Cell-Free RNA Liquid Biopsy for Cell Type Profiling

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Solution Overview

Problem

Current methods for evaluating cell types in human biological samples, such as blood or urine, primarily focus on tissue-level contributions and lack insight into cellular pathophysiology, which is crucial for understanding disease origins and progression.

Innovation Solution

A method involving the detection of cell-free RNA (cfRNA) from specific indicative genes in biological samples to generate scores that reflect the status of cell types, allowing for comparison to control values or prior scores, enabling non-invasive evaluation and treatment monitoring of conditions like kidney or brain function.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If tissue-level cfRNA analysis is performed, then broad clinical utility is achieved, but cellular pathophysiology insight is lost

Engineering Contradiction:
Improveclinical utilityVSAvoidcellular pathophysiology insight
Core Design Contradiction:
Adaptability or versatilityVSLoss of information

Solution Approach 1:

The patent segments the tissue-level cfRNA analysis into cell type-specific analyses by identifying and measuring cfRNA from different cell types (e.g., hepatocytes, cardiomyocytes, neurons) separately. This segmentation allows the method to maintain broad clinical utility while recovering cellular pathophysiology insight that was previously lost in aggregate tissue analysis.

Inventive Principle:
Principle #1Segmentation

2Loss of information

If cell type-specific cfRNA detection is implemented, then cellular pathophysiology insight is improved, but assay complexity increases

Engineering Contradiction:
Improvecellular pathophysiology insightVSAvoidassay complexity
Core Design Contradiction:
Loss of informationVSDevice complexity

Solution Approach 1:

The patent employs a universal panel of cell type-specific gene markers that can be used across multiple disease contexts and biological samples. This multi-functional approach allows a single assay design to detect cfRNA from various cell types (liver, heart, brain, kidney, etc.) without requiring separate complex assays for each cell type, thereby reducing overall assay complexity while maintaining cellular resolution.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Measurement precision

If invasive biopsy is performed, then cellular resolution is achieved, but patient risk and invasiveness increase

Engineering Contradiction:
Improvecellular resolutionVSAvoidpatient risk
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent uses cell-free RNA in blood plasma as an intermediary that carries molecular information from internal tissues and cells without requiring direct physical access to those tissues. This intermediary approach allows cellular-resolution monitoring of tissue health and disease states through simple blood draws, eliminating the need for invasive biopsies while maintaining measurement precision.

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentUS20240191300A1Profiling cell types in circulating nucleic acid liquid biopsy
Publication Date: 2024.06.13 CHAN ZUCKERBERG BIOHUB INC
  • US20240191300A1 patent drawing
  • US20240191300A1 patent drawing
  • US20240191300A1 patent drawing

AI summary

Methods and compositions for detecting specific cell types using cell-free RNA (cfRNA) are provided. In some embodiments, methods of evaluating tissue or organ function and methods of treatment are provided comprising detecting specific cell types using cfRNA.