Linker Histone Complexes for cfDNA Subtype Isolation
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Solution Overview
Problem
Current methods for isolating and analyzing cell-free DNA (cfDNA) from biological samples are not sensitive, robust, or versatile enough for effective detection and monitoring of diseases, particularly in identifying various subtypes of cfDNA that contribute to disease progression.
Innovation Solution
A method involving the use of linker histones to form complexes with cfDNA, followed by separation and release, which can include immobilization on solid supports, use of proteases for purification, and analysis through DNA sequencing or PCR, allowing for the detection and treatment of diseases characterized by elevated cfDNA levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional cfDNA isolation methods are used, then the process is simple, but the sensitivity and robustness are insufficient for detecting various subtypes of cfDNA
Solution Approach 1:
The invention segments cfDNA into distinct subtypes (nucleosome-bound, exosome-bound, and unbound cfDNA) and develops specific isolation methods for each subtype. This segmentation enables sensitive detection of individual cfDNA populations while maintaining a systematic approach to the overall isolation process.
Solution Approach 2:
The invention introduces specific binding agents as intermediaries to capture different cfDNA subtypes. These intermediaries enable selective isolation of each cfDNA population, enhancing detection sensitivity without requiring direct complex isolation procedures.
2Measurement precision
If comprehensive cfDNA analysis is performed to detect all subtypes, then the diagnostic accuracy improves, but the time and resources required increase
Solution Approach 1:
The invention performs preliminary classification and isolation of different cfDNA subtypes before final analysis. By pre-separating nucleosome-bound, exosome-bound, and unbound cfDNA, the method streamlines subsequent diagnostic analysis, reducing overall analysis time while maintaining comprehensive diagnostic accuracy.
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 enhances the sensitivity and robustness of cfDNA isolation and analysis, enabling more accurate detection and monitoring of diseases, including cancer, by capturing and analyzing nucleosome-bound, exosome-bound, and unbound cfDNA, thereby guiding therapeutic decisions.
Implementation Method 1
contacting the biological sample with a linker histone, wherein the linker histone forms a complex with the cfDNA
Implementation Method 2
the linker histone is bound to a magnetic particle
Data Source
AI summary
The invention provides methods of detecting substantially all types of cell free DNA (cfDNA) in biological samples, including nucleosome-bound cfDNA, exosome-bound cfDNA and unbound cfDNA (including double stranded DNA (dsDNA), single stranded DNA (ssDNA) and oligonucleotides), for diagnosis, monitoring and treatment of diseases caused by, or correlated with, increased levels of cfDNA.