Cancer treatment can be absolutely brutal. Over 60% of patients with cancer undergo radiation therapy at some point in their disease process and scientists are looking for ways to make this procedure more bearable. In this quest, they’ve turned to one of nature’s hardiest creatures for inspiration.
Tardigrades — the microscopic animals nicknamed “water bears” — can survive conditions that would annihilate most life. And a new study suggests a protein that helps these creatures endure extreme radiation may be useful for protecting cells during radiation therapy. Researchers found that delivering the tardigrade’s damage-suppressor protein to healthy tissues significantly reduced DNA damage from radiation in mice. This breakthrough might one day make cancer radiotherapy safer and more effective.
The Double-Edged Sword of Radiation Therapy
Radiation has been used to kill cancer cells for over a century, but it remains a double-edged sword. High-energy rays that zap tumors also burn through normal cells, causing painful side effects.
“Radiation can be very helpful for many tumors, but we also recognize that the side effects can be limiting. There’s an unmet need with respect to helping patients mitigate the risk of damaging adjacent tissue,” says Giovanni Traverso, an associate professor of mechanical engineering at MIT and a gastroenterologist at Brigham and Women’s Hospital, and study author.
Over the years, doctors have tried various ways to spare healthy cells from radiation. A few protective drugs can be given to absorb some of the damage, but these drugs can have serious side effects and are rarely tolerated well.
Enter the tardigrade.
These eight-legged micro-animals, often found in moss or water droplets, are famous for their almost absurd resilience. Tardigrades have survived blazing heat and freezing cold, colossal pressures, desiccation, and even the vacuum of outer space. They can withstand radiation doses 1,000 times higher than would kill a human. Despite their cuddly nicknames (“moss piglets” or “water bears”), tardigrades are tough.
Traverso and James Byrne, an assistant professor of radiation oncology at the University of Iowa, were eager to see whether we could harness the superpower of tardigrades to protect against radiation.
Tardigrades vs Radiation
The first key discovery came in 2016: a unique protein in tardigrade cells called Dsup (short for “damage suppressor”) was found to bind to DNA and shield it from radiation injury. Dsup acts like a microscopic bodyguard, protecting DNA from the direct energy of radiation as well as from harmful byproducts that form when radiation hits water in cells. Experiments showed that human cells engineered to produce Dsup suffered far less DNA breakage under X-rays — around 40% less damage.
In the new study, researchers tried to get Dsup into cells with a different mechanism. Instead of genetically engineering cells (a permanent change that would be risky and complicated), the researchers turned to messenger RNA (mRNA) — the same type of temporary genetic instruction used in many vaccines.
Messenger RNA carries the code to produce proteins but only sticks around for a short time. The idea was to inject mRNA for the Dsup protein into healthy tissues right before radiation therapy; the cells would read the mRNA and churn out Dsup protein for a few hours, gaining a brief radiation-resistant state, then the mRNA and Dsup would degrade, and disappear.
“One of the strengths of our approach is that we are using a messenger RNA, which just temporarily expresses the protein, so it’s considered far safer than something like DNA, which may be incorporated into the cells’ genome,” says Kirtane.
Getting mRNA into the right cells is no simple task — mRNA is a fragile molecule that must be packaged to slip into cells without being destroyed. The team engineered special nanoparticles combining lipids (fats) and polymers to ferry the Dsup mRNA into tissues.
“We thought that perhaps by combining these two systems — polymers and lipids — we may be able to get the best of both worlds and get highly potent RNA delivery. And that’s essentially what we saw,” Kirtane says.
It Works (In Mice, So Far)
The approach was promising in lab tests, so researchers moved to living animals. They used mice with a form of oral cancer to simulate the scenario of a human cancer patient. Just as planned, the team injected the Dsup-encoding mRNA nanoparticle into healthy tissue adjacent to the tumor — specifically into the cheek (buccal tissue) for some mice, and into the rectum for others — then a few hours later gave the mice a dose of radiation similar to what human patients receive.
Tissues pre-treated with the tardigrade protein suffered far less DNA damage than untreated tissues. In mice that received the protective mRNA in the rectum, researchers saw about 50% fewer double-strand DNA breaks from the radiation compared to control mice. In the mouth tissue, the effect was even more pronounced — roughly a two-thirds reduction in radiation-induced DNA damage.
Crucially, this protection did not reduce the cost of cancer-fighting efficacy. The tumor cells in these mice were not getting the Dsup mRNA (since the injection was localized to nearby healthy tissue), and the study confirmed that the tumors responded to radiation just as they normally would.
If this strategy translates to humans, it could dramatically improve the cancer treatment experience. Radiation therapy has long been a balancing act: oncologists must deliver a dose high enough to wipe out tumor cells, but not so high that a patient’s healthy organs are irreparably harmed. In practice, the tolerance of normal tissue often dictates the maximum dose, meaning some tumors can’t be blasted as aggressively as doctors would like. Even at safe doses, patients can be left with debilitating side effects — severe mouth pain, digestive issues, skin burns, fatigue — that impact their quality of life. Many are forced to pause treatment to recover, giving the tumor a chance to regroup. A way to fortify healthy cells during radiation could change all of this.
By using the Dsup protein as a temporary shield, doctors might be able to administer full courses of radiation without breaks, and patients could potentially avoid the worst complications. “If developed for use in humans, this approach could benefit many cancer patients,” the researchers say.
Journal Reference: Radioprotection of healthy tissue via nanoparticle-delivered mRNA encoding for a damage-suppressor protein found in tardigrades, Nature Biomedical Engineering (2025). DOI: 10.1038/s41551-025-01360-5
