Liver-Targeted Tolerogenic Molecule for Antigen-Specific Immune Tolerance
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Solution Overview
Problem
Current methods fail to effectively induce immune tolerance to specific antigens, leading to unwanted immune responses in conditions like autoimmune diseases and allergies, as they do not efficiently target and process antigens in the liver, which is crucial for tolerogenic processes.
Innovation Solution
Development of tolerogenic molecules comprising antigens or antigen fragments linked with liver-targeting moieties, specifically designed to be processed by liver cells, such as hepatocytes, to induce immune tolerance by cross-presentation and tolerogenic mechanisms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used to induce immune tolerance, then the treatment approach is simple, but the effectiveness in inducing antigen-specific tolerance is insufficient
Solution Approach 1:
The patent combines multiple functional components into a single tolerogenic molecule: an antigen (X), a liver-targeting moiety (Z), and a linker (Y) are merged into one conjugate structure. This merging ensures the molecule can both target the liver specifically and present the antigen for tolerance induction, resolving the contradiction by integrating multiple functions into one unified structure that improves reliability without requiring separate complex systems
Solution Approach 2:
The tolerogenic molecule is constructed as a composite material combining different functional elements: the antigen component, the liver-targeting component (such as galactose or other hepatocyte-specific ligands), and the linker component. This composite structure allows each component to contribute its specific function, improving the overall effectiveness of immune tolerance induction while maintaining a manageable molecular structure
2Reliability
If antigens are not efficiently targeted to the liver, then the treatment is simple, but the processing and presentation of antigens by liver cells is insufficient
Solution Approach 1:
The liver-targeting moiety (Z) acts as an intermediary that mediates the interaction between the tolerogenic molecule and liver cells. This intermediary component (such as galactose, N-acetylgalactosamine, or other hepatocyte-specific ligands) binds to receptors on liver cell surfaces, facilitating efficient uptake and processing of the antigen by liver cells, thereby improving antigen presentation efficiency without requiring complex targeting mechanisms
Solution Approach 2:
The tolerogenic molecule is designed with localized functionality: the liver-targeting moiety is positioned to interact specifically with liver cell receptors, while the antigen component is positioned for optimal presentation. This local quality assignment ensures that each part of the molecule performs its specific function efficiently, improving antigen processing by liver cells without requiring the entire molecule to be complex
3Reliability
If conventional antigen administration is used, then the administration method is simple, but the induction of CD4+ regulatory T cells and anergic CD8+ T cells is insufficient
Solution Approach 1:
The tolerogenic molecule is designed to perform preliminary action by pre-configuring the antigen for optimal liver cell uptake and processing. The liver-targeting moiety is attached in advance to the antigen, ensuring that upon administration, the molecule is immediately recognized and internalized by liver cells, which then process and present the antigen to induce CD4+ regulatory T cells and anergic CD8+ T cells. This preliminary configuration improves tolerance induction efficiency without requiring complex administration protocols
Data Source
AI summary
Several embodiments provided in the present disclosure relate to compositions that carry an antigen to which tolerance is desired, the antigen being coupled, bound, or otherwise joined to a targeting moiety, the targeting moiety configured to direct the composition to the liver of a subject. In several embodiments, the antigen in coupled to the targeting moiety by way of a polymeric linker. In several embodiments, the polymeric linker is configured to liberate the antigen in vivo. Methods of using the compositions to reduce and/or prevent unwanted immune responses against an antigen of interest are also provided.