Patients undergoing radiation therapy experience debilitating side effects because of toxicity arising from radiation-induced DNA strand breaks in normal peritumoral cells.
Currently, there are limited methods to protect cancer patients from radiation damage. A few drugs can help reduce this damage. For prostate cancer patients, a hydrogel can be used to create a protective barrier between the prostate and the rectum during radiation treatment.
Researchers at MIT, Brigham and Women’s Hospital, and the University of Iowa took inspiration from Tardigrade, a tiny organism that can withstand vast amounts of radiation. They developed a new method to protect patients from radiation damage.
When researchers injected a special RNA into mice, it produced a protein that protected the mice’s cells from radiation damage. If this method can be adapted for humans, it could help many cancer patients tolerate radiation therapy better.
Researchers have been developing new ways to prevent radiation damage for several years. In a new study, they were inspired by the incredible survival ability of tardigrades. These tiny organisms, often found in water, are known for their resilience to extreme conditions. They’ve even been sent to space, where they survived extreme dehydration and cosmic radiation.
Study reveals how tardigrades can endure radiation levels
A key component of tardigrades’ defense systems is a unique protein called Dsup. This protein binds to DNA and helps protect it from radiation damage, allowing tardigrades to survive radiation doses much higher than humans can tolerate.
The researchers thought delivering messenger RNA encoding Dsup to cancer patients’ tissues before radiation treatment might help. This mRNA would make cells temporarily produce the protein, protecting DNA during the treatment. After a few hours, the mRNA and protein would disappear.
To make this work, the researchers needed a way to deliver mRNA that would produce a lot of protein in the target tissues. They tested particles containing polymers and lipids, which have been effective separately for mRNA delivery. They found one particle that best delivered mRNA to the colon and another to mouth tissue.
Ameya Kirtane, an instructor in medicine at Harvard Medical School and a visiting scientist at MIT’s Koch Institute for Integrative Cancer Research, said, “We thought combining polymers and lipids might give us the best results for RNA delivery, and that’s what happened. One advantage of using messenger RNA is that it temporarily makes the protein safer than DNA, which could be incorporated into the cell’s genome.”
“After showing that the particles could successfully deliver mRNA to cells in the lab, the researchers tested this approach in mice to see if it could protect tissue from radiation.”
They injected the particles into mice’s cheeks or rectums a few hours before giving them a radiation dose similar to that received by cancer patients. The researchers saw a 50 percent reduction in radiation-caused DNA damage.
Ben Ho Park, director of the Vanderbilt-Ingram Cancer Center, said the study shows great promise by using natural protection mechanisms to guard healthy cells during radiation therapy for cancer.
The researchers also found that the Dsup protein’s protective effect stayed only at the injection site, which is important to avoid protecting the tumor. They plan to develop a version of the Dsup protein that won’t provoke an immune response for potential use in humans.
If developed for humans, this protein could also protect against DNA damage from chemotherapy and help prevent radiation damage in astronauts.
Journal Reference:
- Kirtane, A.R., Bi, J., Rajesh, N.U. et al. Radioprotection of healthy tissue via nanoparticle-delivered mRNA encoding for a damage-suppressor protein found in tardigrades. Nat. Biomed. Eng (2025). DOI: 10.1038/s41551-025-01360-5
