TREMs with ASGPR Binding for PTC Suppression
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Solution Overview
Problem
Current technologies lack effective solutions for modulating protein synthesis and treating diseases associated with premature termination codons (PTCs) in RNA molecules, particularly in addressing the challenges of protein production and signaling parameters.
Innovation Solution
Development of tRNA-based effector molecules (TREMs) with an asialoglycoprotein receptor (ASGPR) binding moiety, which can be conjugated to nucleobases or internucleotide linkages, allowing for modulation of protein synthesis and treatment of diseases by targeting premature termination codons.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional technologies are used for modulating protein synthesis, then existing methods can be applied, but they lack effectiveness in treating diseases associated with premature termination codons
Solution Approach 1:
The patent introduces TREMs as intermediary molecules that bridge the gap between conventional protein synthesis machinery and premature termination codons. These engineered tRNA-like molecules with modified anticodons specifically recognize PTC sequences and deliver amino acids to suppress termination, enabling effective treatment of PTC-associated diseases while maintaining compatibility with existing cellular translation mechanisms
Solution Approach 2:
The invention modifies key parameters of tRNA molecules including anticodon sequences, amino acid identity, and structural features to create TREMs optimized for PTC suppression. By changing these molecular parameters, the system achieves both effectiveness in treating PTC diseases and adaptability to target specific termination codons while maintaining functionality in the cellular translation system
2Productivity
If TREMs are used to modulate protein synthesis, then protein production is enhanced, but the complexity of the molecular system increases
Solution Approach 1:
The patent segments the complex task of PTC suppression into modular TREM components with distinct functional domains: anticodon recognition regions, amino acid attachment sites, and structural elements for ribosome interaction. This segmentation allows systematic design and optimization of individual modules while maintaining overall system functionality, enhancing protein production without overwhelming complexity
Solution Approach 2:
The invention creates universal TREM platforms that can be adapted to suppress different types of premature termination codons through modular anticodon design. The core structural framework and amino acid delivery mechanism remain consistent across applications, providing multi-functionality that enhances protein production for various PTC-associated diseases without requiring completely separate systems for each application
Data Source
AI summary
The invention relates generally to tRNA-based effector molecules (TREMs) comprising an asialoglycoprotein receptor (ASGPR) binding moiety, as well as compositions and methods relating thereto.