Molecular Combing DNA Damage Detection

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Solution Overview

Problem

Current methods for detecting DNA damage and repair lack sensitivity and specificity, particularly in visualizing and quantifying damage and repair events at the molecular level, which is crucial for understanding cellular responses to genotoxic agents and their implications in health and disease.

Innovation Solution

A method involving Molecular Combing or nucleic acid stretching techniques, combined with detectable nucleotides or nucleosides that interact with DNA to mark damage sites, allowing for the detection and visualization of repaired portions on stretched nucleic acids, enabling sensitive and accurate quantification of damage and repair.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional DNA damage detection methods are used, then the basic presence of damage can be detected, but sensitivity and specificity for visualizing and quantifying damage and repair events at the molecular level are insufficient

Engineering Contradiction:
Improvesensitivity and specificity of DNA damage detectionVSAvoiddifficulty in visualizing and quantifying damage and repair events
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent employs intermediaries in the form of detectable nucleotides/nucleosides that interact with DNA to mark damage sites, and stretched nucleic acids that serve as intermediaries to enable visualization and quantification of repair events at the molecular level

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces conventional mechanical/ biochemical detection systems with molecular combing and nucleic acid stretching techniques that enable direct visualization and quantification of DNA damage and repair events at the molecular level, achieving higher sensitivity and specificity

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

2Measurement precision

If molecular combing or nucleic acid stretching methods are used, then sensitivity and specificity for detecting DNA damage are improved, but the complexity of the detection system increases

Engineering Contradiction:
Improvesensitivity and specificity of damage detectionVSAvoidcomplexity of detection system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the detection process into distinct functional steps: DNA damage marking with detectable nucleotides, nucleic acid stretching, and visualization/quantification of repair events, making the complex system manageable and systematic

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent utilizes parameter changes in the form of detectable nucleotides/nucleosides that incorporate into damaged DNA, and the physical stretching of nucleic acids to alter their conformation, enabling detection while managing system complexity through controlled modifications

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

This approach provides high sensitivity and specificity in detecting and quantifying DNA damage and repair, enabling the assessment of cellular responses to genotoxic agents and aiding in the diagnosis of diseases, as well as evaluating the efficacy of therapeutic agents.

Implementation Method 1

adding a detectable nucleotide or nucleoside for a time and under conditions sufficient for interaction with nucleic acids, wherein said detectable nucleotide or nucleoside is incorporated by one or more enzymes present inside said living cells

Methodology Applied
Scientific EffectEnzyme: Enzyme

Implementation Method 2

Molecular Combing or other nucleic acid stretching methods or similar methods are employed together with compounds reacting with DNA

Methodology Applied
Scientific EffectMolecular Combing:

Data Source

PatentEP2619325B1A method for detecting, quantifying and mapping damage and/or repair of DNA strands
Publication Date: 2016.06.01 GENOMIC VISION
  • EP2619325B1 patent drawingFigure 1
  • EP2619325B1 patent drawingFigure 2~3
  • EP2619325B1 patent drawingFigure 4

AI summary

Methods and products for detecting in vitro the presence of damage on DNA or the presence of a biological response to damage on DNA at the molecular level. Molecular Combing or other nucleic acid stretching methods are employed together with compounds reacting with DNA, probes binding DNA, or nucleic acid monomers, especially labeled nucleic acid monomers.