Synonymous Codon Substitution for Viral Attenuation
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Solution Overview
Problem
Current vaccine design strategies for viruses are largely empirical and inefficient, requiring significant time and resources, and are limited by the need for precise codon composition matching across different cell types and hosts, which is often unknown or variable.
Innovation Solution
Development of nucleic acid molecules with codons substituted to synonymous codons that affect translation rates, optimizing or deoptimizing expression in specific cellular contexts to create modified viruses or vaccine compositions that induce a protective immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If codon deoptimization is used to attenuate viral replication for vaccine design, then vaccine safety is improved, but the complexity of matching codon composition across different cell types and hosts increases
Solution Approach 1:
The patent changes the parameter of codon usage by substituting codons with synonymous codons that have different translation rates. This allows control of viral replication through translation rate modulation rather than through complex codon composition matching across different hosts, simplifying the vaccine design process while maintaining safety through attenuated replication
Solution Approach 2:
The patent segments the viral genome into individual coding sequences that can be independently optimized with specific codon substitutions. Each coding sequence can be tailored with appropriate synonymous codons to achieve desired translation rates in specific cellular contexts, allowing modular and systematic vaccine design
2Adaptability or versatility
If empirical vaccine design strategies are used, then existing vaccine development approaches are maintained, but time and resource investment increase significantly
Solution Approach 1:
The patent performs preliminary computational design of codon-substituted coding sequences before actual vaccine production. By using in-silico methods to predict and optimize translation rates through codon substitution, the approach eliminates much of the empirical trial-and-error process, significantly reducing development time while maintaining compatibility with existing vaccine platforms
3Productivity
If codon composition is optimized for specific cell types or hosts, then translation efficiency is improved, but the precision of reference codon composition knowledge is limited
Solution Approach 1:
The patent applies partial codon substitution rather than attempting to perfectly match codon composition for each specific cell type or host. By substituting only certain codons with synonymous codons to achieve moderate translation rate changes, the approach achieves sufficient translation efficiency improvement without requiring precise knowledge of reference codon composition for every possible cellular context
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
This approach allows for the creation of optimized or attenuated viruses that can be used in vaccines, potentially reducing the complexity of codon composition matching and improving vaccine design efficiency by controlling translation rates, thereby enhancing immune response induction.
Implementation Method 1
a nucleic acid molecule comprising a coding sequence, the coding sequence comprises at least one codon substituted to a synonymous codon, the synonymous codon has a parameter that effects translation rate which differs from the parameter of the at least one codon
Data Source
AI summary
Nucleic acid molecules comprising a coding sequence with at least one codon substituted to a synonymous codon, a modified form of a virus comprising the nucleic acid molecules of the invention, and methods for producing these nucleic acid molecules, and viruses, are provided.