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Updated: Nov 1, 2025
10:06
Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
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Risdiplam, the First Approved Small Molecule Splicing Modifier Drug as a Blueprint for Future Transformative
Hasane Ratni1, Renata S Scalco1, Alexander H Stephan1
1pRED, Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland.
ACS Medicinal Chemistry Letters
|June 18, 2021
Summary
Targeting messenger RNA (mRNA) with small molecules, once a challenge, is now a viable therapeutic strategy. The development of splicing modifiers and drugs like risdiplam for spinal muscular atrophy (SMA) proves this innovative approach can treat diseases.
Area of Science:
- Pharmacology
- Molecular Biology
- Drug Discovery
Background:
- Selectively targeting messenger RNA (mRNA) with small molecules was historically a significant scientific hurdle.
- The development of small molecule splicing modifiers has overcome previous limitations in mRNA targeting.
Purpose of the Study:
- To highlight the transformation of mRNA targeting from a scientific curiosity into a viable therapeutic technology.
- To showcase the current state and potential of small molecule mRNA targeting for disease treatment.
Main Methods:
- Leveraging biophysical methods for understanding molecular interactions.
- Employing screening methods for identifying potential drug candidates.
- Developing small molecule splicing modifiers.
Main Results:
- Proof of concept for small molecule mRNA targeting established through drug development (e.g., risdiplam for spinal muscular atrophy).
- Demonstration of a viable technology platform for targeting diseases at the mRNA level.
Conclusions:
- Small molecule mRNA targeting is a proven and evolving therapeutic modality.
- Current approaches, supported by advanced methods, are poised to deliver new drugs with significant therapeutic impact.
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