A tardigrade protein helped reduce radiation damage in mice

A protein found in tardigrades — tiny animals less than a millimeter long — can protect mice from radiation damage.

Most cancer patients undergo radiation therapy as part of their treatment, often leading to devastatingly painful side effects. But there may be hope for mitigating some of that damage. Mice with cells engineered to produce a protective protein unique to tardigrades experienced reduced radiation damage, researchers report February 26 in Nature Biomedical Engineering.

Radiation attacks the DNA of tumor cells, preventing tumor growth and eventually killing it. But it also damages the DNA of healthy tissue near the tumors, destroying those cells, too. People undergoing treatment for head and neck cancer can develop damaged throats or mouths, making eating and drinking extremely painful. Prostate cancer patients may experience rectal bleeding.

“I treat cancer patients with radiation, and I see a lot of side effects from treatment itself — side effects that can be really debilitating and severe,” says James Byrne, a radiation oncologist at the University of Iowa in Iowa City.

These unintended consequences can lead people to stop treatment before their tumors are under control. While at MIT, Byrne and biomedical researcher Giovanni Traverso had “started to explore possibilities of creating radiation protection,” Byrne says, when they realized they could use a little help from tardigrades. 

Tardigrades may be as tiny as dust mites, but they are tough little creatures — even capable of tolerating extreme conditions like outer space. Nicknamed “water bears,” they can survive radiation doses about 1,000 times the lethal dose to humans.

Tardigrades produce a key damage-suppressor protein known as Dsup, which binds to their DNA to protect them from radiation. Byrne and Traverso wanted to somehow arm mice with this protein so they would be better equipped to deal with radiation.

The duo and their colleagues used lipid nanoparticles — tiny particles composed of fat molecules that can carry chemicals — to deliver messenger RNA, or mRNA, with instructions for creating the Dsup protein directly into mouse cheek and rectum cells. Byrne and his colleagues discovered that when exposed to radiation, the DNA of mice producing Dsup proteins showed fewer signs of radiation-induced damage compared to the DNA of mice that couldn’t make Dsup.

“It highlights some of the value of research into areas where one might not immediately see a clinical outcome, like studies of DNA damage in tardigrades,” says Zachary Morris, an oncologist at the University of Wisconsin-Madison who was not involved with the study. “You can take findings from more basic or fundamental science and pair them with new delivery mechanisms and suddenly be in a situation where you have a very impactful finding with immediate relevance to human health.”

The researchers now plan to carefully evaluate the safety of this system before testing it on humans. Since tardigrade mRNA is foreign to humans, they want to ensure that injecting it doesn’t lead to adverse reactions. Instead of directly injecting cells as they did with mice, they also want to develop patient-friendly ways to deliver the mRNA to human cells, such as using hydrogels.

“We were hoping to use what nature has really perfected as [this] optimized radiation protection, to potentially help patient care in the long term,” Byrne says.