Related Experiment Video
Updated: Sep 14, 2025
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High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
Published on: March 3, 2015
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Screening Methods for NMD Inhibitors or Readthrough Activators
Selma Nedjma1, Fabrice Lejeune2
1University of Lille, CNRS, Inserm, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France.
Methods in Molecular Biology (Clifton, N.J.)
|July 23, 2025
Summary
Researchers developed screening methods to find molecules that can fix genetic diseases caused by nonsense mutations. These molecules either enable full protein production or allow partially functional truncated proteins to be made.
Area of Science:
- Genetics
- Molecular Biology
- Drug Discovery
Background:
- Nonsense mutations account for about 10% of genetic diseases.
- These mutations lead to premature stop codons, resulting in non-functional proteins.
- Current strategies aim to restore protein expression or function.
Purpose of the Study:
- To describe methods for screening molecules that can correct nonsense mutations.
- To identify compounds that either inhibit nonsense-mediated mRNA decay (NMD) or promote readthrough of premature termination codons.
Main Methods:
- Development of screening assays to identify modulators of NMD.
- Development of screening assays to identify readthrough-inducing compounds.
- High-throughput screening methodologies.
Main Results:
- Established methods for identifying molecules with therapeutic potential for nonsense mutations.
- Demonstrated the feasibility of screening for compounds targeting two distinct molecular mechanisms.
Conclusions:
- The described methods provide a pathway for discovering novel therapeutics for genetic diseases caused by nonsense mutations.
- Targeting NMD or readthrough offers distinct strategies for rescuing gene expression and protein function.
