Fetal Nucleic Acid Enrichment via Methylation-Specific Binding
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Solution Overview
Problem
Current invasive prenatal diagnostic methods, such as chorionic villus sampling and amniocentesis, pose risks to both mother and fetus, and existing non-invasive methods are limited in sensitivity and applicability, particularly for female fetuses and diverse ethnic populations.
Innovation Solution
The development of human epigenetic biomarkers that utilize differential methylation patterns between fetal and maternal nucleic acids to enrich and quantify fetal nucleic acids in maternal samples, allowing for accurate detection and analysis of fetal genetic traits, including chromosomal abnormalities, through methylation-specific binding proteins and enzymes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If invasive procedures such as chorionic villus sampling or amniocentesis are used for prenatal diagnosis, then diagnostic accuracy is improved, but risk to mother and fetus increases
Solution Approach 1:
The patent extracts and analyzes cell-free fetal DNA circulating in maternal plasma as a non-invasive alternative to invasive procedures. By isolating and detecting fetal-specific DNA sequences from maternal blood samples, the method achieves diagnostic accuracy without the physical risks of chorionic villus sampling or amniocentesis
Solution Approach 2:
The patent uses cell-free fetal DNA in maternal plasma as an intermediary marker to indirectly assess fetal genetic conditions. This intermediary approach allows diagnosis without direct sampling of fetal tissues, eliminating the need for invasive procedures while maintaining diagnostic capability
2Object-affected harmful factors
If non-invasive methods detecting fetal DNA in maternal plasma are used, then risk to mother and fetus is reduced, but sensitivity and applicability worsen
Solution Approach 1:
The patent applies local quality by targeting specific differentially methylated regions (DMRs) with known methylation patterns unique to fetal versus maternal DNA. By focusing analysis on these specific loci rather than the entire genome, the method enhances sensitivity and applicability while maintaining non-invasive status
Solution Approach 2:
The patent exploits parameter changes in DNA methylation status between fetal and maternal cells at specific genomic regions. By detecting these epigenetic parameter differences through bisulfite conversion and methylation-specific PCR, the method overcomes the limitation of low fetal DNA fraction in maternal plasma
3Ease of operation
If existing non-invasive methods are used, then invasiveness is reduced, but ability to detect fetal traits in diverse populations worsens
Solution Approach 1:
The patent achieves universality by selecting differentially methylated regions that are conserved across diverse ethnic populations. The method uses universal methylation markers rather than population-specific genetic polymorphisms, enabling ethnicity-independent fetal trait detection while maintaining non-invasive operation
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
Enables non-invasive, sensitive, and ethnicity-independent detection of fetal genetic traits and chromosomal abnormalities, improving prenatal diagnosis by distinguishing fetal DNA from maternal DNA based on methylation status, applicable to both male and female fetuses.
Implementation Method 1
differential methylation patterns between fetal and maternal nucleic acids
Implementation Method 2
binding a target nucleic acid, from a sample, and a control nucleic acid, from the sample, to a methylation-specific binding protein
Implementation Method 3
digesting or removing maternal nucleic acid based on the methylation status
Data Source
AI summary
Provided are compositions and processes that utilize genomic regions that are differentially methylated between a mother and her fetus to separate, isolate or enrich fetal nucleic acid from a maternal sample. The compositions and processes described herein are particularly useful for non-invasive prenatal diagnostics, including the detection of chromosomal aneuploidies.