Engineered Microorganisms for Non-Invasive Gastrointestinal Disease Detection
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Solution Overview
Problem
Current diagnostic methods for gastrointestinal diseases, such as colonoscopies, are invasive and uncomfortable for patients, and often fail to detect early or flat abnormal cells effectively, particularly in individuals with a genetic predisposition to gastrointestinal cancers.
Innovation Solution
A genetically engineered microorganism is administered to the gastrointestinal tract to direct the expression of a secretable biomarker in diseased cells, which is then detected in biological samples like urine, saliva, or blood, avoiding invasive procedures by targeting specific cell membrane receptors exposed on diseased epithelial cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If endoscopy or colonoscopy is used to diagnose gastrointestinal diseases, then diagnostic accuracy is improved, but patient comfort and ease of operation deteriorate due to invasive procedures
Solution Approach 1:
A genetically engineered microorganism acts as an intermediary carrier to deliver a nucleic acid encoding a secretable biomarker to diseased epithelial cells in the gastrointestinal tract. The microorganism specifically targets and binds to receptors on diseased cells, enabling non-invasive detection through biomarker secretion into body fluids, thus resolving the contradiction between diagnostic accuracy and patient comfort
Solution Approach 2:
The patent replaces the mechanical invasive procedure of endoscopy/colonoscopy with a biological detection system. Instead of physically inserting instruments into the gastrointestinal tract, the system uses engineered microorganisms that naturally navigate the GI tract and deliver genetic material, with detection performed through non-invasive collection of body fluids containing the secretable biomarker
2Measurement precision
If endoscopy or colonoscopy is used to detect early or flat abnormal cells, then detection capability is improved, but the procedure complexity and patient burden increase
Solution Approach 1:
The genetically engineered microorganism serves as a mediator that specifically targets diseased epithelial cells by binding to cell membrane receptors exposed on the luminal side of diseased cells. This specific targeting capability enables early detection of abnormal cells without requiring complex invasive procedures, as the microorganism naturally navigates to and interacts with the target cells
Solution Approach 2:
The microorganism delivers a copy of the nucleic acid encoding the secretable biomarker to the diseased cells. The diseased cells then produce and secrete the biomarker, creating a detectable signal that copies the presence of the disease state, enabling early detection through simple biomarker measurement in body fluids
3Reliability
If invasive procedures like colonoscopy are used for monitoring, then disease detection reliability is improved, but loss of time and patient burden increase
Solution Approach 1:
The engineered microorganism enables continuous monitoring capability by establishing a persistent presence in the gastrointestinal tract. The microorganism continuously delivers the nucleic acid encoding the secretable biomarker to diseased cells, allowing for repeated non-invasive detection through body fluid sampling, thus maintaining reliable disease detection while eliminating the need for repeated invasive procedures
Solution Approach 2:
The patent substitutes the time-consuming, resource-intensive mechanical process of repeated colonoscopies with a simplified biological monitoring system. The engineered microorganism performs the detection function continuously, and results are obtained through rapid biomarker measurement in body fluids, significantly reducing the time and patient burden associated with monitoring
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 allows for non-invasive detection of diseased epithelial cells, including precancerous lesions and cancers, by measuring the biomarker in easily obtainable biological fluids, facilitating early detection and monitoring of gastrointestinal diseases.
Implementation Method 1
a genetically engineered microorganism that directs expression of a secretable biomarker specifically in diseased cells
Implementation Method 2
The microorganism comprises a gene encoding a surface protein that specifically interacts with one or more cell membrane receptor(s) that are exposed to the luminal side of epithelial cells of diseased gastrointestinal tissue
Data Source
AI summary
The present invention relates to, inter alia, engineered microorganisms expressing (i) a surface protein, which specifically interacts cell membrane receptors that are specifically exposed to the luminal side of epithelial cells of diseased gastrointestinal tissue, and (ii) a secretable biomarker. The engineered bacteria of the present technology are useful for detecting diseased gastrointestinal tissue.