In an international collaboration involving the University of Twente and universities in Finland and Australia, researchers have succeeded in reprogramming the capsids of plant viruses into different shapes. They did this by folding nanoscale DNA structures into moulds around which the capsids form. They have published the results of their research in the scientific journal Nature Nanotechnology.
For medicines to be transported efficiently through the body, they need to be suitably packaged. Capsids potentially offer a solution, but their shape is mainly determined by the genetic properties of the virus. Researchers are therefore trying to develop techniques to control the shape and size of these nano-packages to make them suitable for transport through the body.
The researchers in this project used ‘DNA origami’ structures. These structures are tiny, only tens to hundreds of nanometres in size, and made entirely of DNA. By folding the DNA into precisely the right shape, the researchers can build a template to which the viral proteins can attach. “It’s really just like folding paper origami to build intricate 3D structures. Only here we do it with very rigid DNA”, explains Jeroen Cornelissen.
The viral proteins were actually much more flexible than they expected. “We managed to build various structures with the capsids, including straight tubes, but also a donut shape. The latter is an entirely different shape to the normal spherical structure of capsids”, says Cornelissen. It is a simple but very effective strategy for changing the shape of virus proteins.
The researchers used cryogenic electron microscopy to precisely determine the formation of the nanostructures, even to the level of the individual molecules. They were able to measure minuscule changes at a temperature of around -200°C. This is the first time that these highly structured proteins have been imaged using this technique.
The researchers see a lot of potential in the technology. “Our approach is flexible, and not limited to a single type of protein; we have so far tested it on proteins from four different viruses. Moreover, we can adapt the templates for a variety of applications, for example by incorporating RNA into the origami. Useful or site-specific proteins can be attached to the RNA to create even more complex shapes and properties”, explains Aalto University professor Mauri Kostiainen.
This joint research project was carried out at Aalto University (Finland), with researchers from the University of Helsinki (Finland), Griffith University (Australia), Tampere University (Finland) and the University of Twente (the Netherlands). “It is the result of years of collaboration between our university and Prof. Kostiainen’s research group”, says Cornelissen.
Prof. Jeroen Cornelissen is affiliated with the Molecules & Materials cluster of the Biomolecular Nanotechnology department (MolMat; Faculty of Science and Technology/MESA+). The research entitled ‘DNA-origami-directed virus capsid polymorphism’ was published in the scientific journal Nature Nanotechnology.