Cell-Free RNA Biomarker Panels for Accurate Trisomy 21 Detection
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Solution Overview
Problem
Current non-invasive prenatal screening methods for trisomy 21, such as NIPS, suffer from inaccuracies due to undetected multiple fetuses, incorrect pregnancy dating, normal variation in ultrasound measurements, and maternal protein levels, leading to a significant chance of false positives and the need for invasive confirmatory tests like amniocentesis, which carry a risk of miscarriage.
Innovation Solution
The use of a combination of nucleic acid biomarkers, including ATP5O, ICOSLG, DOP1B, PKNOX1, COL6A1, and GART, detected through hybridization with complementary primers or probes in cell-free nucleic acids from maternal plasma, to accurately identify trisomy 21 by measuring altered expression levels in a statistically significant manner.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If non-invasive prenatal screening methods (NIPS) are used to detect trisomy 21, then the risk of miscarriage is reduced, but the measurement precision and reliability deteriorate due to false positives from undetected multiple fetuses, incorrect pregnancy dating, and normal variation in ultrasound measurements
Solution Approach 1:
The patent segments the detection process into multiple independent measurement components: cell-free DNA fragment size distribution analysis, protein biomarker measurement, and ultrasound dating. By analyzing multiple separate parameters and integrating their results, the method reduces false positives from any single measurement error source while maintaining non-invasive safety.
Solution Approach 2:
The patent changes the measurement parameters from traditional single-marker approaches to multi-parameter analysis including DNA fragment size distribution (using different size thresholds), multiple protein biomarkers, and ultrasound measurements. This multi-parameter approach allows statistical integration that improves detection accuracy while keeping the non-invasive benefit.
2Device complexity
If traditional screening methods with single biomarkers are used, then the device complexity is low, but the reliability and detection rate deteriorate due to significant false positive rates requiring invasive confirmatory tests
Solution Approach 1:
The patent merges multiple previously separate screening approaches into a single integrated non-invasive method: combining cell-free DNA fragment size analysis with protein biomarker measurement and ultrasound dating. This merging creates a unified screening system that improves reliability through multi-parameter statistical integration while maintaining relative simplicity through a single blood draw and standardized protocol.
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 significantly reduces false positives and negatives, providing a high detection rate for trisomy 21 with a low risk of miscarriage by offering a non-invasive method that can reliably differentiate between normal and trisomy 21 fetuses.
Implementation Method 1
the detecting comprises: contacting the cell free nucleic acids with primers or probes that are complementary to the nucleic acid biomarkers in the combination of nucleic acid biomarkers, and detecting hybridization between the primers or probes and the combination of nucleic acid biomarkers
Data Source
AI summary
Methods for detecting a Group of Biomarkers is provided herein. The translation profile of the Group of Biomarkers can be used for determining whether a subject, such as a fetus, has Down syndrome The methods include detecting one or more specific groups of biomarkers in a biological sample, and determining whether the expression of the biomarkers is altered when compared to expression of the biomarkers in one or more subjects that do not have trisomy 21 (e.g., a transcriptional standard). The biological sample can be a blood sample, and the biomarkers are cell free plasma RNAs.