ASGR1-Binding Polypeptides for Liver-Targeted Immune Tolerance
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Solution Overview
Problem
Existing therapies fail to effectively address immune responses to antigens, particularly in autoimmune diseases and other disorders, including autoimmune diseases, by targeting the liver with therapeutic compositions, to induce antigen-specific immune tolerance.
Innovation Solution
Development of ASGR1 binding polypeptides that are conjugated or fused to antigens, which are administered to the liver to induce immune tolerance by binding to asialoglycoprotein receptor 1 (ASGR1) on liver cells, thereby promoting tolerance to antigens such as food allergens and autoantigens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If therapeutic compositions are administered systemically, then the antigen can be delivered to the liver, but the composition cannot be sufficiently targeted to liver cells resulting in poor immune tolerance induction
Solution Approach 1:
The patent employs ASGR1 binding polypeptides as intermediary molecules that mediate the delivery of tolerogenic antigens to liver cells. These polypeptides bind to the asialoglycoprotein receptor 1 on hepatocytes and liver sinusoidal endothelial cells, serving as a targeted delivery vehicle that overcomes the lack of liver specificity in systemically administered therapies.
Solution Approach 2:
The invention achieves local quality by creating liver-specific targeting through the ASGR1 binding polypeptide-antigen conjugate. The polypeptide portion provides liver-specific binding characteristics while the antigen portion provides tolerogenic activity, creating a composition with differentiated functional properties concentrated at the liver site of action.
2Reliability
If existing therapies are used to address immune responses, then treatment can be administered, but they fail to effectively induce antigen-specific immune tolerance
Solution Approach 1:
The patent changes the critical parameter of delivery specificity by incorporating ASGR1 binding polypeptides into the therapeutic composition. This parameter change transforms the composition from a non-specific systemical agent to a liver-targeted therapy, thereby improving the effectiveness of antigen-specific immune tolerance induction.
Solution Approach 2:
The invention uses composite materials by conjugating or fusing the ASGR1 binding polypeptide to the tolerogenic antigen. This creates a hybrid molecular structure combining the targeting capability of the polypeptide with the immunological activity of the antigen, achieving both liver specificity and effective immune tolerance induction simultaneously.
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 ASGR1 binding polypeptides effectively induce antigen-specific immune tolerance, reducing unwanted immune responses to food allergens and autoantigens, including autoimmune diseases, by targeting liver cells.
Implementation Method 1
binding polypeptides that bind to ASGR1... binding to asialoglycoprotein receptor 1 (ASGR1) on liver cells
Data Source
AI summary
Disclosed herein are binding polypeptides that bind to asialoglycoprotein receptor 1 (ASGR1), and methods of use thereof for inducing immune tolerance against antigens of interest, for example, for treating, ameliorating, inhibiting, or preventing disease or disorders associated with unwanted immune response against the antigens of interest, such as autoimmune diseases.