Nematode Model for Bacteriophage Efficacy Testing

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Solution Overview

Problem

Current methods for selecting bacteriophages with therapeutic potential are limited by reliance on in vitro testing, which fails to predict efficacy in vivo due to differences in bacterial physiology and environment between lab cultures and infected organisms, leading to ineffective phage treatments in eukaryotic organisms.

Innovation Solution

A method using Caenorhabditis elegans as a model organism to evaluate bacteriophage therapeutic efficacy by infecting nematodes with pathogenic bacteria and assessing phage treatment effects on survival and bacterial eradication, allowing for real-time monitoring and selection of effective phages that may require adaptation for specific strains.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If bacteriophages are tested using in vitro methods in laboratory media, then the testing process is simple and cost-effective, but the results fail to predict therapeutic efficacy in vivo due to differences in bacterial physiology and environment

Engineering Contradiction:
Improvetesting simplicityVSAvoidpredictive accuracy of therapeutic efficacy
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent introduces an in vivo testing model using infected organisms as an intermediary system between in vitro laboratory testing and clinical human/animal trials. This intermediate model allows evaluation of bacteriophage therapeutic efficacy in a living system that more closely mimics human physiology, thereby improving predictive accuracy while maintaining relative simplicity and cost-effectiveness compared to full clinical trials.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If bacteriophages are selected based on in vitro lytic efficacy, then the selection process is rapid and efficient, but the selected phages become ineffective when administered into eukaryotic organisms due to physiological differences

Engineering Contradiction:
Improvephage selection speedVSAvoidtherapeutic efficacy in eukaryotic organisms
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent implements preliminary in vivo testing of bacteriophages in infected model organisms before advancing to clinical trials. This preliminary action in an intermediate living system allows identification of phages that maintain therapeutic efficacy in physiological conditions, preventing waste of resources on phages that would be ineffective in clinical settings while preserving the efficiency of rapid screening for promising candidates.

Inventive Principle:
Principle #10Preliminary action

3Reliability

If animal infection tests are conducted to evaluate phage therapy efficacy, then accurate in vivo therapeutic potential can be assessed, but financial costs increase and ethical constraints limit the number of tests that can be performed

Engineering Contradiction:
Improvein vivo efficacy assessment accuracyVSAvoidtesting system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the phage testing pipeline into distinct stages: initial in vitro screening for rapid filtering, followed by in vivo testing in infected model organisms for therapeutic efficacy assessment, and finally clinical trials. This segmentation allows the majority of phage candidates to be evaluated and filtered at the simpler, less costly in vitro stage, reducing the number of expensive and ethically constrained animal tests needed while maintaining reliable assessment of therapeutic potential.

Inventive Principle:
Principle #1Segmentation

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

Enables rapid, cost-effective, and ethically unconstrained large-scale testing of bacteriophage therapeutic efficacy in vivo, identifying effective phages that can adapt to specific bacterial strains and demonstrating therapeutic potential in multicellular organisms.

Implementation Method 1

Naturally occurring bacteriophages, bacterial viruses, are a group of potential new-generation antibacterial drugs. They infect specific cells of their bacterial hosts and are harmless to eukaryotic cells.

Methodology Applied
Scientific EffectBacteriophage infection and lysis:

Data Source

PatentEP2872156B1A method of evaluating the therapeutic efficacy of bacteriophages
Publication Date: 2017.08.09 SZKOA GOWNA GOSPODARSTWA WIEJSKIEGO W WARSZAWIE
  • EP2872156B1 patent drawingFigure 1
  • EP2872156B1 patent drawingFigure 1
  • EP2872156B1 patent drawingFigure 1

AI summary

The subject of the present invention is a novel use of a nematode in the evaluation of the therapeutic efficacy of bacteriophage preparations used in, or capable of being used in the treatment of infections caused by pathogenic bacteria in humans or animals.