S Protein mRNA UTR Composition for Variant-Stable Vaccine Expression
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing mRNA vaccines face challenges in translation efficiency and stability, particularly against SARS-COV-2 variants like Delta and Omicron, leading to reduced efficacy and increased transmissibility and disease severity.
Innovation Solution
Designing a novel mRNA vaccine with optimized 5′-UTR and 3′-UTR sequences, along with optional polyA, to enhance translation efficiency and stability, enabling cross-protection against SARS-COV-2 wild-type, Delta, and Omicron variants.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing mRNA vaccines are used, then initial protection against SARS-COV-2 is achieved, but translation efficiency and stability are insufficient against variants like Delta and Omicron
Solution Approach 1:
The patent applies parameter changes by optimizing the 5'-UTR and 3'-UTR sequences of the mRNA vaccine to improve translation efficiency and stability. Specifically, the 5'-UTR is designed with a length of 50-200 nucleotides and the 3'-UTR with 100-500 nucleotides, with specific sequence compositions that enhance protein expression and vaccine efficacy against SARS-COV-2 variants.
Solution Approach 2:
The patent applies local quality by designing specific functional elements at different regions of the mRNA molecule. The 5'-UTR contains specific sequences (including potential hairpin structures) that control translation initiation, while the 3'-UTR contains sequences that control translation termination and mRNA stability. Each region is optimized independently for its specific function to achieve overall improved vaccine performance.
2Productivity
If mRNA sequences are optimized for translation efficiency, then protein expression is improved, but mRNA stability and resistance to degradation are reduced
Solution Approach 1:
The patent applies parameter changes by carefully controlling the length and sequence composition of both 5'-UTR and 3'-UTR. The 5'-UTR is set to 50-200 nucleotides and the 3'-UTR to 100-500 nucleotides, with specific GC content and secondary structure characteristics that balance translation efficiency with mRNA stability and resistance to enzymatic degradation.
Solution Approach 2:
The patent applies composite materials by combining multiple functional elements within the UTR sequences. The 5'-UTR may contain hairpin structures, stem-loop motifs, and specific codon usage patterns, while the 3'-UTR contains polyadenylation signals, stem-loop structures, and other stability-enhancing motifs. This composite design achieves both high protein expression and mRNA stability.
3Reliability
If traditional vaccine development methods are used, then existing vaccines are produced, but development time is long and cannot keep pace with viral mutations
Solution Approach 1:
The patent applies preliminary action by designing a universal mRNA vaccine platform with optimized 5'-UTR and 3'-UTR sequences that can be rapidly adapted to different SARS-COV-2 variants. The core mRNA structure serves as a stable platform that can be quickly reconfigured by changing only the coding region to target new variants, eliminating the need to redesign the entire vaccine from scratch.
Solution Approach 2:
The patent applies universality by creating a multi-functional mRNA vaccine design where the optimized 5'-UTR and 3'-UTR provide consistent translational control and stability across different viral variants. This universal platform can be used to produce vaccines against multiple SARS-COV-2 variants by simply changing the coding sequence, enabling rapid response to emerging mutations.
4Productivity
If mRNA vaccines are designed with high translation efficiency, then immune response is enhanced, but mRNA degradation by host enzymes increases
Solution Approach 1:
The patent applies parameter changes by optimizing the sequence composition and structural parameters of the 5'-UTR and 3'-UTR to enhance mRNA stability. Specific sequence motifs, GC content, and secondary structures are designed to reduce recognition and degradation by host enzymes while maintaining high translation efficiency for robust immune response.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The novel mRNA vaccine demonstrates superior immune effects and rapid development capabilities, providing broad protection against multiple strains and facilitating large-scale production.
Implementation Method 1
mRNA is translated in the ribosome to produce specific proteins, thereby exerting biological effects
Implementation Method 2
The 5′-cap structure is crucial for the recognition of the ribosome and the protection of mRNA molecules from RNase
Implementation Method 3
The poly A tail is a long adenine nucleotide sequence, which facilitates the export from the cell nucleus and translation and protects mRNA from degradation
Data Source
AI summary
The present invention relates to an RNA encoding the S protein of SARS-COV-2, a vaccine comprising the RNA, and uses thereof. The present invention also relates to a universal polynucleotide molecule comprising a 5′-UTR and/or a 3′-UTR, and a nucleic acid sequence encoding a protein and/or polypeptide of interest, and optionally comprising a polyA.