The corona pandemic and the SARS-CoV-2 virus are just one example of the fact that in most cases there is no antidote to virus infections. And vaccinations do not always offer complete protection either. In contrast to bacteria, against which antibiotics are generally used for therapy, medicine is usually powerless when it comes to viruses. Researcher of the Technical University of Munich (TUM), Helmholtz Center Munich and the Brandeis University (USA) have now developed a method with which virus infections could be cured in the future.
This “virus trap” is based on the findings of the biologist Donald Caspar and the biophysicist Aaron Klug, who discovered in 1962 the geometrical principles according to which the protein envelopes of viruses are built. Later, Hendrik Dietz, Professor of Biomolecular Nanotechnology at the Physics Department of the Technical University of Munich, and his team, with the support of Seth Fraden and Michael Hagan from Brandeis University in the USA, developed a way of producing artificial hollow bodies the size of a virus.
A few months before the outbreak of the corona pandemic, in summer 2019, the team came up with the idea of the “virus trap”. If nanocapsules made of DNA – the material our genetic material is made of – were to be lined with virus-binding molecules, they should enclose viruses and thus render them harmless. Of course, these hollow bodies would have to have sufficiently large openings so that the viruses can also get inside.
“None of the objects that we had built using DNA origami technology to date would have been able to safely enclose an entire virus – they were simply too small,” says Hendrik Dietz in retrospect. “Building stable hollow bodies of this size was a huge challenge.”
Virus trap based on the modular principle
The team finally decided to base their “trap” on an icosahedron, an object made up of 20 triangular surfaces, and built the hollow bodies for the virus trap from three-dimensional, triangular plates. The edges were beveled a little so that the DNA plates can be put together to form larger geometrical structures. The right choice and positioning of binding points on the edges would then ensure that the panels assemble themselves into the desired objects, explains Dietz.
“In this way, we can now program the shape and size of the desired objects using the exact shape of the triangular plates,” says the scientist. “We can now produce objects with up to 180 subunits and achieve yields of up to 95 percent. The way there was, however, quite rocky, with many iterations. “
80 percent blocking
By varying the binding points at the edges of the triangles, closed hollow spheres can be produced as well as spheres with openings or half-shells, which can then also be used as virus traps. The researchers tested the virus traps together with the team of Prof. Ulrike Protzer, head of the Institute for Virology at TUM and director of the Institute for Virology at the Helmholtz Center in Munich, on adeno-associated viruses and hepatitis B virus cores.
“Even a simple half-shell of the right size shows a measurable reduction in virus activity,” says Hendrik Dietz. “If we put five binding sites for the virus on the inside, for example suitable antibodies, we can already block the virus by 80 percent, if we incorporate more, we achieve a complete block.”
In order to prevent the body fluids, the DNA particles from breaking down again, the finished building blocks were irradiated with UV light and treated on the outside with polyethylene glycol and oligolysine. The particles then remained stable in mouse serum for 24 hours.
Universal construction principle
The next step is now to test the building blocks on living mice, says Dietz. “We are very confident that this material is also well tolerated by the human body.” Prof. Ulrike Protzer explains that bacteria have a metabolism, which is why they can be attacked in different ways. “Viruses, on the other hand, do not have their own metabolism, so antiviral drugs are almost always directed against a specific enzyme in a single virus. Such a development takes time. If the idea of simply mechanically eliminating viruses can be realized, this would be broadly applicable and thus an important breakthrough, especially for newly emerging viruses. “
According to the researchers, the manufacturing costs for the virus traps are biotechnologically justifiable in mass production. “In addition to the proposed application as a virus trap, our programmable system also offers other options,” says Hendrik Dietz. “It would also be conceivable to use it as a multivalent antigen carrier for vaccinations, as a DNA or RNA carrier for gene therapy or as a transport vehicle for drugs.”
cover photo: Lined on the inside with virus-binding molecules, nano half-shells made of DNA material bind viruses to themselves and thus render them harmless. Image: Elena-Marie Willner / DietzLab
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