Circular Polyribonucleotides for Stable Protein Expression
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Solution Overview
Problem
Existing linear polyribonucleotides face challenges in translation efficiency, immunogenicity, and stability, particularly in cellular environments, limiting their effectiveness in protein expression and therapeutic applications.
Innovation Solution
Development of circular polyribonucleotides with structural elements such as encryptogens, stagger elements, and regulatory sequences that enhance translation efficiency, reduce immunogenicity, and increase stability, allowing for rolling circle translation and persistent expression in cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If linear polyribonucleotides are used for protein expression, then translation can occur, but translation efficiency is limited and immunogenicity increases
Solution Approach 1:
The patent applies circularization of the polyribonucleotide to transform the linear structure into a circular one. This curvature change eliminates the 5' and 3' ends that trigger immunogenic responses while maintaining translation capability through rolling circle translation mechanism, thereby resolving the contradiction between translation efficiency and immunogenicity
Solution Approach 2:
The patent modifies the structural parameters of the polyribonucleotide by introducing circular topology and incorporating structural elements like stagger elements and regulatory sequences. These parameter changes enhance translation efficiency while reducing immunogenicity, directly addressing the technical contradiction
2Reliability
If linear polyribonucleotides are used, then protein expression can be achieved, but stability and half-life are reduced
Solution Approach 1:
The circular structure eliminates terminal structures that are susceptible to exonuclease degradation, thereby enhancing stability and extending half-life. The circular topology protects the polyribonucleotide from degradation mechanisms that target linear ends, resolving the contradiction between stability and half-life
Solution Approach 2:
The patent incorporates protective structural elements and modifications beforehand to prevent degradation. By designing the circular structure with protective features in advance, the polyribonucleotide gains enhanced stability and extended half-life without requiring additional protective measures during cellular processes
3Productivity
If circular polyribonucleotides are designed with multiple structural elements, then translation efficiency and stability improve, but device complexity increases
Solution Approach 1:
The patent merges multiple functional elements (expression sequences, stagger elements, regulatory elements, and structural motifs) into a single circular polyribonucleotide structure. This integration allows simultaneous achievement of enhanced translation efficiency, stability, and persistence without requiring separate components, thereby managing the complexity through functional consolidation
Data Source
AI summary
This invention relates generally to pharmaceutical compositions and preparations of circular polyribonucleotides and uses thereof.