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mRNA Stability: An Unresolved Challenge for Broad Therapeutic Applications
Yiming Wang1,2,3, Xiaoxue Wang1,2,3, Yuan Lu1,2,3
1Department of Chemical Engineering, Tsinghua University, Beijing, China.
Biotechnology Journal
|October 27, 2025
Summary
Messenger RNA (mRNA) instability hinders its therapeutic use. This review covers strategies like sequence optimization, structural modifications, and delivery systems to enhance mRNA stability for diverse disease treatments.
Area of Science:
- Biotechnology
- Molecular Biology
- Therapeutics
Background:
- Messenger RNA (mRNA) holds significant therapeutic promise for various diseases, including infectious diseases, cancers, and rare conditions.
- The single-stranded nature of mRNA makes it susceptible to enzyme-mediated degradation, posing a major challenge to its clinical application.
- Enhancing mRNA stability is critical for unlocking its full therapeutic potential.
Purpose of the Study:
- To review current strategies for improving mRNA stability.
- To explore methods for mitigating mRNA degradation.
- To discuss the future outlook of mRNA technology in biotechnology.
Main Methods:
- Review of literature on mRNA stabilization techniques.
- Analysis of sequence and structural optimization methods for mRNA.
- Exploration of RNA modifications and novel mRNA structures (e.g., circular mRNA, self-amplifying RNA).
- Discussion of mRNA delivery systems and their role in stability.
Main Results:
- Strategies to enhance mRNA stability include enzyme removal, protective substances, optimized storage, and transport.
- Sequence optimization of 5' UTR, ORF, and 3' UTR, along with RNA modifications, significantly improves stability.
- Novel mRNA structures like circular and self-amplifying RNA offer advanced stabilization approaches.
- Delivery materials also contribute to improved mRNA stability.
Conclusions:
- Optimizing mRNA stability is achievable through various chemical, structural, and delivery-based strategies.
- Continued advancements in mRNA technology are paving the way for its broader application in biotechnology.
- mRNA is poised to become a key player in versatile biotechnological fields.
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