Mutant Listeria Bacteria for Interferon-β Production Modulation

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Solution Overview

Problem

Interferon-β stability in solutions is limited by degradation mechanisms such as aggregation and deamidation, restricting its clinical utility in treating diseases like cancer and viral infections.

Innovation Solution

Mutant Listeria bacteria with mutations in transcription regulator genes or multidrug resistance transporter genes are used to modulate interferon-β production in macrophages, providing a stable and effective method for interferon-β modulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If interferon-β is administered in purified form, then therapeutic efficacy is improved, but stability is worsened due to aggregation and deamidation

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidinterferon-β stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent uses Listeria bacteria as an intermediary delivery system to produce and release interferon-β in vivo, avoiding the stability issues of purified interferon-β in solution. The bacterial host provides a stable environment for interferon-β production and controlled release, preventing aggregation and deamidation that occur in purified forms.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical/administrative system of purified protein administration with a biological production system using Listeria bacteria. This substitution allows interferon-β to be produced and delivered in a stable biological context rather than as an unstable purified protein solution.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Stability of the object's composition

If mutant Listeria bacteria are used to modulate interferon-β production, then stability is improved, but device complexity is worsened

Engineering Contradiction:
Improveinterferon-β stabilityVSAvoidbacterial system complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The Listeria bacteria serve multiple functions simultaneously: they act as the delivery vehicle, the production factory, and the controlled release mechanism for interferon-β. This multi-functionality reduces the need for separate stabilization systems, formulations, and administration protocols that would otherwise be required.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The mutant Listeria bacteria self-regulate interferon-β production through their genetic modifications, automatically producing and releasing the interferon in a controlled manner without requiring external stabilization systems or complex delivery infrastructure.

Inventive Principle:
Principle #25Self-service

Data Source

PatentUS9895433B2Interferon-β production modulating <i>listeria </i>strains and methods for using same
Publication Date: 2018.02.20 RGT UNIV OF CALIFORNIA
  • US9895433B2 patent drawing
  • US9895433B2 patent drawing
  • US9895433B2 patent drawing

AI summary

Mutant Listeria bacteria that modulate interferon-β production are provided. The subject bacteria are characterized by having a mutation in a gene chosen from a TetR gene, a LadR gene, a VirR gene, a MarR gene a MdrL gene, a MdrT gene and a MdrM gene. The subject bacteria find use in a variety of applications, where representative applications of interest include, but are not limited to: (a) use of the subject bacteria as adjuvants; (b) use of the subject bacteria as delivery vectors for introducing macromolecules into a cell; (c) use of the subject bacteria as vaccines for eliciting or boosting a cellular immune response; etc.