Scientists create a ‘DNA origami’ to control the assembly of viruses

2023-07-17 17:27:18

Using the mechanisms of viruses to cure ourselves: this is one of the objectives of the new personalized medical treatments. However, there are still many challenges to make these treatments a daily reality. Now, an international group of scientists has just gone a step further: they have been able to create a ‘template’, like a kind of ‘DNA origami’, to control the way in which viruses are assembled. The conclusions have just been published in ‘Nature Nanotechnology‘.

In a very simplified way, viruses are DNA or RNA (genome) encapsulated within a protective shell made of proteins (capsid). Since they do not have mechanisms to replicate, they need to use those of the cell they infect and which provides them with substrate, energy and the necessary machinery. Once attached to them, they release their genome, replicate, and assemble their progeny.

Until now, attempts have been made to modify the DNA of natural human viruses, such as lentiviruses, for treatments in animals; however, management capabilities were limited or had security issues. A second path was then opened: taking advantage of these mechanisms but creating artificial viruses (called artificial viral vectors) to carry genetic information.

Programming DNA to fold

This new method is able to control how viruses are assembled into different shapes, such as origami (the old Japanese technique of creating shapes by folding paper). “We were able to control the shape, size and topology of the virus protein by using user-defined DNA origami nanostructures as binding and assembly platforms, which were embedded within the capsid,” explains Frank Sainsbury, one of from the study authors.

Applicability of the capsid coating on structures of different thickness and shape Springer Nature

Sainsbury also compares it to wrapping a gift: the virus proteins are deposited on these DNA nanostructures that have previously been programmed to take one form or another. “In addition, the protein coatings of the virus could protect the encapsulated DNA origami from degradation.” That is, to serve as a protective layer for the genetic material that it keeps inside and that is the key to future treatments, including new vaccines and drug delivery systems.

“Until now, the tools to control the assembly process in a programmable way were not very efficient,” explains Donna McNeale, also an author of the study. “But what’s more, our approach is also not limited to just one type of virus capsid protein unit and can also be applied to RNA-DNA origami structures.”

The next steps will be to understand how different viruses self-assemble (as not all of them do it in the same way) and how this could be used to encapsulate different payloads. This will allow more virus-like particles (viral vectors) to be designed and modified for a variety of uses.

“With the huge design space that exists between viruses that could be used as carriers, there is still a lot to learn from studying them. We will continue to push the boundaries of how virus-like particles can be assembled and what can be learned from using them as carriers for drugs, vaccines and biochemical reaction vessels,” says Sainsbury.