Pg Outer Membrane Vesicles for NRG1 Targeting Across Biological Barriers

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

The nucleic acid profiles of Porphyromonas gingivalis (Pg) outer membrane vesicles (OMVs) have not been characterized, and their potential to modulate specific mammalian gene expression, particularly Neuregulin-1 (NRG1), which is associated with brain development and various disorders, remains unexplored.

Innovation Solution

Isolate Pg OMVs containing transfer ribonucleic acid (tRNA) complementary to NRG1 messenger ribonucleic acid (mRNA) and administer them to modulate NRG1 expression, using Pg OMVs as a gene therapy vector to treat conditions like cancer and neurological disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If Pg OMVs are used to modulate NRG1 expression, then gene targeting precision is improved, but delivery efficiency to specific tissues may be insufficient

Engineering Contradiction:

Improvegene targeting precisionVSAvoiddelivery efficiency

Core Design Contradiction:

Manufacturing precisionVSProductivity

Solution Approach 1:

The patent uses Porphyromonas gingivalis outer membrane vesicles (Pg OMVs) as intermediary carriers to deliver tRNA molecules to mammalian cells. The Pg OMVs serve as a natural delivery vehicle that protects the tRNA cargo and facilitates its transport across biological barriers, thereby improving both delivery efficiency and targeting precision simultaneously

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates a composite system combining bacterial OMV structures with therapeutic tRNA molecules. The OMV provides a protective outer shell with specific surface properties, while the encapsulated tRNA delivers the genetic targeting function, achieving both efficient delivery and precise gene modulation

Inventive Principle:

Principle #40Composite materials

2Adaptability or versatility

If Pg OMVs cross biological barriers like BBB, then therapeutic coverage is improved, but immune response risk increases

Engineering Contradiction:

Improvetherapeutic coverageVSAvoidimmune response risk

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent leverages the natural properties of Pg OMVs, which are derived from a bacterium that naturally interacts with host tissues. The OMVs have evolved to cross biological barriers without triggering strong immune responses, and the invention repurposes this capability for therapeutic delivery while minimizing immunogenicity through careful selection of the bacterial source and OMV preparation methods

Inventive Principle:

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

3Manufacturing precision

If tRNA complementary to NRG1 mRNA is delivered, then NRG1 expression control is improved, but off-target effects may occur

Engineering Contradiction:

Improveexpression control precisionVSAvoidoff-target effects

Core Design Contradiction:

Manufacturing precisionVSObject-generated harmful factors

Solution Approach 1:

The patent employs tRNA molecules with specifically designed complementary sequences that match only the target NRG1 mRNA. This sequence specificity ensures that the tRNA binds exclusively to its intended target, providing precise local control of gene expression while avoiding off-target effects on other genes or cellular processes

Inventive Principle:

Principle #3Local quality

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

Pg OMVs effectively reduce NRG1 expression, cross biological barriers, and modulate gene expression to treat conditions such as cancer and neurological disorders, while minimizing immune responses and promoting neurodevelopment.

Implementation Method 1

OMVs encapsulate a range of bacterial components that include, proteins, nucleic acids, LPS, toxins, and secondary metabolites. OMVs are traffickable within a host and will attach to bacteria and host cells to deliver their cargo in a concentrated manner.

Methodology Applied

Scientific EffectOuter membrane vesicle delivery:

Data Source

PatentUS20250235557A1Method of gene targeting utilizing outer membrane vesicle

Publication Date: 2025.07.24 RES INST AT NATIONWIDE CHILDRENS HOSPITAL

AI summary

A method of gene targeting utilizing outer membrane vesicle is disclosed. As described herein outer membrane vesicles (OMVs) have the ability to modulate the expression of NRG1 intracellularly, which affects intracellular NRG1 mediated functions in addition to autocrine and paracrine signaling that support cell development, differentiation and growth. The OMVs are useful in modifying the expression of NRG1 and the expression of genes other than NRG1. The Pg OMVs also function as a gene therapy vector, as it is up taken by mammalian cells and crosses both the placental and blood brain barrier.