Circular Polyribonucleotides for Targeted Pathogenic Protein Degradation
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Solution Overview
Problem
Current methods lack effective solutions for modulating substrate proteins, particularly pathogenic proteins, which are difficult to degrade due to their stability and interaction with other proteins, leading to various diseases such as cancer and neurodegenerative disorders.
Innovation Solution
The use of circular polyribonucleotides with conjugation and binding sites that target specific proteins, such as ubiquitin ligases, to recruit chemical compounds that facilitate the degradation of substrate proteins through ubiquitination and proteasomal pathways.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used to target pathogenic proteins, then specificity can be achieved, but the stability and protein-protein interactions of pathogenic proteins make degradation difficult
Solution Approach 1:
The patent employs circular polyribonucleotides as intermediary molecules that mediate between the degradation system and pathogenic proteins. These circRNAs bind to target proteins and recruit E3 ubiquitin ligases, facilitating targeted degradation while overcoming the stability and interaction barriers of pathogenic proteins through this intermediary mechanism
Solution Approach 2:
The patent utilizes chemical modifications of the circular polyribonucleotide, such as incorporating modified nucleotides with conjugation moieties, to change the chemical parameters of the circRNA. This enables covalent conjugation to chemical compounds that enhance binding affinity and degradation efficiency, thereby overcoming the stability of pathogenic proteins
2Object-affected harmful factors
If pathogenic proteins are made more stable to prevent degradation, then their harmful effects are reduced, but their stability becomes harder to overcome
Solution Approach 1:
The patent performs preliminary action by pre-modifying the circular polyribonucleotide with conjugation moieties and binding sites before it encounters the pathogenic protein. This pre-prepared circRNA can then efficiently bind to and recruit degradation machinery to stable pathogenic proteins, overcoming their stability through advance preparation
Solution Approach 2:
The patent creates a composite functional system combining circular polyribonucleotide, chemical compounds, and E3 ubiquitin ligases. This composite approach integrates multiple mechanisms (binding, recruitment, and catalysis) to overcome the stability of pathogenic proteins that single methods cannot achieve alone
3Productivity
If circular polyribonucleotides are designed with multiple conjugation moieties to enhance functionality, then degradation efficiency improves, but the complexity of the molecule increases
Solution Approach 1:
The patent segments the circular polyribonucleotide into distinct functional regions: binding sites for target proteins, conjugation moieties for chemical compound attachment, and structural elements maintaining the circular geometry. This segmentation allows each component to perform its specific function while keeping the overall design manageable and modular
Solution Approach 2:
The circular polyribonucleotide is designed with multi-functionality, serving as both a binding molecule for target proteins and a conjugation platform for chemical compounds. This universal design consolidates multiple functions into a single molecule, reducing the need for separate components and managing complexity
Data Source
AI summary
This invention relates to compositions comprising circular polyribonucleotides and uses thereof.