How can space explorers be shielded from cosmic radiation without using massive lead enclosures? Some researchers propose leveraging the unique properties of a protein found in tardigrades that can protect DNA, but the solution is more complex.

Corey Nislow and his team at the University of British Columbia have identified a protein named Dsup (short for Damage Suppressor) that not only protects against radiation but also against various mutagenic substances. However, this protection comes with trade-offs, such as diminished cell viability.

“All the benefits we observe come at a cost,” Nislow states.

Tardigrades, often called water bears, are known for their incredible survival abilities, thriving under extreme conditions such as high radiation, harsh temperatures, desiccation, and even the vacuum of space. In 2016, Dsup was discovered as a critical component of this resilience. When human cells were genetically modified to express Dsup, they displayed enhanced radiation resistance without any adverse effects.

This led to the hypothesis that Dsup could serve as a protective agent against harmful radiation and mutagens. One potential method involves administering the mRNA that encodes Dsup, encapsulated in lipid nanoparticles (LNPs), similar to the technology utilized in mRNA coronavirus vaccines.

“A couple of years ago, I was fully convinced that delivering Dsup mRNA through LNPs to space crews would be highly effective; it wouldn’t alter their genomes but would serve as an efficient countermeasure against DNA damage,” Nislow mentions.

However, ongoing research involving genetically engineered yeast cells producing Dsup has revealed that high concentrations can be toxic, while lower levels can inhibit growth.

Dsup seems to safeguard DNA by physically enveloping it, which, in turn, complicates access for proteins necessary for RNA synthesis and DNA replication before cellular division. It also poses challenges for DNA repair proteins attempting to mend the DNA, particularly in cells with limited repair capabilities, where significant repairs may not occur.

Nislow speculates that Dsup could be beneficial for protecting astronauts, animals, and plants, but emphasizes the importance of controlling its expression levels to optimize its protective effects.

“I completely concur,” says James Byrne, from the University of Iowa, who is studying whether Dsup can shield healthy cells during cancer radiation therapy.

Byrne notes the potential risks associated with continuous Dsup production in all human cells but suggests that temporary expression during periods of need could be advantageous.

“It is undeniable that exceeding a certain threshold can render Dsup toxic,” he acknowledges. Simon Glass from the University of Montpellier also observes that low levels of Dsup can extend the lifespan of nematodes by providing oxidative stress protection, indicating that our understanding of Dsup’s mechanisms remains incomplete.

Jessica Tyler from Weill Cornell Medicine has also engineered yeast to produce Dsup, noting that lower levels than those examined by Nislow appeared beneficial without compromising growth.

“Thus, I disagree with the assertion that Dsup’s protective benefits come at a significant cost,” Tyler affirms, while agreeing on the necessity for regulated Dsup expression.

Although current technologies do not allow for the introduction of the ideal cells to produce Dsup at desired levels, Nislow expresses optimism about future advancements. “There is significant investment and interest in developing effective delivery systems,” he remarks. “This is a challenge that many in the pharmaceutical industry are eager to tackle.”