A new method to create artificial viruses could help solve the challenge of delivering new generations of drugs into diseased cells, for instance via gene therapy, according to a new Dutch study.
Traditional pharmaceuticals are made up of relatively small molecules that typically end up – without too much trouble – in the diseased tissues and cells where they are needed. The newest types of drugs being developed, on the other hand, consist of large biomolecules, for instance proteins and genetic material such as DNA and RNA. Although these modern drugs have huge potential in terms of their effects, they have proved challenging to deliver into cells. DNA, for example, is inherently incapable of penetrating cells and is quickly broken down.
Breaking and entering
This is where viruses come into play. Viruses are experts at ‘breaking into’ cells, where they deliver their own DNA or RNA. That’s how viruses survive, spreading infection into people, animals or plants.
Scientists have previously used natural viruses – after making them harmless – to deliver drugs into cells. However, the process of rendering natural viruses harmless is a tricky business that has yet to be perfected, often causing unintended side effects. Researchers are therefore looking into developing alternative, synthetic viruses.
In the new study, reported in the journal Nature Nanotechnology, scientists from four Dutch universities managed to mimic the crucial tricks that viruses use to wrap their genetic material into a neat ‘package’ that can get into cells.
Solving a 30-year-old puzzle
Key to the feat was understanding exactly how viruses self-assemble. And the basis for this understanding was a theoretical model that explains how the RNA of the tobacco mosaic virus assemble a protective coat of proteins – a question that had remained unexplained for the last 30 years.
Paul van der Schoot from the Technical University of Eindhoven (TU/e), who recently developed the model together with Daniela Kraft from Leiden University, added the missing link in the puzzle.
This missing link is called allosteric regulation, a phenomenon that enables proteins to help each other to bond to RNA. “It’s difficult for the first protein to bond,” explains Van der Schoot in a TU/e press release. “But the first helps the second, and the second helps the third, and so on.”
Creating new opportunities with synthetic coat proteins
Using this knowledge and the natural machinery of yeast cells, the researchers were able to produce artificial viral coat proteins. When these ‘packaging proteins’ are mixed with DNA, they spontaneously form a strong, protective protein coat around each DNA molecule, producing ‘synthetic viruses’.
The researchers expect that the high degree of precision with which the proteins ‘package’ the DNA molecules will offer many opportunities for mimicking other smart features of viruses. The technique could lead to safe and effective ways to deliver new-generation medicines in the future, especially within the emerging field of gene therapy.