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ACE mRNA (Additional Chimeric Element incorporated IVT mRNA) for Enhancing Protein Expression by Modulating
Sora Son1, Minsa Park1, Jin Kim1
1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Gyeongsangnam-do, 52828, Republic of Korea.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|March 6, 2024
Summary
A novel Additional Chimeric Element incorporated mRNA (ACE mRNA) reduces immune responses and enhances protein expression without costly modified nucleotides. This breakthrough advances mRNA therapeutics and vaccines by improving safety and efficacy.
Area of Science:
- Biotechnology
- Molecular Biology
- Immunology
Background:
- In vitro transcribed messenger RNA (IVT mRNA) therapeutics face challenges with immunogenicity, leading to reduced efficacy.
- Current methods to reduce immunogenicity involve expensive chemically modified nucleotides, posing cost and safety concerns.
Purpose of the Study:
- To introduce a novel mRNA structure, Additional Chimeric Element incorporated mRNA (ACE mRNA), to mitigate immunogenicity without modified nucleotides.
- To evaluate the immunomodulatory and protein expression capabilities of ACE mRNA.
Main Methods:
- Development of ACE mRNA, featuring a conventional IVT mRNA segment and an RNA/DNA chimeric segment.
- Assessment of ACE mRNA's immunogenicity by measuring its ability to restrict RIG-I and STING-mediated immune activation.
- Evaluation of protein expression efficiency of ACE mRNA compared to conventional IVT mRNA.
Main Results:
- ACE mRNA significantly reduced the immunogenicity of unmodified IVT mRNA.
- ACE mRNA demonstrated enhanced protein expression efficiency.
- The RNA/DNA chimeric elements in ACE mRNA were shown to restrict RIG-I and STING immune pathways.
Conclusions:
- ACE mRNA offers a promising strategy to modulate IVT mRNA immunogenicity without requiring chemically modified nucleotides.
- This approach enhances the safety and efficacy of mRNA-based therapeutics and vaccines.
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