Radioprotection of healthy tissue via nanoparticle-delivered mRNA encoding for a damage-suppressor protein found in tardigrades
Patients undergoing radiation therapy experience debilitating side effects because of toxicity arising from radiation-induced DNA strand breaks in normal peritumoural cells. Here, inspired by the ability of tardigrades to resist extreme radiation through the expression of a damage-suppressor protein...
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| Veröffentlicht in: | Nature biomedical engineering Jg. 9; H. 8; S. 1240 |
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| Format: | Journal Article |
| Sprache: | Englisch |
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01.08.2025
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| ISSN: | 2157-846X, 2157-846X |
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| Abstract | Patients undergoing radiation therapy experience debilitating side effects because of toxicity arising from radiation-induced DNA strand breaks in normal peritumoural cells. Here, inspired by the ability of tardigrades to resist extreme radiation through the expression of a damage-suppressor protein that binds to DNA and reduces strand breaks, we show that the local and transient expression of the protein can reduce radiation-induced DNA damage in oral and rectal epithelial tissues (which are commonly affected during radiotherapy for head-and-neck and prostate cancers, respectively). We used ionizable lipid nanoparticles supplemented with biodegradable cationic polymers to enhance the transfection efficiency and delivery of messenger RNA encoding the damage-suppressor protein into buccal and rectal tissues. In mice with orthotopic oral cancer, messenger RNA-based radioprotection of normal tissue preserved the efficacy of radiation therapy. The strategy may be broadly applicable to the protection of healthy tissue from DNA-damaging agents. |
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| AbstractList | Patients undergoing radiation therapy experience debilitating side effects because of toxicity arising from radiation-induced DNA strand breaks in normal peritumoural cells. Here, inspired by the ability of tardigrades to resist extreme radiation through the expression of a damage-suppressor protein that binds to DNA and reduces strand breaks, we show that the local and transient expression of the protein can reduce radiation-induced DNA damage in oral and rectal epithelial tissues (which are commonly affected during radiotherapy for head-and-neck and prostate cancers, respectively). We used ionizable lipid nanoparticles supplemented with biodegradable cationic polymers to enhance the transfection efficiency and delivery of messenger RNA encoding the damage-suppressor protein into buccal and rectal tissues. In mice with orthotopic oral cancer, messenger RNA-based radioprotection of normal tissue preserved the efficacy of radiation therapy. The strategy may be broadly applicable to the protection of healthy tissue from DNA-damaging agents. Patients undergoing radiation therapy experience debilitating side effects because of toxicity arising from radiation-induced DNA strand breaks in normal peritumoural cells. Here, inspired by the ability of tardigrades to resist extreme radiation through the expression of a damage-suppressor protein that binds to DNA and reduces strand breaks, we show that the local and transient expression of the protein can reduce radiation-induced DNA damage in oral and rectal epithelial tissues (which are commonly affected during radiotherapy for head-and-neck and prostate cancers, respectively). We used ionizable lipid nanoparticles supplemented with biodegradable cationic polymers to enhance the transfection efficiency and delivery of messenger RNA encoding the damage-suppressor protein into buccal and rectal tissues. In mice with orthotopic oral cancer, messenger RNA-based radioprotection of normal tissue preserved the efficacy of radiation therapy. The strategy may be broadly applicable to the protection of healthy tissue from DNA-damaging agents.Patients undergoing radiation therapy experience debilitating side effects because of toxicity arising from radiation-induced DNA strand breaks in normal peritumoural cells. Here, inspired by the ability of tardigrades to resist extreme radiation through the expression of a damage-suppressor protein that binds to DNA and reduces strand breaks, we show that the local and transient expression of the protein can reduce radiation-induced DNA damage in oral and rectal epithelial tissues (which are commonly affected during radiotherapy for head-and-neck and prostate cancers, respectively). We used ionizable lipid nanoparticles supplemented with biodegradable cationic polymers to enhance the transfection efficiency and delivery of messenger RNA encoding the damage-suppressor protein into buccal and rectal tissues. In mice with orthotopic oral cancer, messenger RNA-based radioprotection of normal tissue preserved the efficacy of radiation therapy. The strategy may be broadly applicable to the protection of healthy tissue from DNA-damaging agents. |
| Author | Traverso, Giovanni Witt, Emily McGovern, Megan K Machado, Nicole Howard, Michelle E Kim, Hyunjoon Kim, Nayoon Bi, Jianling Hong, Theodore S Manchkanti, Srija Rajesh, Netra U Kirtane, Ameya R Venkatachalam, Veena Freitas, Dylan Hatfield, Samual J Huang, Xisha Chan, Alvin Becker, Sarah L Rosenstock, Lauren Byrne, James D Collins, Joy E Jimenez, Miguel Tang, Chaoyang Cafi, Arielle B Lopes, Aaron |
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| SubjectTerms | Animals DNA Damage Humans Male Mice Nanoparticles - chemistry Radiation-Protective Agents RNA, Messenger - administration & dosage RNA, Messenger - genetics RNA, Messenger - metabolism Tardigrada - genetics Tardigrada - metabolism |
| Title | Radioprotection of healthy tissue via nanoparticle-delivered mRNA encoding for a damage-suppressor protein found in tardigrades |
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