Engineered Bacteria for Non-Invasive Gut Diagnostics

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Solution Overview

Problem

Current methods lack non-destructive and non-invasive strategies to interrogate the gut microbiome, which is crucial for diagnosing and treating gastrointestinal tract conditions such as colorectal cancer and inflammatory bowel disease.

Innovation Solution

Genetic engineered Escherichia coli bacteria with genome-integrated genetic memory circuits that can sense specific environmental conditions in the gut long after the initial stimulus, allowing for diagnostic and therapeutic applications without invasive procedures.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If invasive procedures like endoscopy and colonoscopy are used to interrogate the gut, then measurement precision is improved, but object-generated harmful factors increase due to patient discomfort and potential tissue damage

Engineering Contradiction:

Improvediagnostic accuracyVSAvoidpatient harm

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent uses engineered bacteria as intermediary agents that reside in the gut and report environmental conditions back to external detectors. These bacteria express reporter proteins (fluorescent proteins, enzymes) that can be non-invasively detected, serving as a mediator between the internal gut environment and external diagnostic tools, thereby eliminating the need for invasive procedures while maintaining diagnostic capability

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces mechanical invasive procedures (endoscopy, colonoscopy) with a biochemical detection system. Instead of physically inserting instruments into the gut, the system uses genetically engineered bacteria that convert environmental signals into detectable biochemical signals (fluorescence, enzyme activity) that can be measured externally, substituting mechanical intrusion with molecular reporting

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Ease of operation

If genetic engineered bacteria with memory circuits are used to sense gut conditions, then ease of operation is improved, but device complexity increases due to the sophisticated genetic circuits

Engineering Contradiction:

Improvediagnostic convenienceVSAvoidgenetic circuit complexity

Core Design Contradiction:

Ease of operationVSDevice complexity

Solution Approach 1:

The genetic circuit is divided into separate functional modules: trigger elements that sense specific environmental conditions (pH, antibiotics, metabolites), memory elements that record the sensing event through bistable state transitions, and reporter elements that express detectable proteins. This modular segmentation allows each component to be optimized independently and simplifies the overall system design and construction

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The bacteria are pre-engineered with integrated memory circuits before administration to the patient. The genetic circuits are constructed and validated in vitro, then the engineered bacteria are introduced to the gut environment already equipped with their sensing and reporting capabilities, eliminating the need for complex in vivo circuit assembly or real-time programming

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS10907221B2Engineered genetic enteric sensor bacteria and uses thereof

Publication Date: 2021.02.02 PRESIDENT & FELLOWS OF HARVARD COLLEGE

AI summary

The disclosure relates to genetic engineered bacteria having a genetic memory circuit, compositions thereof, formulations thereof, methods of analyses and method of treatment of conditions related to the gastrointestinal tract including the mouth and the stomach.