Circular Polyribonucleotide Composition for Persistent Cellular Translation
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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 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 controlled protein expression and persistence in cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If linear polyribonucleotides are used, then they can be synthesized and expressed, but they exhibit low translation efficiency and high immunogenicity
Solution Approach 1:
The patent applies curvature by transforming the linear polyribonucleotide into a circular structure. This circular configuration eliminates the 5' and 3' ends that trigger immune recognition, thereby reducing immunogenicity while maintaining or enhancing translation efficiency through continuous ribosomal movement along the circular template.
Solution Approach 2:
The patent changes the topological parameter of the polyribonucleotide from linear to circular configuration. This structural parameter change fundamentally alters the molecule's interaction with cellular machinery, enabling persistent translation without the degradation and immune responses associated with linear RNAs.
2Duration of action of stationary object
If linear polyribonucleotides are used, then they can be introduced into cells, but they are rapidly degraded and have short half-life
Solution Approach 1:
The circular configuration provides structural stability that resists exonuclease degradation. Without free ends, the circular RNA cannot be attacked by exonucleases that target linear RNA ends, thereby extending half-life and improving cellular stability.
Solution Approach 2:
The patent converts the potential harm of end-exposure (which invites degradation and immune recognition) into a benefit by eliminating the ends entirely. The circular structure transforms the vulnerable linear configuration into a protected continuous loop that resists cellular degradation mechanisms.
3Duration of action of moving object
If linear polyribonucleotides are used, then they can be expressed transiently, but they lack persistence during cell division
Solution Approach 1:
The circular structure enables the RNA to persist through cell division because it lacks ends that would otherwise be susceptible to degradation during the cell cycle. The continuous circular template ensures translation can be maintained across generations of dividing cells.
Solution Approach 2:
The circular polyribonucleotide enables continuous translation action without termination. Ribosomes can circulate continuously along the circular template, and the structure persists through cell division, maintaining productive translation across cell generations unlike linear RNAs that are degraded during mitosis.
Data Source
AI summary
This invention relates generally to pharmaceutical compositions and preparations of circular polyribonucleotides and uses thereof.