Viral Vector Gene Delivery for Antimicrobial Resistance

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Solution Overview

Problem

Current antimicrobial treatments often result in adverse side effects and the development of antimicrobial resistance in microbes, posing a significant health threat due to the toxicity of medications and the ability of microbes to develop resistance mechanisms.

Innovation Solution

The use of recombinant viral vectors to deliver antimicrobial resistance genes to eukaryotic cells, which express efflux pumps or enzymes that modify antimicrobial agents, allowing these agents to be pumped out of cells or rendered inactive, thereby reducing toxicity to the patient and maintaining efficacy against pathogens.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antimicrobial medications are administered to kill microbes, then the effectiveness against pathogens is improved, but the toxicity to the patient increases causing adverse side effects

Engineering Contradiction:

Improveeffectiveness against pathogensVSAvoidtoxicity to patient

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention divides the treatment approach into two separate components: (1) a viral vector that delivers antimicrobial resistance genes to eukaryotic cells to confer protection, and (2) the antimicrobial medication that kills microbes. This segmentation allows the toxic effects to be localized to microbial cells only, while eukaryotic cells are protected by the expressed resistance genes, thereby maintaining effectiveness while reducing overall toxicity to the patient.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The viral vector acts as an intermediary that delivers the antimicrobial resistance genes to eukaryotic cells before antimicrobial treatment. This intermediary mechanism prepares the host cells in advance to withstand the toxic effects of antimicrobial medications, allowing the drugs to kill microbes without harming the patient's eukaryotic cells.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If antimicrobial medications are used to treat infections, then the ability to kill microbes is improved, but the development of antimicrobial resistance in microbes worsens

Engineering Contradiction:

Improveability to kill microbesVSAvoidresistance development in microbes

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

Instead of trying to prevent resistance development through conventional means, the invention inverts the approach by making the host eukaryotic cells resistant to the antimicrobial medication through viral vector-mediated gene delivery. This reverses the traditional problem-solution dynamic: rather than microbes developing resistance to the drug, the host cells now possess resistance, allowing the use of potent antimicrobials that microbes cannot resist.

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The invention converts the potential harm of antimicrobial resistance into a benefit by using viral vectors to deliver resistance genes to host cells. The mechanism that normally allows microbes to survive (resistance gene expression) is instead applied to eukaryotic cells, turning the problem of resistance into a protective advantage for the host while maintaining the ability to kill microbial pathogens.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Productivity

If high doses of antimicrobial medications are administered to ensure pathogen elimination, then the effectiveness against pathogens is improved, but the adverse side effects increase in incidence and severity

Engineering Contradiction:

Improvepathogen elimination efficiencyVSAvoidadverse side effects

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The invention segments the protective function from the therapeutic function: eukaryotic cells receive resistance genes through viral vectors (protective function), while the antimicrobial medication focuses solely on pathogen elimination (therapeutic function). This segmentation enables high-dose antimicrobial administration for maximum pathogen killing without the usual concern for host toxicity, as the resistance genes protect eukaryotic cells from adverse effects.

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

This approach reduces the incidence and severity of side effects from antimicrobial medications while enhancing their effectiveness against pathogens by increasing their concentration at the infection site and preventing resistance development in eukaryotic cells.

Implementation Method 1

recombinant viral vectors to deliver antimicrobial resistance genes to eukaryotic cells

Methodology Applied

Scientific EffectGene delivery:

Implementation Method 2

express efflux pumps or enzymes that modify antimicrobial agents, allowing these agents to be pumped out of cells

Methodology Applied

Scientific EffectEfflux pump: Pump

Implementation Method 3

express efflux pumps or enzymes that modify antimicrobial agents, allowing these agents to be pumped out of cells or rendered inactive

Methodology Applied

Scientific EffectEnzyme modification: Enzyme

Data Source

PatentUS11185555B2Method to kill pathogenic microbes in a patient

Publication Date: 2021.11.30 HARRISON NOAH JAMES

AI summary

An improved method to kill pathogenic microbes in a patient is disclosed and claimed. The improved method includes transducing eukaryotic cells of the patient with a first viral vector that will not transfect the pathogenic microbes. The first viral vector is replication defective and encodes in its recombinant genome a first antimicrobial resistance gene and a promoter. An antimicrobial medication is administered to the patient.