PAP DNA Marker Detection for Early Transplant Failure
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for detecting organ transplantation failure, such as PCR-based technologies, face challenges with false positives and false negatives, and are unable to detect early stages of transplant rejection effectively due to low sensitivity and selectivity.
Innovation Solution
The use of ultra-high sensitive pyrophosphorolysis-activated polymerization (PAP) technology to detect single copies of donor-positive but recipient-negative DNA markers in the recipient's plasma, allowing for early detection of transplantation failure through a universal set of PAP assays applicable to various transplantations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If PCR-based methods are used to detect DNA markers, then the detection can be performed with standard technology, but the sensitivity is insufficient to detect single copy mutations and produces false positives and false negatives
Solution Approach 1:
The patent changes the fundamental detection parameters by using PAP technology instead of PCR. PAP achieves single-copy detection sensitivity through its unique pyrophosphorolysis-activated polymerization mechanism, which provides over 1,000,000 times better selectivity and 100 times better sensitivity compared to PCR-based methods, thereby resolving the contradiction between detection sensitivity and false positive rate.
2Measurement precision
If standard PCR technology is used, then the detection process is relatively simple, but it cannot detect very early stage transplant rejection due to low sensitivity
Solution Approach 1:
The patent replaces the PCR mechanical amplification system with the PAP system. PAP uses pyrophosphorolysis to remove blocking groups from primers only when they are perfectly matched to the target sequence, providing intrinsic selectivity without requiring complex nested PCR protocols or multiple amplification steps, thus achieving early detection with manageable complexity.
3Measurement precision
If individualized DNA markers are selected for each donor-recipient pair, then detection accuracy is maximized, but the cost and complexity of monitoring increases significantly
Solution Approach 1:
The patent develops universal PAP assays that can detect donor-specific DNA markers across different transplantation types (kidney, liver, heart, lung, islet cell, bone marrow). This universal approach maintains high detection accuracy by identifying polymorphic markers specific to each donor-recipient pair while using the same PAP technology platform, thereby reducing overall monitoring costs and simplifying the detection process.
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 enables the detection of transplantation failure at very early stages with high sensitivity and selectivity, reducing costs and invasive testing, and facilitating timely intervention with conventional rejection therapy.
Implementation Method 1
ultra-high sensitive pyrophosphorolysis activated polymerization (PAP) is used to detect even a single copy of donor-positive but recipient-negative DNA markers in recipient blood
Data Source
AI summary
The present invention provides a method for detecting transplantation failure of a transplanted organ or cells which comprises detecting a donor-positive but recipient-negative DNA marker in the recipient's plasma using pyrophosphorolysis activated polymerization. Because of the high sensitivity, specificity and selectivity of pyrophosphorolysis activated polymerization, transplantation failure can be detected at early stages and treatment can be initiate earlier.