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- Incorporating base modifications such as pseudouridine reduces innate immune sensing and increases mRNA translation and persistence.
- Rigorous purification to remove dsRNA contaminants prevents innate activation and improves tolerability and expression.
- Engineering the 5' cap and chemically or topologically modified poly(A) tail enhances translation and resists deadenylation.
- Optimized 3′ UTR, inner cap-initiated translation, and circular RNA architectures prolong mRNA stability.
- Delivery systems and host factors such as LNPs, TRIM25, PKR, and ZCCHC14/PAPD5/7 modulate expression and stability.
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