Tardigrade Protein Shields Mouse Cells from Radiation

Tardigrades, or water bears, are microscopic animals with incredible survival skills—they can withstand extreme temperatures and the vacuum of space. They can also tolerate high doses of radiation. Researchers previously discovered that tardigrades can survive more than 1,000 times the lethal dose for humans.¹ So, how do these tiny creatures protect themselves so well?

The answer lies in a damage-suppressing protein (Dsup) that binds to DNA and minimizes harmful strand breaks.² Inspired by tardigrades' remarkable radiation tolerance, researchers explored whether this mechanism could help patients with cancer better tolerate radiation therapy.

To address this, a team of scientists from the Massachusetts Institute of Technology, Brigham and Women’s Hospital, and the University of Iowa packaged Dsup messenger RNA (mRNA) into nanoparticles. After injecting the nanoparticles into mice with oral cancer, the researchers found that tissue cells produced the therapeutic Dsup protein, which reduced radiation-induced damage. Their results, published in Nature Biomedical Engineering, present a promising approach to protect healthy tissue during radiation therapy.³

Radiation can harm surrounding healthy tissue, leading to injury and inflammation, but protective measures remain limited. The researchers hypothesized that delivering the protective tardigrade mRNA to tissues before radiation therapy could prompt cells to temporarily express Dsup, safeguarding DNA during treatment. Within hours, the mRNA and protein would degrade without integrating into the genome.

To optimize mRNA delivery, the team screened libraries of both polymer and lipid components for an effective vehicle. “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,” said Ameya Kirtane, a pharmaceutical scientist at the University of Minnesota and a study coauthor, in a press release.

First, the team tested whether their polymer-lipid nanoparticles could effectively deliver green fluorescent protein (GFP) mRNA to cells by injecting this into the buccal or rectal tissue of mice. They found that protein expression peaked six hours later and was mostly undetectable after 96 hours. The nanoparticles remained localized to the injection site, and both GFP and Dsup-GFP were expressed inside cells.

Next, they evaluated the effects of Dsup-carrying nanoparticles on oral and colonic cell lines after radiation exposure. The team used a marker for double-stranded DNA damage and found that the tardigrade mRNA treatment protected cells against radiation-induced damage.

The team then tested their Dsup delivery system in healthy mice. To maximize protein expression, they injected the treatment into the oral cavity of mice and exposed them to a single radiation dose six hours later. Mice that received Dsup treatment showed a reduction of double-stranded DNA damage. The researchers also checked for unintended systemic effects but found no significant changes in either suppressive or inflammatory cytokine levels.

To study their treatment in a disease model, the researchers introduced oral squamous cell carcinoma cells into one side of a mouse’s cheeks. Once the tumors grew to roughly 50mm³,the researchers then injected Dsup treatment into the opposite cheek before exposing the tumor to radiation. DNA damage measurements showed the same trend seen in healthy mice: Dsup treatment significantly reduced radiation-induced DNA damage while remaining localized near the injection site. Notably, the mRNA treatment also did not influence tumor growth before radiation. This delivery system is proof of concept that a Dsup-based therapy may protect healthy tissues during radiation therapy.

“This is an entirely novel approach for protecting healthy tissue and may eventually offer a way to optimize radiation therapy for patients while minimizing these debilitating side effects,” said James Byrne, a physician-scientist at the University of Iowa and study coauthor, in a press release.

Harnessing the protective powers of this unique tardigrade protein paves the way for future development in treatments to safeguard against DNA damage caused by radiation, chemotherapy drugs, and even space travel.