New Antiviral Approach Uses DNA Origami Method to Create Icosahedral Shell

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Abstract low polygon 3D shape
[Source: gremlin/Getty Images]

Researchers at Technical University of Munich (TUM) have developed a new approach to engulf and neutralize viruses with nano-capsules tailored from genetic material using their
“DNA origami method.” They report that this strategy has already been tested against hepatitis and adeno-associated viruses (AAVs) in cell cultures. They say it may also prove successful against corona viruses.

The team and their collaborators at Brandeis University (USA) are proposing a novel strategy for the treatment of acute viral infections. They have developed nanostructures made of DNA that can trap viruses and render them harmless. Their study is reported in Nature Materials.

This science has a long history. In 1962, the biologist Donald Caspar and the biophysicist Aaron Klug discovered the geometrical principles according to which the protein envelopes of viruses are built. Based on these geometric specifications, the team around Hendrik Dietz at the Technical University of Munich, supported by Seth Fraden and Michael Hagan from Brandeis University in the USA, developed a concept that made it possible to produce artificial hollow bodies the size of a virus.

In the summer of 2019, this team asked whether such hollow bodies could also be used as a kind of “virus trap”. If they were to be lined with virus-binding molecules on the inside, they should be able to bind viruses tightly and thus be able to take them out of circulation. For this, however, the hollow bodies would also have to have sufficiently large openings through which viruses can get into the shells.

“None of the objects that we had built using DNA origami technology at that time would have been able to engulf a whole virus – they were simply too small,” says Dietz. “Building stable hollow bodies of this size was a huge challenge.” Dietz is Professor of Biomolecular Nanotechnology at the Physics Department of the Technical University of Munich, and his team were working on the construction of virus-sized objects that assemble themselves.

Starting from the basic geometric shape of the icosahedron, an object made up of 20 triangular surfaces, the team decided to build the hollow bodies for the virus trap from three-dimensional, triangular plates.  For the DNA plates to assemble into larger geometrical structures, the edges must be slightly beveled. The correct choice and positioning of binding points on the edges ensure that the panels self-assemble to the desired objects.

“In this way, we can now program the shape and size of the desired objects using the exact shape of the triangular plates,” says Dietz. “We can now produce objects with up to 180 subunits and achieve yields of up to 95 percent. The route there was, however, quite rocky, with many iterations.”

By varying the binding points on the edges of the triangles, the team’s scientists can not only create closed hollow spheres, but also spheres with openings or half-shells. These can then be used as virus traps.

The team tested the virus traps 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 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 complete blocking.

The researchers report that the starting materials for the virus traps can be mass-produced biotechnologically at a reasonable cost. “In addition to the proposed application as a virus trap, our programmable system also creates other opportunities,” says 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.”

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