biostudies-literatureLi SCongressionally Directed Medical Research ProgramsNHLBI NIH HHSNational Heart Lung and Blood InstituteUS Army Medical Research and Development CommandCancer Prevention and Research Institute of Texas330-347https://www.ebi.ac.uk/biostudies/studies/S-EPMC12857769biostudies-literatureUnknown34(1)Radiation therapy, while effective against cancer, often causes collateral damage to surrounding healthy tissues, leading to DNA damage that can precipitate genomic instability and cancer. Despite the enormity of the problem, there is currently no FDA-approved agent to prevent or treat skin damage caused by ionizing radiation. In this study, ionizing radiation-induced dose-dependent genomic and mitochondrial DNA damage, leading to apoptosis in primary cutaneous cells. Prior treatment with mRNA encoding telomerase reverse transcriptase (TERT) substantially reduced radiation-induced DNA damage in human primary skin cells and tissues. Mechanistically, TERT mRNA pretreatment enhances DNA repair through the homologous recombination pathway, reduces mitochondrial ROS, and decreases apoptosis without extending telomere length during the experimental period, suggesting a non-canonical function of TERT to accelerate cellular recovery from radiation. These findings highlight a potential therapeutic approach for preventing radiation-induced skin injury.Molecular therapy : the journal of the American Society of Gene TherapyTelomerase mRNA therapy protects human skin against radiation-induced DNA damage.PMC12857769R01 HL1483381R01HL133254R01 HL133254MB2300261R01HL148338RP200619Spiegel AJFriedman JDCarrier JShah VVBrannan KWMorales EOlmsted-Davis ECourt KANguyen TKCLi SGodin BMojiri ARahimi MChang DFCooke JPTiwari ALudlow ATfalseTelomerase mRNA therapy protects human skin against radiation-induced DNA damage.Radiation therapy, while effective against cancer, often causes collateral damage to surrounding healthy tissues, leading to DNA damage that can precipitate genomic instability and cancer. Despite the enormity of the problem, there is currently no FDA-approved agent to prevent or treat skin damage caused by ionizing radiation. In this study, ionizing radiation-induced dose-dependent genomic and mitochondrial DNA damage, leading to apoptosis in primary cutaneous cells. Prior treatment with mRNA encoding telomerase reverse transcriptase (TERT) substantially reduced radiation-induced DNA damage in human primary skin cells and tissues. Mechanistically, TERT mRNA pretreatment enhances DNA repair through the homologous recombination pathway, reduces mitochondrial ROS, and decreases apoptosis without extending telomere length during the experimental period, suggesting a non-canonical function of TERT to accelerate cellular recovery from radiation. These findings highlight a potential therapeutic approach for preventing radiation-induced skin injury.2026-01-01T00:00:00Z2026 Jan2026-06-13T05:23:40.509Z2026-06-13T03:08:42.555ZS-EPMC128577694095841510.1016/j.ymthe.2025.09.029