DNA Nanostructures: Building Blocks for Science and Medicine

For decades, the DNA molecule was understood as the blueprint of life. Scientists now see DNA in a new light: as a programmable material for construction on the smallest scales. This has led to the field of DNA nanotechnology, which uses the molecule’s physical and chemical properties, not its biological information, to build custom-designed objects and devices. This discipline treats DNA as a raw material to create precise two- and three-dimensional structures, opening possibilities in fields from medicine to electronics.

Why DNA is an Ideal Nanomaterial

DNA’s success as a building block for nanotechnology comes from its chemical and structural properties. The primary property is the principle of Watson-Crick base pairing, where the four chemical bases—adenine (A), guanine (G), cytosine (C), and thymine (T)—form specific pairs. A always binds with T, and C always binds with G. This predictable pairing allows complementary strands of DNA to find and bind with high accuracy.

This specific binding drives self-assembly, where individual DNA strands spontaneously form a stable, double-stranded helix. Scientists harness this by designing custom DNA sequences. By programming the sequence of bases, they can dictate how different strands interact and fold, guiding them into predetermined shapes and turning DNA strands into smart building blocks.

Another advantage of DNA is its biocompatibility and biodegradability. As a natural component of living systems, DNA is not harmful to cells or tissues. Over time, it can be broken down and recycled by the body’s natural enzymes. This prevents the long-term accumulation of foreign materials, a desirable feature for applications like drug delivery.

Techniques for Constructing DNA Nanostructures

Several techniques create complex DNA nanostructures, with DNA origami being one of the most prominent. This method uses a long, single strand of DNA, often from a viral genome, as a scaffold. The scaffold is folded into a desired shape by hundreds of shorter DNA strands, known as staple strands. Each staple strand binds to specific regions of the scaffold, pulling them together to hold the structure in its programmed form.

The design process for these structures relies on computational tools. Scientists use software to create a 3D model of the target shape and generate the precise sequences for the staple strands. The software maps the scaffold’s folding path, and the staples act as clips to hold it in place. Once designed, the DNA strands are synthesized, mixed in a solution, and self-assemble as the mixture is heated and then cooled.

Another method is tile-based assembly, which uses smaller, rigid DNA motifs called “tiles.” These tiles are created from a few synthetic DNA strands and designed with “sticky ends,” which are short, single-stranded overhangs. When mixed, the complementary sticky ends cause the tiles to interlock in a repeating pattern, much like ceramic tiles. This forms larger arrays and lattices.

The Diverse World of DNA Nanoforms

DNA nanostructures range from simple two-dimensional patterns to complex three-dimensional objects. In 2D, researchers have assembled flat shapes like squares, triangles, and stars, as well as intricate patterns like smiley faces and nanoscale maps. These flat structures can serve as molecular “breadboards” or canvases for organizing other molecules with high precision.

The jump to three dimensions has produced a wide array of nanoforms. Scientists have constructed polyhedra, including cubes and tetrahedrons, as well as intricate shapes like gears and hollow spheres. Some 3D structures are designed as containers with lids that can be opened and closed, creating tiny boxes for molecular cargo. Nanotubes, which are long, hollow cylinders, have also been assembled for potential use as channels or wires.

Dynamic nanostructures have been developed that can move and perform tasks. These “nanomachines” can be triggered by stimuli like the introduction of another DNA strand or a change in pH. Examples include “DNA walkers,” which are molecular robots that move along a predefined track. Another example is tweezers that can be opened and closed to grasp or release other molecules.

Applications of DNA Nanostructures in Science and Medicine

A promising application for DNA nanostructures is in medicine, particularly for targeted drug delivery. These structures can be designed as containers to encapsulate potent drugs. The containers can be decorated with molecules that recognize and bind to specific cell types, like cancer cells. This allows the payload to be delivered directly to the target while minimizing damage to healthy tissue.

In diagnostics, DNA nanostructures are used to create sensitive biosensors. A rigid DNA structure can serve as a scaffold to hold sensor components in a specific arrangement. This precise organization can amplify signals, allowing for the detection of low concentrations of disease markers or pathogens. For instance, aptamers—short DNA sequences that bind to specific targets—can be attached to a DNA scaffold to detect these markers.

Beyond biology, these structures are tools in materials science and nanoelectronics. They can function as templates to organize other nanoparticles, like gold or silver, into precise patterns. This “nanocasting” process allows for creating custom-shaped metallic nanoparticles. It also enables the arrangement of components for future nano-circuits with high precision.

DNA’s information-coding ability is also used for molecular computing. Interactions between DNA strands can be programmed to perform simple logical operations, similar to those in a computer. By designing systems where specific DNA inputs trigger predictable reactions, scientists are developing biological computing devices. These could one day operate within living cells to diagnose or treat diseases.