TREMs Modulate tRNA Pools for Rare Codon Translation
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Solution Overview
Problem
Current methods fail to effectively modulate tRNA pools in cells to address contextually-rare codons, which can lead to compromised protein production and associated disorders due to limitations in tRNA availability and abundance.
Innovation Solution
The use of modified tRNA-based effector molecules (TREMs) that pair with specific codons to modulate tRNA pools by increasing the abundance of isoacceptor tRNAs, thereby improving protein synthesis efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional tRNA pools are used, then natural protein synthesis occurs, but protein production is compromised due to contextually-rare codons
Solution Approach 1:
The patent modifies the tRNA pool composition by introducing engineered tRNA molecules with specific anticodons that complement contextually-rare codons. This changes the parameter of tRNA abundance distribution, ensuring adequate pairing capacity for rare codons while maintaining overall protein synthesis reliability and productivity.
2Productivity
If tRNA pool is modulated to address contextually-rare codons, then protein synthesis efficiency improves, but system complexity increases
Solution Approach 1:
The patent applies local quality by specifically targeting and modifying only the tRNA species corresponding to contextually-rare codons, rather than uniformly altering the entire tRNA pool. This localized approach improves protein synthesis efficiency at specific codon positions while minimizing overall system complexity and maintaining compatibility with natural tRNA functions.
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 enhances protein production by ensuring adequate tRNA availability for contextually-rare codons, potentially treating disorders related to tRNA limitations and improving protein expression parameters.
Implementation Method 1
The TREM, TREM core fragment or TREM fragment has an anticodon that pairs with: (a) the codon having the first sequence; or (b) the codon other than the codon having the first sequence
Data Source
AI summary
The disclosure relates generally to uses of tRNA-based effector molecules having a non-naturally occurring modification.