Aptamer Switch Polynucleotides With Decoupled Binding and Response

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Solution Overview

Problem

Existing aptamer switches have intrinsically coupled thermodynamic and kinetic properties, requiring high temporal resolution to be achieved at the cost of lower sensitivity, limiting their applicability in diverse applications.

Innovation Solution

Aptamer switch polynucleotides with independently tunable kinetics and effective binding affinity are developed by adjusting the length of the intramolecular linker, displacement strand, and sequence to decouple these properties, enabling a range of dissociation constants and binding kinetics suitable for various applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If existing aptamer switches are designed to achieve high temporal resolution, then response speed is improved, but sensitivity deteriorates

Engineering Contradiction:

Improveresponse speedVSAvoidsensitivity

Core Design Contradiction:

SpeedVSMeasurement precision

Solution Approach 1:

The aptamer switch is segmented into distinct functional modules: a target-binding aptamer domain, a linker region, and a displacement strand. This segmentation allows independent optimization of each module's properties, enabling the binding domain to maintain high sensitivity while the overall switch architecture achieves rapid response through controlled displacement kinetics

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention employs parameter changes by systematically varying the length and sequence composition of the linker and displacement strand. By adjusting these parameters, the invention decouples the relationship between response speed and sensitivity, allowing high temporal resolution to be achieved without sacrificing binding sensitivity through optimized kinetic parameters rather than compromising binding affinity

Inventive Principle:

Principle #35Parameter changes

2Productivity

If aptamer switch polynucleotides are designed with fixed properties, then development time is reduced, but adaptability to different applications deteriorates

Engineering Contradiction:

Improvedevelopment timeVSAvoidadaptability to applications

Core Design Contradiction:

ProductivityVSAdaptability or versatility

Solution Approach 1:

The invention creates a universal aptamer switch platform with standardized modular components that can be adapted to different target analytes and applications. The conserved structural framework and interchangeable aptamer-binding domains enable rapid adaptation to diverse targets while maintaining consistent performance characteristics, eliminating the need to redesign entire switch architectures for each application

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention enables adaptability through systematic parameter variation in the linker and displacement strand regions. By changing parameters such as linker length, nucleotide composition, and displacement strand sequence, the same basic switch architecture can be tuned for different kinetic profiles and binding affinities, providing application-specific optimization without requiring complete redesign

Inventive Principle:

Principle #35Parameter changes

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 aptamer switch polynucleotides achieve efficient development of switches with tailored characteristics, allowing for high sensitivity and rapid response times, suitable for diverse applications.

Implementation Method 1

the displacement strand is at least partially complementary to a portion of the aptamer

Methodology Applied

Scientific EffectHybridization: Chemical Bonding

Implementation Method 2

the concentration of a target analyte causes a shift in equilibrium between a reporting state and a non-reporting state of the aptamer switch polynucleotide

Methodology Applied

Scientific EffectMolecular recognition and binding: Absorption (physical)

Implementation Method 3

the fluorophore produces fluorescence as a detectable readout in the reporting state of the aptamer switch polynucleotide

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Implementation Method 4

The quencher can quench the fluorescence from the fluorophore in the non-reporting state of the aptamer switch polynucleotide

Methodology Applied

Scientific EffectQuenching: Absorption (EM radiation)

Data Source

PatentUS20260035704A1Compositions and methods involving aptamer switch polynucleotides

Publication Date: 2026.02.05 CZ BIOHUB SF LLC

AI summary

The disclosure provides aptamer switch polynucleotides whose kinetics and effective binding affinity to a target analyte can be independently tuned. The aptamer switch polynucleotides comprise an aptamer, an intramolecular linker, and a displacement strand.