Engineered 5′ UTR Nucleic Acid Constructs for Stable mRNA Expression
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Solution Overview
Problem
Existing mRNA vaccines face challenges in efficiently regulating the expression of target genes, which is crucial for effective vaccine performance.
Innovation Solution
The development of a nucleic acid construct comprising engineered 5' untranslated regions (UTRs) derived from genes like ARHGAP15, which can regulate the expression of target genes in mRNA vaccines.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If existing mRNA vaccines use conventional UTR structures, then the basic function of mRNA translation is maintained, but the expression efficiency and stability of target genes are insufficient
Solution Approach 1:
The patent applies parameter changes by modifying the nucleotide sequences of 5'UTR and 3'UTR regions in mRNA vaccines. Specifically, it uses engineered 5'UTR sequences (such as those from ARHGAP15, HSPB1, HBB, or CCL13 genes) and optimized 3'UTR sequences to change the translational and stability parameters of mRNA, thereby simultaneously improving expression efficiency and stability of target genes
Solution Approach 2:
The patent employs composite materials by combining engineered 5'UTR elements with optimized 3'UTR elements and poly(A) tail structures in a single mRNA construct. This composite approach integrates multiple functional components (cap structure, 5'UTR, ORF, 3'UTR, poly(A) tail) where each component is specifically designed to contribute to both translation efficiency and mRNA stability, resolving the contradiction between productivity and reliability
Data Source
AI summary
The present disclosure relates to a nucleic acid construct and use thereof. Specifically, the present disclosure relates to a nucleic acid construct comprising an engineered UTR, and use thereof in the prevention and treatment of a disease (for example, prevention of virus infection). The UTR can significantly improve the expression efficiency of a target gene in the nucleic acid construct.