Immune Regulatory Oligonucleotides Modulating TLR Immune Response
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Solution Overview
Problem
Current TLR antagonists often require polyG sequences, which can form secondary structures and are not effective in inhibiting TLR9, TLR7, and TLR8-mediated immune responses, and there is a need for disease-specific and patient-specific treatments for immune-related disorders.
Innovation Solution
Development of immune regulatory oligonucleotide (IRO) compounds that act as antagonists of TLR7 and TLR9, inhibiting cytokine and chemokine profiles through specific chemical modifications and internucleotide linkages, allowing for targeted immune modulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If polyG sequences are used in TLR antagonists, then immune response inhibition is achieved, but secondary structures form reducing effectiveness
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of oligonucleotides through various modifications including phosphorothioate backbones, 2'-O-methyl ribose sugars, and locked nucleic acid (LNA) modifications. These parameter changes in molecular structure prevent secondary structure formation while maintaining TLR binding affinity and immune response inhibition effectiveness.
Solution Approach 2:
The patent employs composite materials by creating hybrid oligonucleotide structures that combine different modified nucleotides and backbone types. These composite structures integrate phosphorothioate linkages with modified sugar moieties and diverse base compositions to achieve both structural stability and functional effectiveness in inhibiting TLR-mediated immune responses without forming detrimental secondary structures.
2Reliability
If conventional TLR antagonists are used, then general immune response inhibition is achieved, but disease-specific and patient-specific treatment is not possible
Solution Approach 1:
The patent applies local quality by designing oligonucleotide sequences with specific local modifications at particular positions within the molecule. Different nucleotides at different positions can be selectively modified to target specific TLR subtypes (TLR7, TLR8, TLR9) and to create variants suited for different disease contexts, enabling both general inhibition and disease-specific adaptation.
Solution Approach 2:
The patent employs dynamics by creating a platform technology that allows flexible adaptation of oligonucleotide sequences for different applications. The modular design with variable regions enables the same basic structure to be dynamically adjusted for different diseases, patient populations, and TLR targets, transforming a static antagonist into a versatile therapeutic platform.
Data Source
AI summary
The invention provides immune regulatory oligonucleotides (IRO) as antagonist of TLRs and methods of use thereof. These IROs have unique sequences that inhibit TLR-mediated signaling in response to a TLR ligand or TLR agonist. The methods may have use in the prevention and treatment of cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen.