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DNA Origami offers a novel solution to create virus capsids of varied shapes

Monday, 24 July 2023
Researchers from Finland, Australia and the Netherlands utilise the benefits of DNA Origami to modify the shape of virus capsids.

Researchers from universities in Finland, Australia and from University of Twente in Netherlands have succeeded in reprogramming the capsids of plant viruses into different shapes. They achieved this by folding nanoscale DNA structures into moulds around which the capsids take form. The results of their research have been published in the scientific journal Nature Nanotechnology.

In order for medicines to be effectively transferred through the body, they need to be suitably packaged. Capsids offer a solution to this problem but their shape is mostly determined by the genetic properties of the virus. Therefore researchers are trying to develop techniques to modify the shape and size of these nano-packages to make them more suitable for transport throughout the body.

DNA Origami

This problem prompted them to explore ‘DNA origami’ structures. These are very small, only tens to hundreds of nanometers in size, and made entirely of DNA. By folding the DNA into the desired shape, they build a template onto 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 far 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’s a simple yet extremely effective strategy to change the shape of viral proteins.

Cryogenic Electron Microscopy

The researchers used cryogenic electron microscopy to determine the price formation of the nano-structures, to the level of the individual molecules. They were able to capture miniscule changes, even at a temperature of around -200°C. This imaging technique has never been used before on structured proteins!

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).

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.

DOI: 10.1038/s41565-023-01443-x