Nanotechnology enables the design and fabrication of molecular structures of nanoscale dimensions that hold a great potential for several applications in the near future, including biomedicine. A convenient way to make such nanostructures is to employ synthetic DNA as the building material. These days we can design and synthetize DNA strands that, by simple and predictable interactions, bind to each other just like Lego bricks, and form beautiful 2D and 3D geometries in a very controllable and precise fashion. To date, many nanoscale shapes have been created using DNA bricks, ranging from nanoboxes to more complex geometries, such as a nanoscale Monalisa. To allow potential applications of these nanostructures, however, it would be extremely important to design them so that their assembly and disassembly could be guided by molecular cues of clinical relevance.
In this paper we respond to this need by demonstrating that it is possible to recruit biomarkers, and more specifically antibodies, as molecular builders to build or dismantle DNA nanostructures.
The function of antibodies in our body is to recognize and bind to a specific target (i.e. the antigen), which is often a foreign molecule or protein. For this reason, antibodies are ideal biomarkers because they are produced by our body to target foreign molecules in our blood. Each antibody has its own target and therefore does its job in a highly specific and precise way. This project started a couple of years ago when we realized that this amazing functionality of antibodies (recognize and bind to a specific molecule) could be repurposed for nanotech applications. We had the idea of utilizing antibodies as molecular workers to build nanoscale structures. To do this, we employed DNA bricks that bind to each other and form nanostructures of tubular shape. We then re-engineered such bricks with recognition tags (antigens) so that their assembly is initiated by a specific antibody. The nanotube structure can thus only assemble when the antibody is present in the sample!
Antibodies are highly specialized workers, there are thousands of distinct antibodies in our body each recognizing its own antigen. We took advantage of this amazing feature and designed different bricks each assembling only in the presence of a specific antibody. We also took a step further and engineered our DNA bricks so that not only they assemble into the desired nanostructure in the presence of a specific antibody, but they can also be completely dismantled by a second antibody worker.
This strategy demonstrates the possibility to design intelligent nanostructures that can be built and dismantled in the presence of a specific biomarker. This could have potential applications in the biomedical field, either in diagnostics or therapeutics.