Apheresis Device for Extracorporeal cfDNA Removal
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Solution Overview
Problem
Current methods for reducing circulating cell-free DNA (cfDNA) levels in the body, such as systemic administration of deoxyribonuclease enzymes, have shown limited effectiveness in clinical settings, and there is a need for new technologies to address diseases associated with high cfDNA levels and improve organ transplantation outcomes.
Innovation Solution
A device configured for apheresis using one or more affinity matrices capable of capturing nucleosome-bound, exosome-bound, and unbound cfDNA, incorporating DNA binding proteins, antibodies, and intercalating agents, which are integrated into an extracorporeal organ perfusion circuit to reduce cfDNA levels in organ perfusion solutions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If systemic deoxyribonuclease enzymes are administered to reduce circulating cfDNA levels, then cfDNA degradation is achieved, but treatment effectiveness is limited in clinical settings
Solution Approach 1:
The patent extracts and removes cfDNA from the circulation system using affinity matrices that specifically bind and capture cfDNA molecules, separating them from the blood plasma. This extraction approach directly removes the harmful substance rather than relying on enzymatic degradation, achieving more effective cfDNA reduction in clinical settings.
Solution Approach 2:
The patent introduces affinity matrices as intermediary substances that mediate the removal of cfDNA. These matrices contain binding sites that specifically interact with cfDNA, facilitating its capture and removal from circulation. The affinity matrices act as intermediaries between the blood plasma and the removal system, enabling efficient cfDNA extraction.
2Reliability
If affinity matrices with multiple binding mechanisms are used to capture all types of cfDNA, then cfDNA removal effectiveness is improved, but device complexity increases
Solution Approach 1:
The patent combines multiple affinity matrices with different binding mechanisms (histone-protein interactions, DNA-protein interactions, DNA-DNA hybridization) into a single integrated apheresis device. This merging of multiple capture mechanisms allows the device to effectively remove all types of cfDNA (nucleosome-bound, exosome-bound, and unbound) while maintaining a unified device structure.
Solution Approach 2:
The apheresis device is designed with multi-functional affinity matrices that can capture different types of cfDNA through various binding mechanisms. The device universally handles nucleosome-bound cfDNA, exosome-bound cfDNA, and unbound cfDNA, making it applicable to all cfDNA-related pathological conditions without requiring multiple separate devices.
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
The device effectively captures and reduces all types of cfDNA, including nucleosome-bound, exosome-bound, and unbound forms, thereby improving organ quality and reducing unfavorable transplantation outcomes like transplant dysfunction and graft rejection.
Implementation Method 1
one or more affinity matrices capable of capturing one or more cell free DNA (cfDNA) selected from nucleosome-bound cfDNA, exosome-bound cfDNA, and unbound cfDNA from the organ perfusion solution
Data Source
AI summary
The invention provides apheresis devices and their use for substantial removal of all types of cfDNA for treatment of various diseases and during perfusion of an organ and/or anatomical cavity, to limit the negative effects of circulating cfDNA during organ transplantation and thus improve the quality and survival of transplanted organs, and reduce unfavorable transplantation outcomes such as transplant dysfunction, ischemia-reperfusion injury, graft rejection, and organ failure.