Kids of all ages love to play with blocks and Legos, using them to construct buildings, cars, planes, roads, Death Stars, and so much more. Scientists and engineers are the same way! In the last twenty years, it has become possible to create individual blocks that are so tiny they’re on the nanometer scale. A length of 1 nanometer (nm) contains only about 20 atoms—imagine the width of a single human hair split into 30,000 pieces!  As exciting as it is that we can create a single nanoscale object which has never been seen in nature and design it to do something unique, one of the very big questions we still need to answer is how we can take these individual blocks and assemble them into bigger structures, like we do with Legos.

One approach to this problem exploits a phenomenon called self-assembly, which is the natural tendency of some molecules to form complex structures under the right conditions. Snowflakes are an example of water molecules self-assembling. Another famous and ubiquitous self-assembling molecule is called deoxyribonucleic acid—better known as DNA!

In your cells, a DNA sequence contains the instructions for building a specific protein that results in a specific trait—say, brown eyes—which is why it’s often referred to as the “genetic code.” DNA works just like a program you might write for a computer, but instead of the binary code of zeroes and ones that most computers use, DNA encodes data using four elements—called nucleotides, or simply bases—represented by the letters A, C, T and G. Each DNA “program” might be hundreds or even thousands of letters long. In principle, we could encode any kind of information by constructing a DNA strand with the letters in a certain order. DNA has even been called “the ultimate data-storage solution” because of its ability to store large amounts of data in a very small space—imagine all of Facebook’s data contained in half a poppy seed!

But what makes DNA even more special is its unique ability to self-assemble according to a simple base-pairing rule: A bonds with T and C bonds with G. Because of this pairing rule, DNA forms a double helix in which the two strands are complementary sequences (Fig. 1). For example, if one strand has the sequence ….CAT….,  the complementary strand would read ….GTA…. In your cells, this property of DNA is the key to its ability to replicate, or make identical copies of itself during cell division, since each strand of the DNA double helix can act as a template for the construction of a complementary strand to form two new complete DNA molecules.

Scientists have developed a number of methods to control self-assembly (see, for example, From Nanowaffles to Nanostructures! by Axel Enders). Using a technique called DNA origami, we can exploit the self-assembly of DNA to create fun and functional shapes from smiley faces (Fig. 2) to superconducting nanowires to cancer-killing nanorobots. Specifically, we assemble DNA strands with the bases in a particular order so their complementary sequences will stick together and fold the strand. By programming the order of bases in a DNA sequence, we can create a certain pattern of folds (Fig. 3). In this way, it is possible to create nearly any shape—cubes, prisms, and more!

Recently, researchers took this idea a step further, using DNA to create unique shapes that act as cages for nanoparticles, forming a so-called voxel. Similar to the voxels used to build worlds in Minecraft, these voxels also act as building blocks that can be assembled into a variety of larger structures (Figs. 4 and 5). The only rule guiding the formation of these structures is that complementary DNA strands pair together, so the shape and size of the lattice depend only on the DNA sequence of the cage and NOT on the nanostructures inside the cage.  These novel self-assembled nanomaterials can be used for targeted drug delivery to specific tissues in the body, building speedier smartphones, and nudging difficult chemical reactions along.

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