Oligonucleotide Probes for CYP2C9 Polymorphism Detection

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Solution Overview

Problem

Current methods for detecting CYP2C9 polymorphisms associated with adverse drug responses are not sufficiently rapid, reliable, or convenient, leading to challenges in selecting appropriate therapeutic agents and doses for individuals, which contributes to therapeutic failures and adverse drug reactions.

Innovation Solution

The development of specific oligonucleotide sequences for amplification primers and detection probes that can identify CYP2C9 single nucleotide polymorphisms (SNPs), including CYP2C9(*2), CYP2C9(*3), CYP2C9(*4), and CYP2C9(*5) alleles, enabling rapid and accurate genotyping for personalized drug regimens.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional methods are used for detecting CYP2C9 polymorphisms, then detection can be performed, but the detection is not sufficiently rapid, reliable, or convenient

Engineering Contradiction:
Improvedetection reliabilityVSAvoiddetection speed
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The invention divides the detection process into separate functional components: amplification primers for DNA amplification and detection probes for polymorphism identification. This segmentation allows each component to be optimized independently, improving both reliability and speed of detection

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The amplification primers are designed to pre-amplify specific CYP2C9 gene regions containing polymorphic sites before detection. This preliminary amplification action ensures sufficient target DNA is available for rapid and reliable detection, addressing both speed and reliability requirements

Inventive Principle:
Principle #10Preliminary action

2Ease of operation

If conventional detection methods are used, then polymorphism detection is possible, but it is not convenient for clinical application

Engineering Contradiction:
Improvedetection convenienceVSAvoiddetection reliability
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The invention combines amplification and detection functions into an integrated system where amplification primers and detection probes work together in a coordinated manner. This merging simplifies the overall workflow and improves convenience while maintaining high reliability through the specific design of matched primer-probe systems

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The detection probes serve as intermediaries that specifically bind to amplified DNA sequences containing polymorphisms. This intermediary mechanism provides a reliable and convenient bridge between DNA amplification and polymorphism identification, enhancing both ease of operation and detection reliability

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If non-specific primers are used for amplification, then amplification can occur, but CYP2C19 sequences are also amplified causing interference

Engineering Contradiction:
Improveamplification efficiencyVSAvoiddetection specificity
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The amplification primers are designed with specific local sequences that match only CYP2C9 gene regions containing polymorphic sites. This localized specificity ensures high amplification efficiency for target sequences while preventing amplification of similar CYP2C19 sequences, resolving the contradiction between productivity and measurement precision

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The invention creates specific copies of CYP2C9 gene regions through targeted amplification using sequence-specific primers. This selective copying approach ensures that only the desired CYP2C9 polymorphic regions are amplified with high efficiency, while excluding CYP2C19 sequences, thereby maintaining both productivity and detection specificity

Inventive Principle:
Principle #26Copying

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 allows for the rapid and reliable detection of clinically significant CYP2C9 polymorphisms, facilitating the selection of appropriate therapeutic agents and doses, thereby reducing the risk of adverse drug reactions and improving treatment outcomes.

Implementation Method 1

The present invention provides oligonucleotide sequences that can be used as amplification primers and detection probes to selectively detect and identify CYP2C9 single nucleotide polymorphisms (SNPs)

Methodology Applied
Scientific EffectNucleic acid hybridization:

Data Source

PatentEP2111465B1Reagents and methods for detecting CYP2c9 polymorphisms
Publication Date: 2013.12.04 SIEMENS HEALTHCARE DIAGNOSTICS INC
  • EP2111465B1 patent drawingFigure 1
  • EP2111465B1 patent drawingFigure 2
  • EP2111465B1 patent drawingFigure 3

AI summary

The present invention relates to oligonucleotide sequences for amplification primers and detection probes and their use in nucleic acid amplification methods for the specific detection of clinically relevant CYP2C9 polymorphisms, in particular CYP2C9 polymorphisms associated with adverse drug response. The oligonucleotide sequences are also provided assembled as kits that can be used to predict how an individual will respond to drugs or other xenobiotic compounds that are metabolized, at least in part, by CYP2C9.