Dimer Antibody Binding to Norovirus
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Solution Overview
Problem
Current antibodies are not effective in binding to norovirus, particularly the GII/4 strain, with existing antibodies having high dissociation constants that limit their binding affinity.
Innovation Solution
A dimer antibody is developed with specific amino acid sequences for its structural domains, linked with a linker, which enhances its binding ability to norovirus by reducing the dissociation constant significantly.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If monomer antibodies are used to bind norovirus, then the device complexity is low, but the binding affinity is insufficient with high dissociation constants
Solution Approach 1:
The patent combines two monomer antibody structures into a dimer antibody configuration, where two binding domains are linked together to form a single functional unit. This merging approach doubles the binding sites for norovirus, significantly enhancing binding affinity and reducing dissociation constants from the nanomolar range to picomolar range, while maintaining manageable structural complexity through controlled dimerization
2Reliability
If dimer antibody structure is adopted to enhance binding ability, then the binding affinity improves with lower dissociation constants, but the device complexity increases
Solution Approach 1:
The dimer antibody is designed as two separate but identical binding domains (monomers) that are independently structured and then linked together. Each domain maintains its own antigen-binding site with specific CDR regions, allowing the complex dimer structure to be understood and produced as repeated modular units, thus managing complexity through standardization
Solution Approach 2:
The patent optimizes specific parameters including the linker length and composition between the two antibody domains, the amino acid sequences in CDR regions, and the overall spatial arrangement to achieve maximum binding affinity. By carefully adjusting these parameters, the dimer structure achieves picomolar dissociation constants while keeping the structural complexity at manageable levels
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 dimer antibody exhibits a stronger binding ability to norovirus compared to monomer antibodies, with a dissociation constant of approximately 0.01-0.5 nM, effectively recognizing and binding to the virus.
Implementation Method 1
the dimer antibody exhibits a stronger binding ability to norovirus compared to monomer antibodies, with a dissociation constant of approximately 0.01-0.5 nM, effectively recognizing and binding to the virus
Data Source
AI summary
Provided is a dimer antibody including two structural domains independently each represented by the following amino acid sequence, in an N- to C-direction,N-FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4-Cwhereinthe antibody is capable of binding to a norovirus;FR denotes a framework region amino acid sequence and CDR denotes a complementary determining region amino acid sequence;any one of the following requirements (i)-(iii) is satisfied.Requirement (i):the CDR1 includes an amino acid sequence having a sequence identity of not less than 60% with any one of the amino acid sequences represented by SEQ ID NO: 1-SEQ ID NO: 6,the CDR2 includes an amino acid sequence having a sequence identity of not less than 60% with any one of the amino acid sequences represented by SEQ ID NO: 7-SEQ ID NO: 12, andthe CDR3 includes an amino acid sequence having a sequence identity of not less than 60% with any one of the amino acid sequences represented by SEQ ID NO: 13-SEQ ID NO: 17;Requirement (ii):the CDR1 includes an amino acid sequence in which one-three amino acid(s) of any one of the amino acid sequence represented by SEQ ID NO: 1-SEQ ID NO: 6 has/have been substituted, deleted, or added,the CDR2 includes an amino acid sequence in which one-three amino acid(s) of any one of the amino acid sequence represented by SEQ ID NO: 7-SEQ ID NO: 12 has/have been substituted, deleted, or added, andthe CDR3 includes an amino acid sequence in which one-three amino acid(s) of any one of the amino acid sequence represented by SEQ ID NO: 13-SEQ ID NO: 17 has/have been substituted, deleted, or added; andRequirement (iii):the CDR1 includes any one of the amino acid sequence represented by SEQ ID NO: 1-SEQ ID NO: 6,the CDR2 includes any one of the amino acid sequence represented by SEQ ID NO: 7-SEQ ID NO: 13, andthe CDR3 includes any one of the amino acid sequence represented by SEQ ID NO: 13-SEQ ID NO: 17.