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Updated: Nov 14, 2025
Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes
Published on: May 23, 2025
Integrative network analyses of transcriptomics data reveal potential drug targets for acute radiation syndrome
Robert Moore1, Bhanwar Lal Puniya1, Robert Powers2
1Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE, USA.
Abstract:
Recent political unrest has highlighted the importance of understanding the short- and long-term effects of gamma-radiation exposure on human health and survivability. In this regard, effective treatment for acute radiation syndrome (ARS) is a necessity in cases of nuclear disasters. Here, we propose 20 therapeutic targets for ARS identified using a systematic approach that integrates gene coexpression networks obtained under radiation treatment in humans and mice, drug databases, disease-gene association, radiation-induced differential gene expression, and literature mining. By selecting gene targets with existing drugs, we identified potential candidates for drug repurposing. Eight of these genes (BRD4, NFKBIA, CDKN1A, TFPI, MMP9, CBR1, ZAP70, IDH3B) were confirmed through literature to have shown radioprotective effect upon perturbation. This study provided a new perspective for the treatment of ARS using systems-level gene associations integrated with multiple biological information. The identified genes might provide high confidence drug target candidates for potential drug repurposing for ARS.
Insights
This study identifies 20 potential therapeutic targets for acute radiation syndrome (ARS) by integrating multiple data sources. Eight validated targets show radioprotective effects, offering new drug repurposing opportunities for ARS treatment.
Area of Science:
- Radiation biology
- Genomics
- Pharmacology
Background:
- Understanding the health effects of gamma-radiation exposure is critical due to potential nuclear disasters.
- Effective treatments for acute radiation syndrome (ARS) are urgently needed.
Purpose of the Study:
- To identify novel therapeutic targets for ARS.
- To explore drug repurposing opportunities for ARS treatment.
Main Methods:
- Integrated analysis of gene coexpression networks from human and mouse radiation studies.
- Utilized drug databases, disease-gene associations, and literature mining.
- Focused on genes with existing drug associations for repurposing potential.
Main Results:
- Identified 20 potential therapeutic targets for ARS.
- Eight specific genes (BRD4, NFKBIA, CDKN1A, TFPI, MMP9, CBR1, ZAP70, IDH3B) were confirmed to have radioprotective effects.
- Highlighted potential drug candidates for ARS through repurposing.
Conclusions:
- This study offers a systems-level approach to ARS target identification.
- The identified genes represent promising candidates for developing new ARS therapies.
- Drug repurposing of identified targets could accelerate treatment development for ARS.
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