Giving astronauts tardigrade toughness will be harder than we hoped

How can we protect space explorers from cosmic radiation without encasing spaceships in massive layers of lead? Some have suggested dosing them with the DNA-protecting protein from tardigrades – but it’s not going to be that easy.

Corey Nislow and his colleagues at the University of British Columbia in Vancouver have shown that a tardigrade-produced protein called Dsup, short for damage suppressor, can protect against an even wider range of mutation-inducing chemicals than we knew, in addition to radiation. But it also has a trade-off: it reduces the fitness of cells and can even kill them.

“There’s a cost for every benefit that we’ve seen,” says Nislow.

Tardigrades are tiny animals famed for their ability to survive stresses, including being exposed to extreme temperatures, dried out, blasted with radiation, and even exposed to the vacuum of space. In 2016, it was shown that Dsup is one of the keys to their toughness. When human cells were genetically engineered to produce Dsup, they became more resistant to radiation without any reported downsides.

This led to the idea that people could be protected against radiation and mutagenic chemicals by giving them Dsup. One way to do this would be inject them with Dsup-encoding mRNAs encased in lipid nanoparticles (LNPs) – the same technology used in the mRNA covid vaccines.

“Two to three years ago, I was fully on board with the idea that, let’s deliver Dsup mRNA in an LNP to crew members on space missions and you won’t have modified their genomes, but you will have delivered to them a very effective DNA damage countermeasure,” says Nislow.

But his team has now carried out extensive studies of yeast cells modified to produce Dsup. They found that very high levels were fatal, and even lower levels impaired the growth of cells.

Dsup appears to protect DNA by physically surrounding it, says Nislow, but this also makes it harder for proteins to access DNA to make RNA or to replicate the DNA before cell division. It is also harder for DNA repair proteins to access DNA – the team found that in cells with low levels of repair proteins, Dsup could be fatal, likely because crucial repairs didn’t take place.

It may be possible to use Dsup to protect space-travelling people, animals and plants, says Nislow, but it will be crucial to ensure that Dsup in produced only in the cells where it is needed and at the right levels.

“I completely agree,” says James Byrne at the University of Iowa, whose team is looking at whether Dsup can help protect healthy cells during radiation therapy for cancer.

If Dsup were continuously produced in all cells in the human body, it would likely have a significant cost to health, says Byne, but if it is produced only temporarily when needed, it may be beneficial.

“It is absolutely true that above a certain dose, Dsup can have toxic effects,” says Simon Galas at the University of Montpellier in France. However, his team has shown that low levels of the protein can extend the lifespan of nematode worms by protecting them against oxidative stress. Much remains to be discovered about how Dsup works, he says.

Jessica Tyler at Weill Cornell Medicine in New York state has also modified yeast to produce Dsup. At lower levels than those tested by Nislow, it seemed to have beneficial effects with no effect on growth, she says.

“So I do not agree that the protection provided by Dsup comes at a significant cost,” says Tyler. But she does agree that ensuring Dsup is produced at the right levels is crucial.

Getting the right cells in the body to produce the right levels of Dsup cannot be done with existing technology, but Nislow is confident that it will become possible. “There’s so much money and attention on delivery systems,” he says. “It’s a problem that so many people in pharma are motivated to solve.”