Codon-Optimized Sgp130 Nucleic Acid Sequences for Recombinant Protein Production
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Solution Overview
Problem
The recombinant production of sgp130 is challenging due to low yields and the presence of undesired side products, hindering its application in treating diseases like Crohn's disease and rheumatoid arthritis.
Innovation Solution
Codon optimization of the DNA encoding sgp130 leads to increased protein yields, specifically reducing shorter side products, through the use of optimized nucleic acid sequences that better align with host organism codon usage patterns, enhancing expression in both mammalian and bacterial cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional DNA sequences encoding sgp130 are used for recombinant production, then the production process is simple, but the protein yield is low
Solution Approach 1:
The patent applies parameter changes by optimizing the DNA sequence through codon optimization. The coding sequence is redesigned to match the codon usage preferences of the host organism (mammalian or bacterial cells), changing nucleotide parameters while maintaining the same amino acid sequence. This results in improved translation efficiency and significantly higher protein yields (up to 20-fold in mammalian cells, 3-fold in bacterial cells) without complicating the overall production process
2Manufacturing precision
If conventional DNA sequences are used, then the production process is straightforward, but undesired shorter side products are generated
Solution Approach 1:
The patent uses parameter changes by modifying the DNA sequence parameters through codon optimization. The optimized sequence eliminates cryptic initiation sites and alternative splicing patterns that cause truncated side products. By carefully selecting codons that match host preferences while maintaining proper reading frame and eliminating premature stop codons, the patent achieves higher protein purity with minimal side products
Solution Approach 2:
The patent converts potential harmful elements in the DNA sequence (such as cryptic start sites or alternative reading frames that cause truncated proteins) into beneficial features. Through codon optimization, these potentially problematic sequences are redesigned to either be eliminated or to serve as controlled regulatory elements, transforming what would be sources of impurity into factors that enhance production precision
Data Source
AI summary
Described are codon optimized sgp130 encoding nucleic acid molecules as well as a method for the highly efficient recombinant production of sgp130 in mammalian cells or bacteria using a nucleic acid molecule of the invention.


