Liquid Biopsy Cell-Free RNA Pharmacodynamic Profiling
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current liquid biopsy approaches primarily focus on drug clearance and metabolism, limiting their application in providing comprehensive diagnostic or prognostic intelligence for pharmacodynamic markers related to homeostasis, cellular functions, and disease progression, thereby hindering the advancement of precision medicine.
Innovation Solution
A method is developed to generate personalized pharmacodynamic profiles by isolating and analyzing cell-free RNA from liquid biopsies, normalizing the data using tissue-specific markers, and correlating RNA levels with protein abundance to identify relevant pharmacodynamic markers, enabling improved diagnostic and prognostic insights.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If liquid biopsy approaches focus on drug clearance and metabolism, then pharmacokinetic information can be obtained, but pharmacodynamic markers related to homeostasis, cellular functions, and disease progression cannot be identified
Solution Approach 1:
The patent applies universality by developing a liquid biopsy method that simultaneously provides both pharmacokinetic information (drug clearance and metabolism) and pharmacodynamic marker identification. The method uses a unified approach to analyze cell-free RNA for multiple purposes: determining drug-metabolizing enzyme levels for pharmacokinetics and identifying pharmacodynamic markers for homeostasis, cellular functions, and disease progression, thereby making the liquid biopsy technique multi-functional and broadly applicable
2Measurement precision
If cell-free RNA levels are used to determine protein abundance, then pharmacodynamic markers can be identified, but shedding variability between individuals must be corrected
Solution Approach 1:
The patent uses tissue-specific marker genes as intermediaries to correct for shedding variability. These markers serve as reference points that allow the method to distinguish between variations in RNA shedding and actual variations in protein abundance. By normalizing target gene expression levels against tissue-specific marker levels, the method achieves accurate protein abundance determination while accounting for individual shedding differences
3Ease of operation
If liquid biopsy is used for genotyping tumours, then invasive solid tissue biopsy can be avoided, but pharmacodynamic profiling for precision medicine cannot be achieved
Solution Approach 1:
The patent extends the utility of liquid biopsy beyond genotyping to include comprehensive pharmacodynamic profiling. The same cell-free RNA sample used for tumour genotyping can simultaneously provide pharmacodynamic marker information related to homeostasis, cellular functions, and disease progression. This multi-functional application maintains the non-invasive advantage while eliminating the information loss that would otherwise require additional invasive procedures
Data Source
AI summary
Methods and systems for generating a personalised pharmacodynamic profiles for an individual subject are provided. The method comprises the steps of: isolating total cell free RNA (cfRNATOTAL) from a liquid biopsy obtained from the individual subject and identifying an amount of at least a first cell free RNA (cfRNA) present in the liquid biopsy, wherein the first cfRNA encodes a first protein that has a pharmacodynamic activity. From the amount of cfRNA in the liquid biopsy an amount of the first protein in the individual subject can be determined, thereby allowing a personalised pharmacodynamic profile for the individual subject to be generated. The methods and systems find utility in precision dosing and personalised medicine.