SARS-CoV-2 Spike Protein Polynucleotide Codon Optimization
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Solution Overview
Problem
There is a need for effective antigens to prevent and treat 2019-nCOV infection, as no vaccine is currently available, and existing information on the epidemiology and clinical features of the virus is scarce, with a requirement for scalable and inexpensive antigen production.
Innovation Solution
Development of polynucleotides encoding the 2019-nCOV spike protein, optimized for expression in host cells, which retain the native protein's conformation and induce neutralizing antibodies, along with vectors, antibodies, and vaccine compositions for immunoprotective responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If polynucleotides are optimized for recombinant expression in host cells, then the level and duration of spike protein expression is increased, but the complexity of polynucleotide design and manufacturing increases
Solution Approach 1:
The patent applies parameter changes by optimizing codon usage frequency to match the host cell's preferred codons, adjusting GC content to optimal ranges, and modifying polynucleotide sequence parameters to enhance expression levels and duration while maintaining manufacturability
Solution Approach 2:
The patent applies local quality by making specific localized modifications to the polynucleotide sequence, such as optimizing individual codons in high-expression regions, adjusting GC content in promoter and coding regions differently, and targeting specific structural elements for optimization without redesigning the entire sequence
2Reliability
If the spike protein conformation is retained to induce neutralizing antibodies, then vaccine efficacy is improved, but the difficulty of producing correctly folded protein increases
Solution Approach 1:
The patent applies intermediary by introducing chaperone proteins or folding assistants that mediate the folding process of the spike protein, helping it achieve and maintain its native conformation during recombinant production without requiring complex post-translational modification systems
Solution Approach 2:
The patent applies copying by creating simplified versions or fragments of the full spike protein (such as receptor-binding domains or stabilized S2 subunits) that can be more easily produced and folded while still retaining the ability to induce neutralizing antibodies
3Productivity
If polynucleotides are optimized for high expression in multiple host cells, then production scalability is improved, but the cost of optimization and validation increases
Solution Approach 1:
The patent applies universality by designing a standardized polynucleotide optimization platform that can be applied across multiple host cell types (e.g., HEK293, CHO, insect cells) using the same codon optimization algorithms and validation protocols, reducing redundant optimization work for each host system
Solution Approach 2:
The patent applies preliminary action by performing in-silico codon optimization, structural modeling, and expression prediction before actual laboratory experimentation, allowing the selection of the most promising polynucleotide sequences to be tested experimentally, thereby reducing the number of costly wet-lab iterations needed
Data Source
AI summary
The present invention relates to Coronavirus 2019-nCOV spike protein, polynucleotides encoding said spike protein, antibodies and vaccines for treatment or prevention of 2019-nCOV infection.