA sculptures are. Why spend time creating tiny, ‘invisible’ Teddy bears? Although the shapes created in the current study were for proof-of-concept purposes, it opens up many possibilities for the development of nanotechnologies. For example, hollow DNA boxes can be used as vehicles for administering medications. Unlike traditional methods of drug delivery, DNA can be programmed to target specific locations or cell-types in the body, and in turn minimize side-effects to the surrounding tissues. Outside of medicine, there are talks of using DNA as the building material for the next generation of nano-sized computer chips.

These miniature DNA LEGO “bricks” were created using short strands of DNA, which have been designed to interlock with other DNA bricks – similar to how LEGO pieces can be locked together. By joining different combinations of DNA bricks together, many designs can be made. Unlike LEGO pieces, DNA bricks are so small that they are invisible to the naked eye, and can only be seen under a microscope that magnifies the block 50,000 times! However, seeing the bricks is only half the battle. Scientists then looked to nature for inspiration on how to assemble them.

DNA is a polymer, meaning that it is a large molecule made up of smaller molecules, similar to beads on a string. Each “bead” is called a base, and there are four unique bases that make up the DNA of every living thing – Adenine (A), Guanine (G), Thymine (T), and Cytosine (C). The order of these bases determines the characteristics of each individual. Although DNA can exist in this single stranded form, it is much more stable as a double stranded helix. That is, when two strands of DNA pair together to form a ladder-like structure. Each base has a preferred partner – A always pairs with T, and C always pairs with G. The rungs of this DNA ladder are the pairs bases holding the ladder rails together. The life of a DNA molecule is spent in a constant search for a matching partner.

With this knowledge in mind, Yin’s group designed and created over 30,000 single-stranded DNA molecules, Each molecule is 52 bases long, and forms into the same general brick shape. At the molecular level however, each DNA brick is made of a unique sequence of bases, and therefore has unique requirements when searching for its complementary brick. These molecules are designed such that upon finding the right partners, the slurry of DNA join together, and forms into a massive cube containing up to 30,000 DNA bricks. Remarkably, this entire process happens automatically, dictated solely by the sequence of DNA. Because the exact location of each brick within the cube is known, different shapes and patterns can be created by leaving out specific bricks from the full set. By chipping away at these DNA blocks, researchers are able to create a seemingly unlimited number of miniature DNA sculptures, limited only by one’s imagination. In this study, the researchers built a Teddy bear, a rabbit, and the word “LOVE”. This technology offers new and exciting tools for the field of nanotechnology, for applications in medicine and computing.