Codon-Optimized Nucleic Acid Sequences for Host-Specific Expression Control
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Solution Overview
Problem
Current methods for engineering microbiomes face challenges in precisely introducing new genetic information while avoiding unintended expression in unwanted hosts, due to innate variations and horizontal gene transfer, leading to unpredictable ecological impacts.
Innovation Solution
A computerized method for engineering nucleic acid molecules with coding regions optimized for expression in specific organisms by calculating codon usage bias, selecting regulatory elements, and altering DNA cleaving agent sequences, ensuring precise modulation of gene expression and replication in targeted hosts.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If new genetic information is introduced to the environment through horizontal gene transfer, then genetic diversity and adaptability are improved, but precision of gene expression control and ecological safety deteriorate due to unintended expression in unwanted hosts
Solution Approach 1:
The patent applies local quality by customizing the nucleic acid sequence specifically for the target host organism through codon optimization. The coding region is tailored to match the codon usage bias of the desired host while being incompatible with other organisms, thereby achieving precise spatial control of gene expression in the intended host without unintended expression in other organisms through horizontal gene transfer
Solution Approach 2:
The patent employs parameter changes by modifying codon usage frequency and sequence composition to create host-specific expression. By adjusting the codon bias parameters to match the target organism's tRNA pool and regulatory element characteristics, the invention achieves differentiated expression levels across different host organisms, enabling precise control while maintaining genetic diversity
2Productivity
If codon usage bias is optimized for a specific host organism, then gene expression efficiency is improved, but genetic sequence compatibility with other organisms worsens, limiting horizontal gene transfer
Solution Approach 1:
The patent converts the potential harm of reduced horizontal gene transfer capability into a benefit for precise gene expression control. By deliberately optimizing codon usage for the target host, the invention creates sequence incompatibility with other organisms, which prevents unintended expression and ecological risks while ensuring high expression efficiency in the desired host. This selective incompatibility is the intended beneficial outcome
3Manufacturing precision
If regulatory elements are engineered for specific host organisms, then expression control precision is improved, but system complexity increases due to host-specific optimization requirements
Solution Approach 1:
The patent applies universality by using a standardized computational framework that can be applied across different host organisms. The same codon optimization algorithm and regulatory element engineering approach can be universally applied to any target organism by inputting its specific genomic characteristics, thereby achieving host-specific precision without requiring fundamentally different systems for each organism
4Object-affected harmful factors
If nucleic acid sequences are deoptimized for unwanted hosts, then ecological safety is improved by preventing unintended expression, but gene expression flexibility across multiple hosts deteriorates
Solution Approach 1:
The patent applies segmentation by dividing the target organism population into desired hosts and unwanted hosts, then optimizing the nucleic acid sequence for expression only in the desired segment. Through codon bias matching and host-specific regulatory elements, the invention creates expression compatibility with target organisms while inducing incompatibility with non-target organisms, thereby segmenting the expression phenotype across different host populations
Data Source
AI summary
Computerized methods for engineering a nucleic acid molecule comprising a coding region optimized for expression in a first set of organisms and deoptimized for expression in a second set of organisms are provided.


