Engineered Bacteria for Ammonia Conversion in Liver Disease
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Solution Overview
Problem
Current therapies for hepatic encephalopathy, non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), and other liver disorders associated with elevated liver inflammation and hyperammonemia are insufficient, leading to a significant unmet need for effective, reliable, and long-term treatments.
Innovation Solution
Genetically engineered bacteria are developed to reduce excess ammonia and inflammation by converting ammonia into alternate byproducts, such as arginine, and are administered to the gut to treat liver diseases, including hepatic encephalopathy, NASH, NAFLD, and other conditions by modulating gene sequences encoding ammonia consumption and arginine production circuits, and are designed to be non-pathogenic and probiotic.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used for hepatic encephalopathy and liver diseases, then treatment is provided, but the treatment is insufficient and does not meet the need for effective, reliable, and long-term solutions
Solution Approach 1:
The patent uses genetically engineered bacteria as an intermediary organism to treat liver diseases. These bacteria are designed to consume ammonia and produce anti-inflammatory compounds, acting as a biological mediator between the patient's metabolic system and the therapeutic outcome. The bacteria serve as a living drug delivery system that continuously performs therapeutic functions within the gut-liver axis.
Solution Approach 2:
The engineered bacteria are designed to autonomously perform therapeutic functions by consuming ammonia through their metabolic pathways and producing beneficial compounds. The bacteria self-regulate their ammonia consumption and compound production based on environmental conditions, providing continuous self-sustaining treatment without requiring external intervention for drug administration.
2Object-affected harmful factors
If ammonia levels are reduced through conventional methods, then hyperammonemia is treated, but inflammation and liver damage are not adequately addressed
Solution Approach 1:
The patent combines multiple therapeutic functions into a single engineered bacterial system. The bacteria simultaneously perform ammonia consumption, anti-inflammatory compound production, and gut barrier protection. This merging of functions addresses multiple pathological aspects (hyperammonemia, inflammation, gut permeability) through one integrated therapeutic agent rather than separate treatments.
Solution Approach 2:
The engineered bacteria are designed with multi-functionality to address various aspects of liver disease pathology. They can consume ammonia, produce anti-inflammatory compounds, strengthen gut barrier function, and modulate the gut-liver axis. This universal approach allows a single therapeutic agent to tackle multiple disease mechanisms simultaneously.
3Stability of the object's composition
If probiotics are used to improve gut barrier function, then intestinal permeability is reduced, but ammonia consumption and inflammation reduction are not sufficiently addressed
Solution Approach 1:
The engineered bacteria serve as a biological intermediary that connects gut barrier function improvement with ammonia removal and inflammation reduction. Through their metabolic activities, they mediate between the gut environment and liver health, transforming ammonia into beneficial compounds while simultaneously strengthening gut barrier function through anti-inflammatory effects.
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 genetically engineered bacteria effectively reduce inflammation and ammonia levels in the liver and gut, decreasing IL-6, TNFα, TGFβ, and αSMA gene expression, and ammonia levels, thereby treating liver diseases and preventing liver damage and fibrosis.
Implementation Method 1
capable of reducing excess ammonia and converting ammonia and/or nitrogen into alternate byproducts
Implementation Method 2
modulating gene sequences encoding ammonia consumption and arginine production circuits
Data Source
AI summary
The disclosure provides genetically engineered bacteria that are capable of reducing excess ammonia and converting ammonia and/or nitrogen into alternate byproducts. The invention also provides pharmaceutical compositions comprising the genetically engineered bacteria, and methods of modulating and treating disorders associated with excess ammonia and inflammation in the gut and the liver, including, for example, hepatic encephalopathy, NASH/NAFLD, HCV, and Huntington's disease, in a subject, comprising administering the engineered bacterium to the subject.