Multivalent Proteins for Lateral Flow Virus Detection
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Solution Overview
Problem
The COVID-19 pandemic highlighted the need for rapid, widespread, and affordable testing and therapies, particularly in low and middle-income countries, where healthcare infrastructure is limited, and existing methods like PCR-based tests require specialized equipment. Additionally, current antibody detection methods are complex and costly, and therapies for hospitalized patients are inadequate, leading to higher fatality rates.
Innovation Solution
Development of multivalent proteins that target the SARS-CoV-2 spike receptor binding domain with the human ACE2 receptor and the interaction between HIF1α and p300, utilizing a lateral flow assay for point-of-care testing and therapeutic applications, including the use of ACE-TAP and H-MAP proteins that exhibit picomolar binding affinity and can be expressed in E. coli, allowing for both diagnostic and therapeutic use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If PCR-based testing methods are used, then measurement precision is improved, but device complexity and cost increase
Solution Approach 1:
The patent replaces complex mechanical/chemical PCR systems with a simplified lateral flow assay that uses protein-protein interactions. The multivalent protein binds to viral antigens and is detected via lateral flow, eliminating the need for thermal cyclers, specialized reagents, and complex instrumentation while maintaining diagnostic utility.
Solution Approach 2:
The patent changes the detection parameter from nucleic acid amplification (PCR) to antigen-antibody binding (lateral flow). This parameter shift allows detection without specialized equipment while preserving measurement precision through the use of multivalent proteins with high binding affinity for viral targets.
2Measurement precision
If specialized testing instruments and costly reagents are used, then measurement precision is improved, but ease of manufacture and accessibility worsen
Solution Approach 1:
The patent employs disposable lateral flow test strips with pre-attached multivalent proteins, eliminating the need for expensive, reusable instrumentation. The tests are designed for single-use, simple deployment, and disposal, dramatically reducing manufacturing complexity and enabling widespread distribution to resource-limited settings.
Solution Approach 2:
The patent extracts the essential diagnostic function from complex laboratory instrumentation and embeds it directly into a simple lateral flow format. By taking out the core antigen-binding function and placing it in a portable, equipment-free format, the test achieves both precision and ease of manufacture.
3Ease of manufacture
If monomeric ligands are used for target binding, then manufacturing simplicity is improved, but binding affinity and therapeutic effectiveness worsen
Solution Approach 1:
The patent creates composite multivalent proteins by fusing multiple functional domains: the cartilage oligomeric matrix protein (COMP) coiled-coil oligomerization domain, the ACE2 N-terminal helix binding domain, and epitope tags for detection. This composite structure provides both manufacturing simplicity (single gene expression) and high binding affinity (multivalent interaction with viral RBD).
Solution Approach 2:
The patent merges multiple functional elements into a single protein construct: oligomerization capability, target binding specificity, and detection tagging. This merging allows the protein to self-assemble into multivalent structures that achieve picomolar binding affinity while maintaining ease of production through recombinant expression in E. coli.
4Loss of time
If rapid testing is implemented, then response time is improved, but measurement precision may worsen
Solution Approach 1:
The multivalent proteins are pre-engineered with high binding affinity for viral targets during the design phase. This preliminary optimization of binding kinetics ensures that rapid lateral flow detection does not compromise precision, as the pre-configured high-affinity interactions enable both speed and accuracy in a single step.
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 multivalent proteins provide a rapid, simple, and effective point-of-care test for COVID-19, capable of detecting the virus and antibodies simultaneously, and have shown potential in reducing the severity of infection and tumor growth, making them suitable for both diagnostic and therapeutic applications, especially in resource-constrained settings.
Implementation Method 1
The present disclosure provides a multivalent protein that targets the interaction of SARS-CoV-2 spike receptor binding domain (RBD) with the human angiotensin-converting enzyme 2 (ACE2) receptor protein
Implementation Method 2
a multivalent protein that targets the interaction of p300 with the hypoxia induced factor 1α (HIF1α)
Implementation Method 3
lateral flow assays (LFAs) and enzyme-linked immunosorbent assays (ELISA), represent a point-of-care (POC) test for a simple, inexpensive, and fast diagnosis
Data Source
AI summary
Provided is a multivalent protein that targets interaction of SARS-CoV-2 spike receptor binding domain (RBD) with the human angiotensin-converting enzyme 2 (ACE2) receptor protein. The multivalent proteins may also be used to treat subjects having cancer and/or a disease and/or viral infection. Also presented is a multiplex lateral flow test strips for simultaneous detection of the virus and viral antibodies.