Sunday, February 26, 2023

Origami DNA Traps Could Keep Large Viruses like SARS-CoV-2 or influenza From Infecting Cells

This seems to be a promising new approach of viral entrapment! Put a shell/envelop/casing/cage around the virus!

"... A study published today (January 18) in Cell Reports Physical Science details how researchers used DNA origami to engineer strands of genetic material into Lego-like structures that form a cage around large pathogens. While the study only looked at how effectively the structures bound to viruses in vitro, the traps could one day help clear viruses from the body. ...
Using DNA origami, the team designed 2D triangle-shaped building blocks that snap together, edge to edge, like puzzle pieces. Then, using cryo-electron microscopy (cryoEM), the researchers confirmed that the triangles assembled themselves into cone-shaped, multisided shells. The team then coated the inside of each shell with virus-binding substances such as antibodies. These shells can sandwich themselves together around viruses, encasing a viral particle more than 100 nm in diameter, which could, in theory, cordon the virus off from a potential host cell and prevent infection, though the team didn’t test for clinical outcomes. Importantly, the shells could also be coated with other virus-binding substances. In this case, the researchers used heparan sulfate, a substance that sticks to many viral protein coats. ...
One hurdle in the assembly process was the finding that the shells, assembled in solutions with high salinity, fell apart under physiological conditions, especially when exposed to low salinity. So, to stabilize the assembled cones further, the researchers used UV light to strengthen the bonds between the building blocks, which prevented the shells from degrading at the relatively low salt concentrations found in the body. They also covered the assembled structures with an oligosine polymer-based coating, preventing them from being degraded by nucleases. On the whole, the process was faster and more efficient than existing DNA origami-based virus-capture techniques, which use multiple types of building blocks ..."

From the abstract:
"Virus-enveloping macromolecular shells or tilings can prevent viruses from entering cells. Here, we describe the design and assembly of a cone-shaped DNA origami higher-order assembly that can engulf and tile the surface of pleomorphic virus samples larger than 100 nm. We determine the structures of subunits and of complete cone assemblies using cryoelectron microscopy (cryo-EM) and establish stabilization treatments to enable usage in in vivo conditions. We use the cones exemplarily to engulf influenza A virus particles and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), chikungunya, and Zika virus-like particles. Depending on the relative dimensions of cone to virus particles, multiple virus particles may be trapped per single cone, and multiple cones can also tile and adapt to the surface of aspherical virus particles. The cone assemblies form with high yields, require little purification, and are amenable for mass production, which is a key requirement for future real-world uses including as a potential antiviral agent."

“Origami” DNA Traps Could Keep Large Viruses From Infecting Cells | The Scientist Magazine® By engineering structures out of DNA, scientists could potentially prevent larger viruses, like coronaviruses and influenza viruses, from interacting with cells.


Graphical abstract


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