DNA-Peptide Hybrid DLISA for SARS-CoV-2 Variant Detection
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Solution Overview
Problem
Current diagnostic tests for SARS-CoV-2, particularly antigen-detecting rapid diagnostic tests (Ag-RDTs), struggle to effectively identify various variants of the virus due to mutations in the spike protein, leading to reduced sensitivity and specificity, especially in the presence of emerging variants of concern (VOCs).
Innovation Solution
A method and kit utilizing a DNA-peptide hybrid molecule, comprising a nanobody linked to a solid support and a DNA nanostructure with target-specific binding peptides, specifically designed to bind SARS-CoV-2, followed by a detection molecule with a fluorescent signal for accurate detection, including variants like alpha, beta, and delta.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional antigen-detecting rapid diagnostic tests (Ag-RDTs) are used, then the test can be performed rapidly and simply, but the sensitivity and specificity are reduced when detecting SARS-CoV-2 variants due to spike protein mutations
Solution Approach 1:
The invention segments the detection approach by using multiple different capture molecules (antibodies or antigens) that recognize different epitopes or regions of the SARS-CoV-2 virus. This segmentation allows the test to detect various viral variants even if one epitope mutates, as other epitopes remain recognizable. The segmented approach maintains rapid detection while improving measurement precision across variants.
Solution Approach 2:
The invention implements universality by designing a detection system with multiple capture molecules that can universally detect diverse SARS-CoV-2 variants. The plurality of capture molecules targets different regions of the virus, making the test functionally universal across various strains including alpha, beta, gamma, and delta variants. This multi-functionality resolves the contradiction by maintaining both rapid detection capability and high sensitivity/specificity across variant types.
2Device complexity
If capture molecules target a single epitope of SARS-CoV-2, then the assay is simple and specific, but it fails to detect variants with mutations in that epitope
Solution Approach 1:
The invention applies universality by employing multiple capture molecules that recognize different epitopes of SARS-CoV-2. This allows the relatively simple assay format to gain enhanced adaptability, detecting wild-type and variant viruses simultaneously. The multi-epitope approach maintains procedural simplicity while dramatically improving variant detection capability.
Solution Approach 2:
The invention uses composite detection reagents comprising multiple different capture molecules (antibodies or antigens) working together in a single assay. This composite approach combines the binding capabilities of multiple molecules targeting different viral regions, creating a detection system that is both simple to perform and highly adaptable to various viral variants.
3Adaptability or versatility
If multiple capture molecules targeting different epitopes are used, then variant detection capability is improved, but the assay complexity increases
Solution Approach 1:
The invention merges multiple capture molecule functionalities into a single integrated assay protocol. By combining multiple antibodies or antigens that target different epitopes into one detection system, the invention achieves improved variant detection capability without proportionally increasing procedural complexity. The merged approach allows simultaneous multi-epitope detection using a unified assay format.
Solution Approach 2:
The invention implements universality by designing a detection system where multiple capture molecules work together in a single assay to provide broad variant detection. This multi-functional approach allows the assay to handle diverse SARS-CoV-2 variants while maintaining relatively simple procedures, as all capture molecules are used concurrently in the same detection workflow rather than requiring separate tests.
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
Enhances the sensitivity and specificity of SARS-CoV-2 detection by effectively binding to multiple variants, allowing for rapid and reliable identification using automated readers or smartphones, even in the presence of variant strains.
Implementation Method 1
contacting the sample to a capture molecule, the capture molecule comprising a nanobody specific for SARS-CoV-2, wherein the capture molecule is linked to a solid support; incubating the sample in the presence of the capture molecule under conditions for SARS-CoV-2 in the sample to bind to the capture molecule
Implementation Method 2
contacting the V-AB complex with a detection molecule under conditions to allow the detection molecule to bind the V-AB complex, the detection molecule comprising a DNA-peptide hybrid molecule, the DNA-peptide hybrid molecule comprising a DNA nanostructure chemically linked to one or more target-specific binding peptides, wherein the target-specific binding peptides specifically binds SARS-CoV-2
Implementation Method 3
the detection molecule comprises a fluorescent molecule. In some embodiments of the methods, the detecting of step iv) comprises detecting a fluorescent signal from the detection molecule
Data Source
AI summary
The present disclosure relates to the use of DNA-peptide hybrid molecules to detect target molecules in a sample. In some embodiments, the DNA-peptide hybrid molecules comprise target-specific binding peptides which selectively bind to a target molecule. Kits comprising DNA-peptide hybrid molecules are also provided.