Mutated Ferritin Protein for Reduced Transferrin Receptor Binding
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Solution Overview
Problem
Current drug delivery systems face challenges in efficiently delivering proteins/peptides into cells with minimal toxicity and high efficacy, as existing methods like cationic liposomes and nanoparticles are toxic and labor-intensive, and lack universal applicability for a wide range of proteins/peptides.
Innovation Solution
A novel ferritin protein is developed with a foreign peptide fused to its surface, mutated to reduce binding to the human transferrin receptor, allowing for efficient intracellular delivery while maintaining pharmacological activity and biocompatibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If ferritin protein is used for drug delivery, then intracellular delivery efficiency is improved, but binding to human transferrin receptor causes toxicity and reduces biocompatibility
Solution Approach 1:
The patent extracts and removes the problematic binding interface between ferritin and human transferrin receptor by introducing mutations at specific amino acid positions (E117A, K120A, D124A). This eliminates the harmful binding interaction while preserving the beneficial intracellular delivery capability of ferritin.
Solution Approach 2:
The patent changes the chemical parameters of the ferritin protein by mutating specific amino acid residues. These parameter changes alter the binding characteristics of ferritin to reduce affinity for human transferrin receptor, thereby reducing toxicity while maintaining delivery efficiency.
2Reliability
If foreign peptide is fused to ferritin surface, then pharmacological activity is enhanced, but immunogenicity increases
Solution Approach 1:
The patent converts the potentially harmful immunogenicity of foreign peptide fusion into a beneficial feature by selecting immune checkpoint molecules as the foreign peptides. These peptides modulate the immune system to enhance anti-tumor immunity while reducing unwanted immunogenic responses against the ferritin carrier itself.
3Object-affected harmful factors
If mutations are introduced to reduce transferrin receptor binding, then biocompatibility is improved, but delivery efficiency may be reduced
Solution Approach 1:
The patent applies local quality changes by introducing mutations only at specific localized positions (E117, K120, D124) on the ferritin surface that are involved in transferrin receptor binding. These localized changes reduce harmful binding without affecting the overall structural integrity and delivery efficiency of the ferritin nanoparticle.
Solution Approach 2:
The patent uses partial action by mutating only the critical amino acid residues necessary for transferrin receptor binding, rather than making comprehensive changes to the entire ferritin structure. This partial modification is sufficient to reduce toxicity while preserving the essential delivery function.
Data Source
AI summary
A ferritin protein is mutated to have a foreign peptide fused to the outer surface thereof so that a binding force to a human transferrin receptor is reduced. The peptide can exhibit activities of various foreign peptides. The foreign peptide is a pharmacologically active peptide, and the foreign peptide may include a ligand or a fragment thereof, a receptor or a fragment thereof, an antibody or a fragment thereof including an antigen binding region (CDR), which are capable of binding to an immune checkpoint molecule; or a disease antigen epitope.