TREMs with Non-Naturally Occurring Modifications
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for modifying tRNAs to enhance protein synthesis and amino acid introduction into peptide chains are limited by the lack of effective non-naturally occurring modifications that can specifically target and modulate tRNA functions without disrupting cellular processes.
Innovation Solution
Development of modified tRNA-based effector molecules (TREMs) with non-naturally occurring modifications, such as nucleobase or sugar modifications, that can support protein synthesis, amino acid introduction, and interaction with elongation factors, while maintaining specific structural and functional properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If non-naturally occurring modifications are introduced into tRNA to enhance protein synthesis and amino acid introduction, then the ability to support protein synthesis and amino acid incorporation is improved, but the risk of disrupting cellular processes 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 across the entire structure. The modification patterns are designed to be site-specific, affecting only certain nucleotides while leaving other regions unchanged, thereby enhancing protein synthesis function while preserving essential cellular processes.
Solution Approach 2:
The patent employs parameter changes by systematically varying the type, position, and extent of non-naturally occurring modifications in tRNA molecules. Different modification parameters (chemical group type, modification density, specific nucleotide positions) are optimized to achieve enhanced productivity while maintaining reliability, allowing precise control over the balance between improved function and cellular compatibility.
2Adaptability or versatility
If multiple non-naturally occurring modifications are introduced into tRNA nucleotides, then the modulation of tRNA functions is enhanced, but the complexity of the molecular structure increases
Solution Approach 1:
The patent applies segmentation by dividing the tRNA molecule into distinct functional domains and introducing modifications in a segmented manner. Different regions of the tRNA (such as the anticodon loop, acceptor stem, and variable regions) are modified independently with specific non-naturally occurring groups, allowing versatile function modulation while managing structural complexity through organized, region-specific modifications.
Solution Approach 2:
The patent employs composite materials by creating hybrid tRNA structures that combine natural nucleotides with non-naturally occurring modified nucleotides. This composite approach allows the molecule to retain its fundamental tRNA structure and function while incorporating diverse chemical modifications (such as fluorinated bases, modified sugars, or alternative backbone linkages) to enhance adaptability and versatility.
Data Source
AI summary
The invention relates generally to tRNA-based effector molecules having a non-naturally occurring modification and methods relating thereto.