Antisense Oligomers Modulating IL-17 and IL-23 Signaling
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Solution Overview
Problem
Current therapies for immune-related and inflammatory diseases are inadequate, and animal models that accurately mimic human immune responses are lacking, particularly for diseases mediated by the IL-23/17 signaling pathways, which are crucial for developing effective immunomodulatory therapies.
Innovation Solution
The use of antisense oligomers targeting the IL-23/17 signaling pathways, specifically designed to modulate IL-17 and IL-23 signaling activity by hybridizing with pre-mRNA transcripts of IL-17, IL-23, IL-17RA, IL-17RC, and IL-23R, to alter splicing and expression of these proteins, thereby reducing or enhancing inflammatory responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapies are used for immune-related and inflammatory diseases, then treatment is provided, but the therapies are inadequate and do not effectively modulate IL-17 and IL-23 signaling pathways
Solution Approach 1:
The patent uses antisense oligomers as intermediary molecules that specifically bind to and modulate IL-17 and IL-23 signaling pathway components. These oligomers act as mediators between the therapeutic agent and the target pathway, providing both effectiveness and pathway specificity by selectively interfering with key signaling molecules in the IL-17/IL-23 axis without broadly suppressing immune function.
Solution Approach 2:
The invention changes the therapeutic parameter from non-specific immune suppression to specific pathway modulation by using antisense oligomers that target particular mRNA transcripts in the IL-17/IL-23 signaling pathway. This allows precise control over which pathway components are inhibited, achieving both therapeutic effectiveness and pathway adaptability.
2Adaptability or versatility
If animal models are used to develop immunomodulatory therapies, then disease research is enabled, but the models do not accurately mimic human immune responses
Solution Approach 1:
The patent applies local quality by using antisense oligomers that specifically target human-derived IL-17 and IL-23 pathway components. This allows the creation of more accurate animal models where human-specific pathway elements are selectively modulated, improving model accuracy while maintaining the ability to translate findings to human therapeutic responses.
3Object-affected harmful factors
If broad immune suppression is used to treat inflammatory diseases, then inflammation is reduced, but specificity for IL-17 and IL-23 pathways is lost
Solution Approach 1:
The invention extracts and isolates the specific IL-17 and IL-23 pathway components from the broader immune system by using antisense oligomers that selectively target these pathways. This allows reduction of harmful inflammatory responses while preserving other immune functions, achieving both anti-inflammatory effect and pathway selectivity through targeted molecular interference.
Data Source
AI summary
Provided are antisense oligonucleotides and other agents that target and modulate IL-17 and/or IL-23 signaling activity in a cell, compositions that comprise the same, and methods of use thereof. Also provided are animal models for identifying agents that modulate 17 and/or IL-23 signaling activity.