Functional Ligands to LL37 for Psoriasis Treatment
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Solution Overview
Problem
Current treatments for psoriasis and rosacea, particularly those targeting LL37, lack effective and specific therapeutic agents that can inhibit LL37's inflammatory and autoimmune responses, leading to chronic skin inflammation and quality of life impairments.
Innovation Solution
Development of functional ligands, specifically nucleic acids and peptides, that bind with high affinity to LL37, using SELEX methods to generate aptamers that can inhibit LL37's action in inflammation, allowing for potential therapeutic applications in psoriasis and rosacea.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current systemic immune suppressors are used to treat psoriasis and rosacea, then inflammatory responses are suppressed, but specificity and effectiveness are insufficient leading to chronic skin inflammation
Solution Approach 1:
The patent introduces functional ligands (aptamers) as intermediary molecules that specifically bind to LL37, preventing it from interacting with its inflammatory targets. These ligands act as mediators between LL37 and the inflammatory pathway, blocking the harmful interaction without suppressing the entire immune system, thereby resolving the contradiction between effectiveness and harmful side effects
Solution Approach 2:
The patent changes the binding parameters of LL37 by introducing high-affinity ligands that alter LL37's interaction profile. By changing the binding affinity and specificity parameters through aptamer-LL37 complex formation, the inflammatory response is modulated more precisely, improving treatment effectiveness while reducing chronic inflammation
2Measurement precision
If aptamers are developed to bind LL37 with high affinity, then specificity and effectiveness are improved, but manufacturing complexity increases
Solution Approach 1:
The patent employs SELEX (Systematic Evolution of Ligands by EXponential enrichment) methodology where the aptamer library undergoes self-selection and self-optimization through iterative binding and amplification cycles. The system automatically enriches high-affinity binders without requiring complex external intervention, thereby achieving high binding affinity while simplifying the manufacturing process
Solution Approach 2:
The patent combines multiple process steps (binding selection, amplification, and enrichment) into the integrated SELEX workflow. By merging these operations into a unified iterative process, the patent achieves high-affinity aptamer development without proportionally increasing manufacturing complexity, as the same system performs multiple functions
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
The functional ligands effectively inhibit LL37's inflammatory pathways, providing a promising therapeutic approach to manage psoriasis and rosacea by targeting the underlying autoimmune responses, potentially offering a more specific and effective treatment than existing systemic immune suppressors.
Implementation Method 1
Aptamers are typically characterized by binding to their target molecules via non-Watson-Crick (i.e. non-hybridization) mechanisms, such as by intermolecular forces resulting from the secondary or tertiary structure of the aptamer
Data Source
AI summary
The present invention relates functional ligands to target molecules, particularly to functional nucleic acids and modifications thereof, and to methods for simultaneously generating, for example, numerous different functional biomolecules, particularly to methods for generating numerous different functional nucleic acids against multiple target molecules simultaneously. The present invention further relates to functional ligands which bind with affinity to target molecules, such as molecules used proteins or peptides, such as LL37.