Genetically Modified P. acnes for Topical Growth Factor Delivery

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Solution Overview

Problem

Current dermatological treatments lack effective, non-invasive methods for delivering growth factors and cytokines directly to the skin to address various skin disorders.

Innovation Solution

Genetically modified Propionibacterium acnes (P. acnes) type II, ribotype 6 strains are engineered to express and secrete mammalian growth factors or cytokines, such as TGF-β, VEGF, and IL-10, using inducible promoters and CRISPR arrays, and are formulated for topical or mucosal administration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If genetically modified P. acnes strains are used to deliver growth factors and cytokines, then delivery effectiveness and targeting are improved, but safety concerns and immune response risks increase

Engineering Contradiction:

Improvedelivery effectivenessVSAvoidsafety concerns

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent utilizes the natural pathogenic properties of P. acnes against human cells and its ability to penetrate the skin barrier as beneficial features. The bacterium's inherent capacity to deliver molecules into cells is harnessed for therapeutic purposes, converting what would normally be harmful pathogenic mechanisms into useful delivery vehicles for growth factors and cytokines

Inventive Principle:

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

Solution Approach 2:

P. acnes serves as a living intermediary carrier that bridges the gap between external application and intracellular delivery. The bacterium acts as a mediator that can transport therapeutic molecules through the skin barrier and into target cells, solving the problem of how to effectively deliver growth factors and cytokines directly to skin cells

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If conventional dermatological treatments are used, then safety is maintained, but delivery effectiveness and ability to address skin disorders is insufficient

Engineering Contradiction:

ImprovesafetyVSAvoiddelivery effectiveness

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The P. acnes bacterium utilizes its own natural biological functions and pathogenic mechanisms to deliver the therapeutic payload. The bacterium's inherent ability to penetrate barriers and interact with host cells is leveraged, requiring no external delivery system or complex apparatus

Inventive Principle:

Principle #25Self-service

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 genetically modified P. acnes strains effectively deliver growth factors and cytokines to the skin, promoting wound healing, tissue regeneration, and immunomodulation, thereby addressing various skin disorders in a safe and targeted manner.

Implementation Method 1

the nucleic acid includes a regulatory element that drives the expression of the mammalian growth factor or the mammalian cytokine in the P. acnes strain

Methodology Applied

Scientific EffectGene expression regulation:

Implementation Method 2

the P. acnes strain comprises an endogenous CRISPR array, and the nucleic acid and regulatory element are integrated into the genome of the P. acnes strain

Methodology Applied

Scientific EffectProtein secretion:

Implementation Method 3

the P. acnes strain comprises an endogenous CRISPR array

Methodology Applied

Scientific EffectCRISPR gene editing:

Data Source

PatentEP3158054B1Genetically modified bacteria and methods for genetic modification of bacteria

Publication Date: 2025.02.19 CROWN LABORATORIES INC

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AI summary

Microbes can be genetically modified to express biomolecules that are beneficial to mammals and/or to reduce, or eliminate, expression of harmful virulence factors. The growth and viability of such genetically modified microbes can optionally be controlled by inducible promoters that regulate the expression of proteins that are essential to their growth and survival. Compositions comprising such genetically modified microbes as well as methods of making and using the same are disclosed herein.