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Updated: Jul 1, 2025

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
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The AsiDNA™ decoy mimicking DSBs protects the normal tissue from radiation toxicity through a

Anouk Sesink1,2, Margaux Becerra1,2, Jia-Ling Ruan3

  • 1Institut Curie, Université PSL, CNRS UMR3347, INSERM U1021, 91405 Orsay, France.

NAR Cancer
|March 13, 2024
PubMed

Insights

AsiDNA™ protects normal cells from radiation damage by inducing a cell cycle arrest, improving survival after radiotherapy. This novel drug shows radioprotective effects in both preclinical models and normal cells.

Area of Science:

  • Oncology
  • Radiation Biology
  • Molecular Biology

Background:

  • AsiDNA™ is a DNA damage response decoy designed to enhance cancer treatment efficacy.
  • Previous studies confirmed AsiDNA™'s safety and tolerability when combined with radio- and chemotherapy.
  • The potential radioprotective role of AsiDNA™ in normal tissues warranted further investigation.

Purpose of the Study:

  • To investigate the radioprotective effects of AsiDNA™ in normal cells and tissues.
  • To elucidate the molecular mechanisms underlying AsiDNA™-mediated radioprotection.
  • To evaluate AsiDNA™'s efficacy in preclinical models of radiation toxicity.

Main Methods:

  • In vitro studies using normal epithelial cells and fibroblasts to assess AsiDNA™'s effect on cell cycle and survival post-irradiation.
  • In vivo studies in mouse models evaluating AsiDNA™'s impact on radiation-induced lung fibrosis and intestinal crypt survival.
  • Ex vivo analysis using precision cut lung slices to confirm mechanistic findings.

Main Results:

  • AsiDNA™ induced a p53/p21-dependent G1/S cell cycle arrest in normal cells, enhancing their survival after irradiation.
  • This effect was absent in tumor cells, preserving AsiDNA™'s radiosensitizing properties.
  • In vivo studies demonstrated reduced lung fibrosis and increased intestinal crypt survival in mice treated with AsiDNA™ and radiotherapy.
  • Similar protective effects were observed with FLASH radiotherapy, with or without AsiDNA™.

Conclusions:

  • AsiDNA™ exhibits significant radioprotective properties in normal tissues.
  • The mechanism involves a p53-dependent G1/S arrest in healthy cells, distinct from its action in tumor cells.
  • AsiDNA™ holds promise for mitigating radiation toxicity in patients undergoing radiotherapy.

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