Nanostructures composed of DNA building blocks can be made to self-assemble and disassemble in response to certain environmental conditions. The new technique has been developed by Francesco Ricci and colleagues at the University of Rome, who engineered the process by attaching specific antigens to the molecules, which could then only bind to specific connecting antibodies. Their research could bring about a variety of new applications in nanomedicine.

DNA molecules are ideal building blocks for nanoscale devices because they are inexpensive and easy to make and have highly-predictable base-pairing mechanisms. By simply binding the molecules together, researchers can construct intricate, origami-like structures that can be microns in size.

Structures that have been built already include the practical – such as cages that can be opened and closed – and the fanciful, including a microscopic copy of the Mona Lisa. A desirable next step for this idea is to create nanostructures that assemble and disassemble themselves in response to certain environmental cues – something that could be particularly useful for medical applications.

Y-shaped proteins

Ricci’s team achieved this using IgG antibodies, which are Y-shaped proteins. As essential components of the immune system, these molecules typically operate by binding to and then immobilizing pathogens. The antibodies respond to certain environmental triggers, including temperature and pH. Thousands of types of IgC antibodies are known to exist, with the tip of each individual Y-prong binding to highly specific groups of molecules associated with particular pathogens, known as antigens. In medical applications, they are critically important as natural biomarkers of diseases.

In their study, Ricci and colleagues achieved synthetic DNA self-assembly for the first time by first attaching specific antigens to the molecules. When the relevant antibodies were released into the solution, each individual Y-prong attached itself to an individual antigen, linking molecules together. This then enabled the blocks to quickly assemble themselves into hollow tubular structures that were up to a few microns in length. Finally, they disassembled themselves when the researchers released a second specific antibody into the solution, which disabled the IgG-antigen bounds.

Since antibodies are produced naturally to target foreign molecules, Ricci’s team believe that IgG antibodies are the ideal agents for building intricate and intelligent nanostructures in highly specific parts of the body. They predict that their technique could have diverse clinical applications, especially for drug delivery and diagnostics. Through further studies, they describe how improvements in the technology could bring about cell-free synthetic biology systems, capable of performing logical functions that mimic those of electronic circuits.

The research is described in Nature Communications.