Circularly Permuted Polypeptides for Antigen Display
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Solution Overview
Problem
There is a need for novel protein nanostructures capable of displaying various antigens beyond those currently addressed by existing designs like I53-50 and I3-01.
Innovation Solution
The development of polypeptides that are circular permutations of I53-50A, featuring an assembly domain with specific N-terminal, linking, and C-terminal polypeptide segments, allowing for self-assembly into nanostructures with accessible C termini for antigen fusion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If existing nanostructure designs (I53-50, I3-01) are used to display antigens, then vaccine candidates can be produced, but antigen accessibility and immune response enhancement are limited
Solution Approach 1:
The polypeptide is divided into distinct functional segments: an assembly domain (residues 74-201) responsible for self-assembly into nanostructures, and a C-terminal segment (residues 1-73) that remains accessible on the nanostructure surface for antigen fusion. This segmentation allows independent optimization of assembly properties and antigen display properties.
Solution Approach 2:
Instead of fusing antigens to the N-terminus or internal regions of existing nanostructure polypeptides, this invention uses circular permutation to place the antigen fusion site at the C-terminus, which becomes surface-exposed. This inverted approach to terminus utilization improves antigen accessibility and immune recognition.
2Object-affected harmful factors
If circular permutation is applied to I53-50A to create novel nanostructures, then antigen accessibility is improved, but polypeptide sequence and structural design complexity increases
Solution Approach 1:
The assembly domain (residues 74-201 of I53-50A) is designed to retain universal self-assembly functionality while allowing different antigen sequences to be fused to the C-terminus. This multi-functional design enables a single polypeptide backbone to support diverse antigen displays while maintaining consistent nanostructure formation.
Solution Approach 2:
The invention changes the topological parameters of the polypeptide through circular permutation, specifically repositioning the N- and C-termini to different locations in the folded structure. This parameter change transforms the accessibility of the C-terminus from buried to surface-exposed, enabling antigen fusion without altering the core assembly domain sequence.
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
These circularly permuted polypeptides enable the formation of nanostructures with improved antigen accessibility, potentially enhancing immune responses and vaccine efficacy.
Implementation Method 1
the polypeptides, as predicted, would self-assemble into the intended two-component nanostructure
Data Source
AI summary
The present disclosure relates to polypeptides that are circular permutations of an I53-50A nanostructure, comprising, in N- to C-terminal order, a N-terminal polypeptide segment, a linking polypeptide segment, and a C-terminal polypeptide segment.