Cross-Linked Nucleic Acid Affinity Reagents for Stable Analyte Binding
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Solution Overview
Problem
Nucleic acid based affinity reagents face stability issues due to dynamic 3D structure changes, leading to partial unfolding or misfolding, which complicates their use and storage, and affect the efficacy of binding to target molecules.
Innovation Solution
A nucleic acid backbone with specific reaction moieties configured to form cross-links, maintaining a stable complex structure through covalent bonds, such as CuAAC or SpAAC, to ensure robust binding to target analytes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If nucleic acid based affinity reagents are used, then cost-effectiveness and ease of production are improved, but structural stability and reliability deteriorate due to dynamic 3D structure changes
Solution Approach 1:
The patent combines nucleic acid backbone with protein elements to create a hybrid affinity reagent structure. This composite approach integrates the cost-effectiveness and ease of production of nucleic acid-based reagents with the structural stability and reliability of protein-based reagents, resolving the contradiction between manufacturability and structural integrity
Solution Approach 2:
The patent modifies the physical and chemical parameters of the affinity reagent by incorporating stabilized 3D structures with controlled folding patterns. This allows the nucleic acid backbone to maintain its production advantages while achieving enhanced structural stability through parameter optimization of the molecular conformation
2Reliability
If nucleic acid based affinity reagents are used, then affinity and specificity are improved, but ease of use deteriorates due to refolding requirements
Solution Approach 1:
The patent implements preliminary stabilization of the 3D structure during the reagent design and production phase. By pre-establishing stable folded structures with defined binding conformations, the reagent arrives ready-to-use without requiring refolding operations, thus maintaining high binding specificity while improving ease of use
Solution Approach 2:
The patent designs affinity reagents with inherently stable structures that maintain their binding capability throughout their operational lifespan without requiring refolding or reactivation. This disposable-ready design eliminates the need for complex handling procedures while preserving high affinity and specificity
3Ease of manufacture
If nucleic acid based affinity reagents are used, then cost-effectiveness is improved, but storage stability deteriorates due to partial unfolding
Solution Approach 1:
The patent creates a composite structure combining nucleic acid backbone with stabilizing elements that protect against unfolding during storage. This hybrid approach maintains the cost-effectiveness of nucleic acid production while adding structural features that extend storage stability and prevent partial unfolding
Solution Approach 2:
The patent incorporates structural features and protective elements during the design phase that cushion against environmental stresses during storage. This preemptive stabilization prevents partial unfolding and misfolding before they occur, extending the shelf life while maintaining cost-effectiveness
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 cross-linked nucleic acid backbone provides a stable and robust affinity reagent with high specificity and stability, enabling efficient binding to target analytes even under varying conditions.
Implementation Method 1
The nucleic acid backbone comprises at least one pair of reaction moieties for cross-linking the nucleic acid backbone
Implementation Method 2
The binding of the affinity reagent to the target analyte may comprise intermolecular forces such as hydrogen bonding, dipole-dipole interactions, ionic interactions, π-stacking, hydrophobic interaction, and van der Waals forces
Implementation Method 3
The binding of the affinity reagent to the target analyte may comprise intermolecular forces such as hydrogen bonding, dipole-dipole interactions, ionic interactions, π-stacking, hydrophobic interaction, and van der Waals forces
Implementation Method 4
The binding of the affinity reagent to the target analyte may comprise intermolecular forces such as hydrogen bonding, dipole-dipole interactions, ionic interactions, π-stacking, hydrophobic interaction, and van der Waals forces
Data Source
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AI summary
An affinity reagent (102, 102a, 102b) for analysing a biological sample is provided. The affinity reagent (102, 102a, 102b) comprises a nucleic acid backbone (200, 300, 402). The nucleic acid backbone (200, 300, 402) is configured to specifically bind to a target analyte (106) by its complex structure (400c). Further, the nucleic acid backbone (200, 300, 402) comprises at least one pair of reaction moieties (202, 204, 302, 304, 308, 310) for cross-linking the nucleic acid backbone (200, 300, 402). In further aspects, a marker and a method for analysing a biological sample are provided.