DNA Aptamer for Methylated DNA Detection

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Solution Overview

Problem

Current methods for detecting methylated DNA fragments, such as Methylated DNA Immunoprecipitation (MeDIP), face challenges like high cost and non-specific binding due to the use of antibodies, lacking effective alternatives for capturing and detecting these fragments.

Innovation Solution

Development of a DNA aptamer specifically binding to methylated DNA fragments, selected from sequences like SEQ ID NO:7 and SEQ ID NO:9, which forms a complex with the aptamer and can be used for detection and amplification, along with a method involving SELEX technology to select aptamers that bind to methylated DNA fragments under specific conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If MeDIP uses monoclonal antibodies to capture methylated DNA fragments, then detection capability is achieved, but cost increases and non-specific binding occurs

Engineering Contradiction:
Improvedetection capabilityVSAvoidnon-specific binding
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent replaces antibodies with DNA aptamers that copy the binding function. The aptamers are selected through SELEX to specifically bind methylated DNA fragments, replicating the capture capability of antibodies while avoiding protein-related non-specific binding issues.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent changes the molecular type from protein (antibody) to nucleic acid (aptamer). This parameter change fundamentally alters the binding characteristics, reducing non-specific binding while maintaining detection capability through sequence-specific recognition of methylated DNA.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If MeDIP uses monoclonal antibodies to capture methylated DNA fragments, then detection capability is achieved, but cost increases

Engineering Contradiction:
Improvedetection capabilityVSAvoidcost
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent employs DNA aptamers which are chemically synthesized and generally less expensive than monoclonal antibodies. Aptamers can be produced through in vitro selection and chemical synthesis, avoiding the costly animal immunization and hybridoma production processes required for antibodies.

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

Solution Approach 2:

The aptamer system copies the functional role of antibodies but uses a cheaper molecular platform. The SELEX process generates aptamers that perform the same capture function at lower material and production costs.

Inventive Principle:
Principle #26Copying

3Measurement precision

If DNA aptamer is used to bind methylated DNA fragment, then specificity and sensitivity are improved, but selection process complexity increases

Engineering Contradiction:
Improvespecificity and sensitivityVSAvoidselection process complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The SELEX process is a self-organizing in vitro evolution system where the aptamer library automatically selects high-affinity binders through iterative binding and amplification cycles. The system self-optimizes without requiring complex external intervention, achieving high specificity through natural selection principles.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent performs preliminary selection of aptamers with high affinity and specificity for methylated DNA through multiple rounds of SELEX before application. This preliminary action ensures that the selected aptamers possess the required binding characteristics, simplifying subsequent experimental procedures.

Inventive Principle:
Principle #10Preliminary action

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 DNA aptamer demonstrates high specificity and sensitivity in capturing and detecting methylated DNA fragments, reducing costs and non-specific binding issues, enabling effective analysis of epigenetic regulation and potential therapeutic targets.

Implementation Method 1

a DNA aptamer specifically binding to a methylated DNA fragment

Methodology Applied
Scientific EffectMolecular recognition:

Data Source

PatentUS20240218375A1DNA aptamer specifically binding to methylated DNA fragment and selection method and use thereof
Publication Date: 2024.07.04 NATIONAL TSING HUA UNIVERSITY

AI summary

A DNA aptamer specifically binding to a methylated DNA fragment includes a nucleotide sequence selected from the group consisting of SEQ ID NO:7 and SEQ ID NO:9. In addition, a method for detecting a methylated DNA fragment in a sample and a method for selecting a DNA aptamer specifically binding to the methylated DNA fragment are also disclosed.