Hybrid Circular Polyribonucleotide Composition for Low Immunogenicity
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Solution Overview
Problem
Circular polyribonucleotides in human tissues and cells exhibit high immunogenicity and instability, limiting their effective use in pharmaceutical applications.
Innovation Solution
Development of hybrid modified circular polyribonucleotides with a combination of modified and unmodified nucleotides, specifically a first portion of contiguous unmodified nucleotides, to reduce immunogenicity and enhance stability, thereby improving expression and half-life.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If circular polyribonucleotides are used in pharmaceutical applications, then they can serve as therapeutic agents, but they exhibit high immunogenicity and instability
Solution Approach 1:
The patent applies local quality by creating a hybrid modified circular polyribonucleotide where only specific portions are modified with pseudouridine or 5-methylcytidine while other portions remain unmodified. This selective modification approach allows the molecule to maintain regions that are tolerant to modifications (improving stability) while preserving regions that must remain unmodified to avoid immune recognition (reducing immunogenicity).
Solution Approach 2:
The patent creates a composite structure by combining modified and unmodified nucleotide sequences within the same circular polyribonucleotide molecule. This composite approach allows the molecule to integrate both stabilizing modifications and immunogenicity-reducing unmodified regions, achieving a balance between the two conflicting properties.
2Duration of action of stationary object
If fully modified circular polyribonucleotides are used, then stability is improved, but immunogenicity increases
Solution Approach 1:
The patent implements local quality by strategically placing modifications only in specific regions of the circular polyribonucleotide rather than uniformly throughout. The modified portions contribute to extended half-life and stability, while the unmodified portions maintain low immunogenicity, achieving both goals simultaneously.
Solution Approach 2:
The patent applies parameter changes by controlling the degree and distribution of modification within the circular polyribonucleotide. By adjusting the percentage and location of modified versus unmodified nucleotides, the patent optimizes the balance between half-life extension and immunogenicity reduction.
3Object-affected harmful factors
If unmodified circular polyribonucleotides are used, then immunogenicity is reduced, but stability and half-life are shortened
Solution Approach 1:
The patent applies local quality by creating regions of modification within the circular polyribonucleotide that specifically target stability enhancement without compromising the unmodified regions that maintain low immunogenicity. This localized approach allows simultaneous achievement of both objectives.
Solution Approach 2:
The patent creates a composite molecular structure combining modified and unmodified nucleotide sequences, where the modified portions provide stability and extended half-life while the unmodified portions maintain low immunogenicity, achieving a synergistic effect.
Data Source
AI summary
This invention relates generally to pharmaceutical compositions and preparations of modified circular polyribonucleotides and uses thereof.