Engineered mRNA 5'UTR Design for Consistent Protein Expression
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Solution Overview
Problem
Inconsistent protein expression levels following in vitro transcribed mRNA (IVT mRNA) delivery in vivo necessitate the development of highly efficient 5' untranslated regions (5'UTRs) to enhance mRNA expression efficiency.
Innovation Solution
Engineered mRNA comprising specific 5'UTR sequences, 3'UTR sequences, and an open reading frame (ORF), optimized for protein production, are encapsulated in vectors and delivered via lipid nanoparticles, ensuring synergistic enhancement of protein expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional IVT mRNA is used, then production flexibility and cost-effectiveness are improved, but protein expression levels in vivo are inconsistent and insufficient
Solution Approach 1:
The patent applies parameter changes by optimizing the 5'UTR sequence parameters including GC content (40-60%), length (30-70 nucleotides), and specific sequence composition to enhance ribosome binding efficiency. This systematic parameter optimization resolves the contradiction by making protein expression levels both higher and more consistent across different mRNA products while maintaining the flexibility of the IVT platform
2Productivity
If the 5'UTR sequence is optimized for high translation efficiency, then protein production increases, but mRNA structure stability may be compromised
Solution Approach 1:
The patent applies local quality by creating specific functional zones within the 5'UTR: a stable structural core region (with optimized GC content and secondary structure elements) and a ribosome access region (with optimized Kozak sequence and spacing). This local differentiation allows the mRNA to simultaneously achieve structural stability for protection and localized high-efficiency translation initiation
Data Source
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AI summary
Provided are an engineered mRNA and a method for improving protein expression using same. Also provided is the use of such engineered mRNA in gene therapy and/or genetic vaccination.