Engineered Microbial Cells for Uric Acid Degradation in Gout Treatment

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Solution Overview

Problem

Current treatments for chronic refractory gout are limited, with existing therapies often ineffective in reducing serum uric acid levels and associated with adverse reactions, necessitating a more effective and safer approach to manage hyperuricemia.

Innovation Solution

Engineered microbial cells, such as fungal or bacterial cells, are developed to express uric acid degrading polypeptides like uricase and uric acid transporters, which can effectively reduce serum uric acid levels by degrading uric acid in the gastrointestinal tract, providing a longer-lasting and more effective treatment compared to traditional uricase therapies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional uricase therapies are used, then uric acid levels are reduced, but the duration of action is short and adverse reactions occur

Engineering Contradiction:

Improveeffectiveness in reducing uric acidVSAvoidduration of uricolytic activity

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent embeds the uricase enzyme and uric acid transporter within a microbial cell structure. The microbial cell acts as a nested container that protects the therapeutic enzymes while providing sustained release capabilities, thereby extending the duration of action compared to free uricase administration

Inventive Principle:

Principle #7Nested doll (Nesting)

Solution Approach 2:

The engineered microbial cells autonomously perform uric acid degradation through their expressed uricase and uric acid transporter proteins. The cells self-replicate and maintain therapeutic activity within the gastrointestinal tract, providing sustained action without requiring frequent external dosing

Inventive Principle:

Principle #25Self-service

2Reliability

If traditional uricase therapies are used, then uric acid is degraded, but adverse reactions occur

Engineering Contradiction:

Improveuric acid degradation efficacyVSAvoidadverse reactions

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The microbial cell serves as an intermediary vehicle that delivers the uricase enzyme to the target site. This intermediary approach protects the enzyme from premature degradation and reduces direct exposure of the patient's immune system to the therapeutic protein, thereby minimizing adverse reactions

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent uses probiotic microbial strains that are naturally present in or on the human body. By engineering these familiar organisms rather than introducing completely foreign proteins, the immune system is less likely to recognize them as threats, reducing the risk of adverse immune reactions

Inventive Principle:

Principle #26Copying

3Ease of manufacture

If xanthine oxidase inhibitors are used, then uric acid synthesis is blocked, but the treatment is ineffective for refractory gout

Engineering Contradiction:

Improvetreatment accessibilityVSAvoidefficacy in refractory cases

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent replaces the upstream inhibition approach (blocking uric acid synthesis via xanthine oxidase inhibition) with a downstream degradation approach (direct uric acid breakdown via uricase). This substitution of therapeutic mechanism provides efficacy in refractory cases where synthesis inhibition has failed

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention changes the therapeutic parameter from preventing uric acid production to actively degrading existing uric acid. This parameter change allows the treatment to work in refractory gout patients whose disease progression continues despite synthesis blockade

Inventive Principle:

Principle #35Parameter changes

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 microbial cells provide sustained uricolytic activity, effectively lowering serum uric acid levels and offering relief from gout symptoms with reduced adverse reactions, addressing the limitations of existing treatments for chronic refractory gout.

Implementation Method 1

engineered microbial cells that have been engineered to comprise a uric acid degrading polypeptide... expressing uric acid degrading polypeptides like uricase... effectively reduce serum uric acid levels by degrading uric acid

Methodology Applied

Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentUS20230042430A1Therapeutic Engineered Microbial Cell System and Methods for Treating Hyperuricemia and Gout

Publication Date: 2023.02.09 THERANEUTRICS LLC

AI summary

The present disclosure relates to engineered microbial cells that have been engineered to include a uricase, a uric acid transporter, or both a uricase and a uric acid transporter. The engineered microbial cells of the present disclosure are useful in degrading uric acid inside the engineered microbial cell. The engineered microbial cells of the present disclosure are useful in methods of treating hyperuricemia. The engineered microbial cells of the present disclosure are also useful in methods of treating gout, and in particular chronic refractory gout.