So far, there are no effective and widely applicable antidotes against most virus infections – not even against the Sars-Cov-2 coronavirus. But now researchers have developed a new strategy for combating viruses: virus traps made from DNA. Their nanocapsules, made from genetic material using the method of DNA origami, can bind viruses and thus render them harmless. In initial tests, these virus traps were able to almost completely neutralize hepatitis viruses and adeno-associated viruses in nutrient solutions and cell cultures. If this is also confirmed in animal experiments, such DNA virus traps would be a versatile weapon against viral pathogens.
There are antibiotics against dangerous bacteria – medicine, on the other hand, is almost powerless against many virus infections. This is also demonstrated by the current corona pandemic: drugs such as remdesivir or dexamethasone can alleviate or shorten severe courses of Covid-19 somewhat. But so far the infection cannot really be stopped by these means. Antibody preparations, on the other hand, have the potential to effectively support the immune system against Sars-CoV-2 or other viral pathogens, but they are highly specific and very expensive. So far, the only effective protection against Covid-19 has been vaccinations, but these cannot be developed equally quickly and easily for all viruses – for some diseases caused by viruses there are still neither cures nor vaccines.
DNA as a building material
Christian Sigl from the Technical University of Munich and his colleagues have now developed a new approach against viruses. The starting point for this was the discovery made decades ago that our genetic material DNA is ideally suited for producing robust and versatile nanoconstructs. The binding behavior of the DNA building blocks enables them to organize themselves. In the method of DNA origami, DNA strands are made to self-organize into the desired structures through targeted modification. Sigl and his colleagues therefore wondered whether such DNA constructs could not also be used to construct biomechanical virus traps. If it were to be lined with virus-binding molecules on the inside, it could bind viruses tightly to itself and thus pull them out of circulation.
To do this, however, the team first had to produce hollow DNA bodies that had sufficiently large openings for the viruses. “None of the objects that we had built using DNA origami technology to date would have been able to safely contain an entire virus – they were simply too small,” explains Sigl’s colleague Hendrik Dietz. “Building stable hollow bodies of this size was a huge challenge.” However, after a few tests, the researchers found a way of creating icosahedra of different sizes from DNA. These hollow spheres, consisting of 20 triangular surfaces, are shaped similarly to the capsids of many viruses and are made up of triangles made from DNA struts. By varying the binding points on the edges of the triangles, Sigl and his team can not only create closed hollow spheres, but also spheres with openings or half-shells. These can then be used as virus traps.
Tests with hepatitis and adeno-associated viruses successful
The research team then examined how well these DNA constructs function as virus traps in several tests with adeno-associated viruses (AAV) and hepatitis B viruses (HBV). To do this, they added DNA half-shells to nutrient solutions or cell cultures with these viruses and watched what happened. So that the DNA constructs in the body fluids are not immediately broken down, the team previously irradiated them with UV light and treated them with polyethylene glycol and oligolysine. As a result, the particles remained stable in mouse serum for 24 hours. The neutralization tests showed: “Even a simple half-shell of the right size shows a measurable reduction in virus activity,” reports 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.”
According to the researchers, the DNA virus traps offer a new way of rendering viruses harmless and thus fighting infections. The main advantage of the DNA constructs is that they can be easily adapted to different viruses. “If the idea of simply mechanically eliminating viruses can be realized, it would be broadly applicable and thus an important breakthrough, especially for newly emerging viruses,” says co-author Ulrike Protzer from the German Center for Infection Research in Munich. Another advantage: The starting materials for the virus traps can be mass-produced biotechnologically at a reasonable cost. Next, the scientists want to test their virus traps on living mice and other animals. “We are very confident that this material will also be well tolerated by the human body,” says Dietz.
Source: Christian Sigl (Technical University of Munich) et al., Nature Materials, doi: 10.1038 / s41563-021-01020-4