Tardigrade Protein To Shield Healthy Cells From Radiation

Radiation therapy is one of the primary treatment options for cancer. The high-energy radiation causes DNA breaks in the tissues exposed to it. Cancer cells, which divide rapidly, often cannot repair the damage in time and die as a consequence of the treatment. In contrast, most healthy cells in our body divide much more slowly, and thus have a better chance to successfully repair the damage before their next division.

However, some healthy cells in the body also divide quickly—such as the epithelial cells that line the mucous membranes of the digestive tract. As a result, even highly targeted radiation therapy directed at a tumor can damage healthy epithelial cells as well. This damage can manifest as painful and severe sores that may sometimes force doctors to suspend treatment.

In a new study published in Nature Biomedical Engineering, researchers demonstrated that injecting a protein from tardigrades into the healthy tissue of mice before radiation exposure can significantly reduce tissue damage.

Radiation therapy is one of the primary treatments against cancer. Woman undergoing radiation therapy | Science Photo Library

Increased Resistance

Tardigrades are microscopic creatures renowned for their remarkable resilience and extraordinary ability to survive in extreme environments. They can endure conditions ranging from severe dehydration and freezing cold to scorching heat—and even high levels of radiation. One of the mechanisms that helps them withstand radiation damage is a protein called DSUP (DNA-associating protein). This protein wraps around the DNA molecules in the tardigrades' cells, absorbing radiation and preventing it from damaging their genetic material.

Research teams led by Giovanni Traverso from Broad Institute in Massachusetts and James Byrne of the University of Iowa, investigated whether this protein could also protect mouse and human cells. To test this, the scientists synthesized RNA copies of the gene that encodes for DSUP and packaged them in a fatty envelope—similar to the delivery method used in RNA-based COVID-19 vaccines. This approach, which proved effective during the pandemic, offers a key advantage: it provides only temporary protection, as the RNA molecules naturally degrade within a few days, causing the treatment’s effects to gradually diminish.

In their initial experiment, the researchers cultured human epithelial cells taken from the mouth or rectum, treated them with the engineered RNA, and then exposed the cells to high levels of radiation. The cells that received the RNA—and therefore produced the protective protein—sustained only half as much damage as untreated cells. Accordingly, the survival rate of the treated cells was twice as high.

Tardigrades can survive a wide range of conditions, including severe dehydration, freezing cold, scorching heat, and even high levels of radiation. Scanning electron microscope image of a tardigrade | Steve Gschmeissner / Science Photo Library

Next, the researchers injected the RNA into one cheek of healthy mice, then exposed both cheeks to radiation. Once again, the tissue that received the RNA showed only half as much damage—provided the radiation was administered within 24 hours of the injection. When the radiation was delayed by four days, however, the protective effect dropped to just 25 percent, as expected due to the natural breakdown of RNA over time, preventing protein production.

To determine whether the RNA injection might also protect tumor tissue, the team repeated the experiment—this time with a cancerous tumor in one cheek and RNA injected into the healthy cheek. They found that the RNA did not reach the tumor cells and had no effect on the growth of the malignant tissue. In addition, cell culture experiments showed that the fatty envelope used to deliver the RNA molecules preferentially targeted healthy cells: approximately 90 percent of healthy cells absorbed the RNA, compared to just 15 percent of cancer cells.

The researchers hope that this RNA-based treatment—carrying instructions for  producing the tardigrade protein—could one day help patients better tolerate radiation therapy and experience fewer side effects.

A visual explanation of the experiment and its findings.