Holliday Junction Nucleic Acid Structure for Simple Biomolecule Detection

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Solution Overview

Problem

Existing techniques for detecting nucleic acids and other biomolecules require complex methods such as fluorescent detection or atomic force microscopy, making them cumbersome and less accessible.

Innovation Solution

A nucleic acid structure comprising linked partial nucleic acid structures with Holliday junctions, containing nucleic acid aptamer sequences and split enzyme domains, which undergo structural changes upon binding to recognition substances, enabling easy detection through enzymatic activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If fluorescent detection or atomic force microscopy is used to detect structural changes of DNA origami pliers, then detection capability is achieved, but device complexity and operational difficulty increase

Engineering Contradiction:
Improvedetection capabilityVSAvoidcomplexity of detection method
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical detection systems (fluorescent microscopy, atomic force microscopy) with a simple colorimetric enzymatic detection system. The DNA origami pliers are designed to release a chromogenic substrate upon conformational change, which is then detected by a simple color change assay using a chromogenic substrate and chromogen, eliminating the need for complex imaging equipment.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The DNA origami pliers perform self-detection through their own conformational changes. The structural transition from closed to open state automatically triggers the release of chromogenic substrate, which then undergoes enzymatic conversion to produce a visible color change, allowing the structure to detect itself without external intervention.

Inventive Principle:
Principle #25Self-service

2Measurement precision

If fluorescent detection of small fluorescence intensity changes is used, then detection sensitivity is achieved, but ease of operation decreases

Engineering Contradiction:
Improvedetection sensitivityVSAvoidease of detection operation
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent employs color changes as the detection signal instead of fluorescent intensity changes. The chromogenic substrate undergoes enzymatic conversion that produces a visible color change, which can be detected by simple visual inspection or basic colorimetric assays, making the detection process straightforward and accessible without requiring sophisticated fluorescent measurement equipment.

Inventive Principle:
Principle #32Color changes

Solution Approach 2:

The patent substitutes complex fluorescent detection systems with simple colorimetric detection. The enzymatic conversion of chromogenic substrate produces a color change that can be detected by basic means, replacing the need for sensitive fluorescent instruments while maintaining adequate detection sensitivity.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Measurement precision

If detection requires complex methods such as fluorescent detection or atomic force microscopy, then detection accuracy is achieved, but ease of manufacture and accessibility worsen

Engineering Contradiction:
Improvedetection accuracyVSAvoidease of detection system manufacturing
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent uses disposable, inexpensive chromogenic substrates and simple enzymatic reagents instead of expensive, complex detection equipment. The chromogenic substrate can be easily synthesized and disposed of after use, eliminating the need for costly fluorescent dyes, microscopes, or atomic force microscopy instruments, thereby making the detection system more accessible and easier to manufacture.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent replaces complex mechanical detection systems with simple chemical enzymatic reactions. The chromogenic substrate undergoes enzymatic conversion that produces a visible color change, which can be detected by simple colorimetric assays, eliminating the need for expensive fluorescent instruments or atomic force microscopy equipment.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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

Facilitates simple and effective detection of test substances by monitoring structural transitions in the nucleic acid structure, allowing for easy identification of nucleic acids, proteins, peptides, and other biomolecules.

Implementation Method 1

the partial nucleic acid structure 1 comprising a protruding structure 1a containing a nucleic acid aptamer sequence

Methodology Applied
Scientific EffectComplementary base pairing:

Implementation Method 2

the partial nucleic acid structure 1 and the partial nucleic acid structure 2 being linked by a Holliday junction

Methodology Applied
Scientific EffectHolliday junction conformational changes:

Implementation Method 3

a protruding structure 1b containing a split domain 1 of an enzyme, and a protruding structure 2b containing a split domain 2 paired with the split domain 1

Methodology Applied
Scientific EffectEnzyme assembly and catalysis: Enzyme

Data Source

PatentUS20250283150A1Nucleic acid structure
Publication Date: 2025.09.11 CRANEBIO CO LTD
  • US20250283150A1 patent drawing
  • US20250283150A1 patent drawing
  • US20250283150A1 patent drawing

AI summary

An object is to provide a technique for detecting a test substance more easily using a nucleic acid structure. The object is achieved by a nucleic acid structure comprising a partial nucleic acid structure 1 and a partial nucleic acid structure 2, the partial nucleic acid structure 1 and the partial nucleic acid structure 2 being linked by a Holliday junction, the partial nucleic acid structure 1 comprising a protruding structure 1a containing a nucleic acid aptamer sequence, and a protruding structure 1b containing a split domain 1 of an enzyme, and the partial nucleic acid structure 2 comprising a protruding structure 2a containing a sequence complementary to part or all of the nucleic acid aptamer sequence, and a protruding structure 2b containing a split domain 2 paired with the split domain 1.