Engineered Bacteria Biosensors for Precision Targeting
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Solution Overview
Problem
Current bacterial therapies face challenges in precisely controlling bacterial growth at specific disease sites, leading to uncontrolled replication and severe side effects, and lack precise confinement to intended organs, which is crucial for effective treatment and safety.
Innovation Solution
Engineered non-pathogenic bacteria equipped with inducible promoters responsive to specific environmental or physiological conditions, such as hypoxia, lactate, and pH, allowing for controlled expression of essential genes and targeted growth in specific organs or tumors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If natural tropism of bacteria is used for targeting organs, then bacteria can colonize target organs, but bacteria cannot be precisely confined to specific disease sites and spread to unintended locations
Solution Approach 1:
The patent changes the physiological parameters (oxygen concentration, pH, lactate levels) that control bacterial growth. By engineering bacteria with promoters that respond to specific combinations of these parameters, the bacteria can distinguish between different tissue microenvironments and colonize only the intended target site with the correct parameter profile, preventing off-target colonization.
Solution Approach 2:
The patent implements feedback control through biosensors that continuously monitor local physiological conditions. The bacteria sense their environment and adjust their growth rate accordingly - growing only when the sensor detects the specific parameter combination characteristic of the target disease site, and inhibiting growth when encountering unintended locations with different physiological parameters.
2Productivity
If bacterial growth is allowed to replicate quickly at disease sites, then treatment efficacy is improved, but uncontrolled growth leads to severe side effects including tissue damage and septic shock
Solution Approach 1:
The patent uses parameter changes by coupling essential gene expression to promoters that respond to specific physiological parameter combinations found only at the disease site. This ensures rapid bacterial replication and high treatment efficacy only when the correct parameters are present, while preventing uncontrolled growth and side effects in tissues with different parameter profiles.
Solution Approach 2:
The patent applies local quality by making bacterial growth rate location-specific through engineered biosensors. Each tissue type has unique physiological parameters, and the bacteria are designed to sense and respond to these local conditions, enabling fast growth only in the specific location where the disease is present, while maintaining slow or no growth elsewhere to avoid harmful side effects.
3Manufacturing precision
If inducible promoters responsive to multiple physiological conditions are used, then precise confinement to specific organs is achieved, but device complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the confinement control into multiple independent biosensor modules, each responsive to a single physiological parameter (oxygen, pH, lactate). These modular sensor-gene circuits can be independently designed and combined, allowing precise confinement through logical combinations of simple sensors rather than requiring a single complex sensing system.
Solution Approach 2:
The patent merges multiple simple biosensor systems into an integrated genetic circuit that responds to combinations of physiological parameters. By combining several single-parameter sensors with logical AND gates, the system achieves high confinement precision requiring all specified conditions to be met simultaneously, while keeping each individual sensor component relatively simple and well-characterized.
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 engineered bacteria demonstrate enhanced specificity and containment within targeted tissues, reducing off-target colonization and improving the safety and efficacy of bacterial therapies by using biosensors to regulate growth in response to physiological cues.
Implementation Method 1
the inducible promoter is induced by an external or exogenous agent... This type of inducible promoter includes but is not limited to hypoxia-sensing promoters
Implementation Method 2
the inducible promoter is induced by an external or exogenous agent... pH sensing promoters
Implementation Method 3
the inducible promoter is induced by an external or exogenous agent... lactate sensing promoters
Data Source
AI summary
The disclosure herein relates to engineered biosensor-containing bacteria, which is bacteria that contain at least one biosensor circuit, and uses thereof. A biosensor circuit can comprise an essential gene of the bacteria operably linked to an inducible promoter. Additionally, the bacteria can be engineered to be deficient in the endogenous copy of the at least one essential gene.