UTR Sequence Design for Intracellular mRNA Stability and Biosynthesis
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Solution Overview
Problem
mRNA has lower structural stability than DNA, limiting its industrial application and biosynthetic efficiency in fields like mRNA vaccines, necessitating improved intracellular stability and biosynthesis.
Innovation Solution
Incorporation of specific UTR sequences with high homology to SEQ ID NO: 1 to SEQ ID NO: 37, which stabilize nucleic acids and enhance mRNA biosynthesis, used in vectors, transfectants, immunity-boosting compositions, and pharmaceutical compositions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If mRNA is used for direct protein expression in cytoplasm, then transient expression efficiency is improved, but structural stability deteriorates
Solution Approach 1:
The patent divides the mRNA molecule into functional segments, specifically identifying and optimizing the 5' UTR and 3' UTR regions separately from the coding sequence. This segmentation allows independent optimization of stability elements in UTR regions without affecting the protein-coding capacity, thereby resolving the contradiction between transient expression efficiency and structural stability.
Solution Approach 2:
The patent applies local quality by introducing specific sequence motifs and structural elements only in the UTR regions (5' UTR and 3' UTR) while keeping the coding sequence intact. This localized modification approach enhances overall mRNA stability through specific local features such as secondary structures and sequence compositions without altering the global function of protein expression.
2Device complexity
If conventional mRNA sequences are used, then simplicity is maintained, but intracellular stability and biosynthetic efficiency deteriorate
Solution Approach 1:
The patent changes specific parameters of the mRNA sequence including nucleotide composition, GC content, secondary structure formation, and presence of specific motifs in the 5' UTR and 3' UTR regions. These parameter modifications are made within the UTR sequences to enhance intracellular stability and biosynthetic efficiency while maintaining the overall simplicity of the mRNA construct design.
3Duration of action of stationary object
If UTR sequences are optimized for stability, then mRNA half-life is improved, but manufacturing complexity increases
Solution Approach 1:
The patent performs preliminary design and selection of optimal UTR sequences with desired stability properties before the actual mRNA synthesis process. By pre-characterizing and selecting UTR sequences that provide enhanced stability, the manufacturing process itself remains relatively simple, as the stability enhancement is achieved through sequence selection rather than complex post-synthesis modifications.
Data Source
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AI summary
Unlike DNA, mRNA has the advantage of enabling transient expression of a desired protein directly in the cytoplasm without having to enter the nucleus, and thus, attempts to use mRNA vaccines are actively underway. However, mRNA has lower structural stability than DNA, and thus has limitations in industrial application. Therefore, the present invention relates to a UTR sequence that improves the intracellular stability and biosynthesis of mRNA, and a composition for stabilizing nucleic acids, comprising the UTR sequence. The UTR sequence of the present invention has excellent effects of stabilizing nucleic acids and promoting the expression of a target protein, and thus is expected to be greatly used in the health/medical field.