Icosahedral nano-shell designed to trap virus particles

An interdisciplinary research team at the Technical University of Munich (TUM) has developed an efficient strategy against most viral infections: they engulf and destroy viruses using DNA origami nano-capsules. In cell cultures, the approach has already been tried against hepatitis and adeno-associated viruses. It may also be effective against corona viruses.

Even before the new coronavirus variety halted the world, Hendrik Dietz, Professor of Biomolecular Nanotechnology at the Physics Department of the Technical University of Munich, and his colleagues were working on the creation of virus-sized particles that self-assemble.

Donald Caspar, a biologist, and Aaron Klug, a biophysicist, established the mathematical rules that govern the formation of viral protein envelopes in 1962. Based on these geometric specifications, the team led by Hendrik Dietz at the Technical University of Munich, with assistance from Seth Fraden and Michael Hagan from Brandeis University in the United States, developed a concept that enabled the creation of artificial hollow bodies the size of viruses.

Cryo-electron microscopic images of nano-half shells made from DNA © Christian Sigl / DietzLab / TUM

In the summer of 2019, the researchers wondered if such hollow bodies may potentially be utilized as a type of “viral trap.” They should be able to bind viruses tightly and therefore remove them out of circulation if they are lined on the inside with virus-binding molecules. However, the hollow bodies must also have enough big holes for viruses to enter the shells.

The researchers opted to construct the hollow bodies for the viral trap using three-dimensional, triangular plates based on the basic geometric shape of the icosahedron. The edges of the DNA plates must be slightly beveled in order for them to combine into bigger geometrical shapes. The proper selection and placement of binding points on the edges ensures that the panels self-assemble to the required 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 Hendrik 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.”

The team’s scientists can construct not just closed hollow spheres, but also spheres with holes or half-shells by changing the binding sites on the edges of the triangles. These can then be employed to capture viruses. The virus traps were tested on adeno-associated viruses and hepatitis B virus cores in collaboration with Prof. Ulrike Protzer’s team, head of the Institute for Virology at TUM and director of the Institute for Virology at the Helmholtz Zentrum München.

Cryo-EM 3D reconstruction of an open nano-shell © Christian Sigl / DietzLab / TUM

“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 complete blocking.” The next step is to test the building blocks on living mice.

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If the idea of simply mechanically eliminating viruses can be realized, this would be widely applicable and thus an important breakthrough, especially for newly emerging viruses. 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 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.”

Programmable icosahedral shell system for virus trapping, Christian Sigl, Elena M. Willner, Wouter Engelen, Jessica A. Kretzmann, Ken Sachenbacher, Anna Liedl, Fenna Kolbe, Florian Wilsch, S. Ali Aghvami, Ulrike Protzer, Michael F. Hagan, Seth Fraden & Hendrik Dietz

Published: April 2021
DOI: https://doi.org/10.1038/s41563-021-01020-4

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