TREMs Read Through Premature Termination Codons
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Solution Overview
Problem
Current methods for modulating protein synthesis and addressing premature termination codons in endogenous open reading frames are inefficient, particularly in treating diseases associated with such codons.
Innovation Solution
Development of modified tRNA-based effector molecules (TREMs) with non-naturally occurring modifications that can support protein synthesis, introduce amino acids into peptide chains, and pair with premature termination codons to modulate protein expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If current methods are used to modulate protein synthesis, then the process is simple, but the efficiency is low particularly in treating diseases associated with premature termination codons
Solution Approach 1:
The patent applies parameter changes by introducing non-naturally occurring modifications to tRNA molecules, specifically altering the nucleotide composition and structure to create TREMs that can efficiently recognize and read through premature termination codons. These modifications include changing base pairing properties and stability parameters of the tRNA molecule to enhance its function in modulating protein synthesis efficiency.
Solution Approach 2:
The invention uses composite materials by combining natural tRNA structural elements with non-naturally occurring modified nucleotides and sequences. This creates a hybrid effector molecule (TREM) that integrates both natural recognition capabilities and enhanced functional properties, resulting in a composite molecular structure that achieves high efficiency in treating diseases associated with premature termination codons.
2Reliability
If modified tRNA-based effector molecules with non-naturally occurring modifications are used, then protein expression is enhanced, but the molecular complexity increases
Solution Approach 1:
The patent applies local quality by introducing non-naturally occurring modifications at specific, localized positions within the tRNA molecule rather than uniformly throughout. These targeted modifications at particular nucleotide positions enhance stability and function in specific regions critical for protein synthesis and PTC recognition, while maintaining the overall natural structure and function of the tRNA molecule.
Solution Approach 2:
The invention uses parameter changes by systematically modifying specific properties of the tRNA molecule including nucleotide composition, base pairing characteristics, and structural stability parameters. These controlled changes in molecular parameters enhance the reliability and stability of the protein synthesis process while enabling the TREM to effectively recognize and read through premature termination codons.
3Productivity
If TREMs are used to introduce amino acids into peptide chains, then protein synthesis is supported, but the number of modifications required increases
Solution Approach 1:
The patent applies the taking out principle by extracting and isolating the essential functional elements required for amino acid incorporation and PTC recognition. Rather than requiring numerous modifications throughout the molecule, the invention identifies and implements only the critical modifications needed in key functional regions, thereby supporting protein synthesis efficiency with a minimized number of non-naturally occurring modifications.
Solution Approach 2:
The invention uses partial action by implementing modifications only in the specific regions of the tRNA molecule that are critical for amino acid incorporation and PTC recognition, rather than modifying the entire molecule. This targeted approach supports productive protein synthesis and amino acid incorporation while minimizing the total quantity of non-naturally occurring modifications required.
Data Source
AI summary
The invention relates generally to tRNA-based effector molecules having a non-naturally occurring modification and methods relating thereto.