DNA nanotechnology gets real

In the beginning there was the cube. Nadrian Seeman and coworkers at New York University set out in the early 1990s to construct a nanometre scale cube from DNA. The idea was to use the highly sophisticated methods of molecular biology to build DNA into something new and entirely artificial. Linking DNA fragments together by means of hybridisation of overlapping ends followed by ligation, Seeman's group could create a DNA object that definitely had the topology of a cube, even though a high-resolution structure of it wasn't available at the time. Other geometric shapes followed in an endeavour that at that stage still appeared a playful variation on the theme of molecular biology. More than a decade later, Paul Rothemund from CalTech introduced a different approach, which today is a widely used standard and known as DNA origami. Rather than ligating fragments, this approach relies on hybridisation of ready-made parts alone. Typically the core structure of the object to be constructed is defined by one large strand of DNA (the scaffold strand), designed by specialised algorithms to ensure that it folds into the desired shape. This shape is held together by hybridisation with shorter DNA strands, known as staple strands. Rothemund's original demonstration of the origami technique produced two-dimensional patterns on a flat support, such as nanoscale smileys. However, the approach was soon expanded to the production of three-dimensional objects and functional entities. Recent years have brought reports of DNA walkers, assembly lines, cranes, and more. Simultaneously, the use of DNA aptamers — DNA sequences selected for their antibody-like molecular recognition abilities — also showed great promise, for instance in bio-electronic sensors. Structural insights While transmission electron microscopy (TEM) and atomic force microscopy confirmed that the designed DNA objects generally adopted the anticipated shapes, there was no high-resolution structure of any such object. In order to validate the connection between the in silico design of large DNA objects and the physical shape they actually adopt after self-assembly, the groups of Hendrik Dietz at the Technical University of Munich and Sjors Scheres at the MRC Laboratory of Molecular Biology at Cambridge, UK, designed a complex DNA object, with almost twice the mass of a bacterial ribosome, specifically for the task of structure The researchers set out to solve the structure by cryo-electron microscopy (cryo-EM), which uses averaging of images taken of structural identical copies of the same molecular entity. As the …