Genetically Engineered Bacteria Delivering 3-HB for Gut Inflammation
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Solution Overview
Problem
Current treatments for inflammatory diseases, particularly those affecting the intestinal tract like inflammatory bowel disease (IBD) and colorectal cancer, fail to effectively suppress the underlying inflammatory process and often have side effects, requiring new therapeutics that can target inflammation locally and have fewer adverse effects.
Innovation Solution
The use of 3-hydroxybutyric acid (3-HB) or its salts, delivered via genetically engineered anaerobic bacteria, which produce (R)-3-HB, to modulate gut flora and reduce pro-inflammatory cytokines while increasing anti-inflammatory cytokines, thereby addressing inflammation in the gastrointestinal tract.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If traditional drug therapies (aminosalicylates and steroids) are used to treat inflammatory diseases, then symptomatic improvement is provided, but the underlying inflammatory process is not stopped and the disease course is not changed
Solution Approach 1:
The invention changes the chemical parameter from conventional drugs to 3-hydroxybutyric acid (3-HB), a metabolite that naturally modulates inflammation. 3-HB works by altering the metabolic and inflammatory parameters at the cellular level, providing both symptomatic relief and disease-modifying effects by suppressing the underlying inflammatory process without the side effects of traditional therapies
Solution Approach 2:
The invention uses genetically engineered anaerobic bacteria as intermediaries to deliver 3-HB directly to the site of inflammation in the gastrointestinal tract. These bacteria serve as a mediator that produces and releases 3-HB locally, ensuring targeted therapy while minimizing systemic exposure and side effects
2Adaptability or versatility
If biological agents (antibodies) are used to target inflammatory cytokines, then alternative treatment options are provided, but they require systemic administration and may have limited local efficacy
Solution Approach 1:
Genetically engineered anaerobic bacteria serve as living intermediaries that are administered orally and colonize the gastrointestinal tract. These bacteria continuously produce and release 3-HB directly at the site of inflammation, achieving high local concentrations without requiring systemic administration, thereby overcoming the limitations of antibody-based therapies
Solution Approach 2:
The genetically engineered bacteria are designed to autonomously produce and secrete 3-HB once they colonize the gut. This self-service mechanism ensures continuous local delivery of the anti-inflammatory agent without requiring repeated external administration, maintaining therapeutic levels at the site of inflammation
3Ease of operation
If current treatments are used to manage inflammatory diseases, then patient compliance is maintained, but side effects occur and long-term efficacy is limited
Solution Approach 1:
The invention converts the natural metabolic process of anaerobic bacteria into a therapeutic benefit. By engineering bacteria to produce 3-HB, a naturally occurring metabolite, the treatment leverages the bacteria's metabolic capabilities to generate an anti-inflammatory agent that acts locally in the gut, converting what could be a source of harm (bacterial presence) into a beneficial therapeutic effect with minimal side 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
3-HB effectively downregulates pro-inflammatory cytokines and upregulates anti-inflammatory cytokines, providing a broader therapeutic effect compared to traditional biological agents, with improved safety and compliance, and can be delivered locally to the site of inflammation in the GI tract.
Implementation Method 1
genetically engineered anaerobic bacteria, which produce (R)-3-HB
Data Source
AI summary
The invention relates to compositions and uses thereof in methods for treating an inflammatory disease, disorder or condition in a subject, in particular an inflammatory disease, disorder or condition of the digestive tract such as inflammatory bowel disease (IBD) and/or colorectal cancer. The invention also relates to probiotic compositions and the use of the compositions for treating gastrointestinal disorders.