REVERSIR Compounds for Sequence-Dependent siRNA Activity Control
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Solution Overview
Problem
Existing siRNA therapeutics face challenges in achieving tailored control over RNAi pharmacology and managing therapeutic activity and side effects in vivo.
Innovation Solution
Development of REVERSIR compounds, which are oligomeric and complementary to siRNA strands, modulating their activity through sequence-dependent hybridization, including modifications such as phosphorothioate internucleoside linkages, 2′-O-methyl and 2′-O-methoxyethyl sugars, and locked nucleic acids, to inhibit or reverse siRNA activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If siRNA compounds are used to modulate target nucleic acids, then therapeutic activity is achieved, but side effects occur and control over RNAi pharmacology is limited
Solution Approach 1:
The patent introduces REVERSIR compounds as intermediary molecules that mediate the interaction between siRNA and its target. These compounds bind to siRNA and prevent siRNA from binding to its target nucleic acid, thereby controlling and reversing RNAi activity. This intermediary approach allows precise control over therapeutic effects while minimizing harmful side effects.
Solution Approach 2:
The patent employs various chemical modifications to change the parameters of siRNA compounds, including phosphorothioate internucleoside linkages, 2′-O-methyl and 2′-O-methoxyethyl sugar modifications, and locked nucleic acid structures. These parameter changes alter the pharmacological properties of siRNA, enabling tailored control over RNAi activity and reducing side effects.
2Reliability
If siRNA compounds are used for therapeutic purposes, then target nucleic acid modulation is achieved, but tailored control over RNAi pharmacology is difficult
Solution Approach 1:
The patent segments the control mechanism into two independent components: the siRNA compound that provides therapeutic activity and the REVERSIR compound that provides control. This segmentation allows independent optimization of each component's properties, enabling tailored control over RNAi pharmacology while maintaining therapeutic effects.
Solution Approach 2:
The patent creates a dynamic control system where REVERSIR compounds can be administered to modulate siRNA activity in real-time. This dynamic approach allows flexible adjustment of RNAi pharmacology based on therapeutic needs, providing adaptability and versatility in controlling therapeutic effects.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
REVERSIR compounds effectively modulate siRNA activity, providing rapid and dose-dependent reversal of RNAi, reducing side effects and enhancing therapeutic control in vivo.
Implementation Method 1
the REVERSIR compounds modulate hybridize or bind siRNA molecule in a sequence dependent manner
Data Source
AI summary
The present invention relates, in general to agents that modulate the pharmacological activity of conjugated siRNAs.