Circular Polyribonucleotide Composition for Stable Low-Immunogenic 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 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

VSEngineering Contradiction Analysis

1Productivity

If linear polyribonucleotides are used for therapeutic applications, then they can deliver genetic material, but they exhibit low translation efficiency and high immunogenicity

Engineering Contradiction:

Improvetranslation efficiencyVSAvoidimmunogenicity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent inverts the conventional linear structure of polyribonucleotides to a circular structure. This structural inversion fundamentally changes the properties of the molecule: circular polyribonucleotides resist degradation by exonucleases (which require free ends), exhibit enhanced translation efficiency through continuous circular templates, and reduced immunogenicity by avoiding recognition as foreign linear nucleic acids by cellular immune sensors

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The patent employs composite structural elements within the circular polyribonucleotide including encryptogens (to mask immunogenicity), stagger elements (to regulate translation), and regulatory sequences (to control expression). These composite functional elements work together to achieve simultaneous improvement in translation efficiency, stability, and reduced immunogenicity

Inventive Principle:

Principle #40Composite materials

2Stability of the object's composition

If linear polyribonucleotides are used, then they can be synthesized and delivered, but they have short half-life and low stability in cellular environments

Engineering Contradiction:

ImprovestabilityVSAvoidhalf-life

Core Design Contradiction:

Stability of the object's compositionVSDuration of action of moving object

Solution Approach 1:

The circular structure eliminates free 5' and 3' ends that are susceptible to exonuclease degradation. This topological inversion provides inherent resistance to nucleolytic degradation, dramatically increasing both stability and half-life in cellular environments without requiring additional protective modifications

Inventive Principle:

Principle #13The other way round (Inversion)

3Productivity

If circular polyribonucleotides are designed with multiple functional elements, then translation efficiency and stability improve, but the structural complexity increases

Engineering Contradiction:

Improvetranslation efficiencyVSAvoidstructural complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The circular polyribonucleotide structure serves multiple functions simultaneously: the circular topology provides stability and resistance to degradation, while embedded functional elements (encryptogens, stagger elements, regulatory sequences) collectively handle translation regulation, immunogenicity masking, and expression control. This multi-functionality reduces the need for separate molecular components

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS12539309B2Compositions comprising circular polyribonucleotides and uses thereof

Publication Date: 2026.02.03 FLAGSHIP PIONEERING INNOVATIONS VI LLC

AI summary

This invention relates generally to pharmaceutical compositions and preparations of circular polyribonucleotides and uses thereof.