UGT1A1 Polymorphism Detection via Nucleic Acid Probe Hybridization
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Solution Overview
Problem
Conventional methods for detecting UGT1A1 polymorphisms associated with irinotecan toxicity lack sufficient detection accuracy and are not cost-effective.
Innovation Solution
A hybridization method using nucleic acid probes targeting specific sequences within the TATA box region of the UGT1A1 gene to determine the ratio of hybridized nucleic acids, allowing for accurate prediction of adverse effects by measuring the ratio of nucleic acids hybridized to different probe pairs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional methods (direct sequencing, fragment analysis, Invader assay) are used to detect UGT1A1 polymorphisms, then detection can be performed, but detection accuracy is insufficient and cost-effectiveness is poor
Solution Approach 1:
The detection method is segmented into distinct functional components: specific primers for PCR amplification of the TATA box region, fluorescently labeled nucleic acid probes for hybridization detection, and ratio-based quantification. This segmentation allows each component to be optimized independently, achieving high detection accuracy through precise probe-design while maintaining cost-effectiveness by using standard PCR and hybridization technologies rather than complex sequencing infrastructure
Solution Approach 2:
The invention changes the detection parameter from qualitative/semi-quantitative methods to a quantitative ratio-based measurement system. By measuring the ratio of fluorescent signals from different probe hybridizations and comparing it to reference ratios, the method achieves high detection accuracy and objectivity. This parameter transformation enables precise polymorphism detection while using cost-effective standard laboratory equipment
2Reliability
If conventional detection methods are used, then polymorphism detection can be performed, but the methods are not cost-effective
Solution Approach 1:
The method uses nucleic acid probe hybridization to create a detectable copy signal of the polymorphism without requiring full sequencing. The fluorescently labeled probes bind to the amplified TATA box region, and the hybridization signal ratio provides reliable polymorphism identification. This copying approach achieves detection reliability comparable to sequencing while using far less expensive reagents and equipment
Solution Approach 2:
The invention replaces complex mechanical/chemical sequencing processes with a simpler hybridization-based detection system. Instead of using sophisticated sequencing machinery and complex biochemical reactions, the method uses standard PCR followed by probe hybridization and fluorescent detection. This substitution maintains detection reliability while dramatically reducing costs by using off-the-shelf PCR and hybridization reagents
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 method provides a simple and efficient means to detect UGT1A1 polymorphisms with high accuracy, enabling the prediction of irinotecan-related adverse effects and improving patient risk assessment.
Implementation Method 1
a hybridization method, using nucleic acid probes wherein each of the nucleic acid probes comprises either a nucleotide sequence of 25 to 35 contiguous nucleotides including the TATA box within the promoter region of the UDP-glucuronosyl transferase gene
Data Source
AI summary
A method for determining the risk of adverse effects of irinotecan (CPT-11), a synthetic anticancer drug, by detecting polymorphisms in the TATA box within the promoter region of the UDP-glucuronosyl transferase gene. A kit for detecting the adverse effects of irinotecan containing at least one pair of nucleic acid probes.