Polyion Complex mRNA Delivery via PEG-Block Copolymer Micelle

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Solution Overview

Problem

Current drug delivery systems face challenges in delivering mRNA into cells without inducing inflammation and ensuring uniform and sustained protein expression, particularly for treating diseases like fulminant hepatitis and dysosmia.

Innovation Solution

A polyion complex comprising a cationic polymer and mRNA, specifically a block copolymer of PEG and a polycation, forms a micelle structure that minimizes inflammatory reactions and enables efficient, uniform, and prolonged protein expression by encapsulating mRNA, allowing it to be delivered into cells without premature release.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If mRNA is delivered into cells using conventional drug delivery systems, then protein expression can be achieved, but inflammation is induced

Engineering Contradiction:
Improveprotein expressionVSAvoidinflammation
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses a polyion complex as an intermediary carrier between mRNA and cells. This complex, formed by cationic polymers and anionic polymers, mediates the delivery process by protecting mRNA from immune recognition while facilitating cellular uptake, thereby achieving protein expression without inducing inflammation

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the physical and chemical parameters of mRNA delivery by forming a polyion complex. This changes the charge, size, and stability characteristics of the delivery system, allowing mRNA to be delivered without triggering inflammatory responses while maintaining efficient protein expression

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If mRNA is delivered using polyion complexes, then inflammation is suppressed, but uniform and sustained protein expression must be ensured

Engineering Contradiction:
ImproveinflammationVSAvoidprotein expression uniformity and sustainability
Core Design Contradiction:
Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The patent employs a composite polyion complex structure combining cationic and anionic polymers. This composite material provides both protective encapsulation of mRNA and controlled release properties, ensuring uniform and sustained protein expression while suppressing inflammation

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent uses a nested structure where mRNA is encapsulated within the polyion complex core, which itself is covered by a PEG shell. This nested architecture protects mRNA, controls its release, and ensures sustained protein expression without inflammation

Inventive Principle:
Principle #7Nested doll (Nesting)

3Duration of action of moving object

If PEG covers the nanoparticle shell to increase biocompatibility, then blood residence time is enhanced, but mRNA delivery efficiency must be maintained

Engineering Contradiction:
Improveblood residence timeVSAvoidmRNA delivery efficiency
Core Design Contradiction:
Duration of action of moving objectVSReliability

Solution Approach 1:

The patent applies local quality by having different regions of the polyion complex serve different functions: the inner core provides mRNA encapsulation and delivery efficiency, while the outer PEG shell provides biocompatibility and extended blood residence time

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

The polyion complex effectively delivers mRNA encoding brain-derived neurotrophic factor or anti-apoptosis factors, achieving rapid and sustained protein expression in a wide range of cells, reducing inflammation and effectively treating diseases such as fulminant hepatitis and dysosmia.

Implementation Method 1

The present invention relates to a polyion complex of mRNA and a cationic polymer

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

PEG covers the shell of the nanoparticle, which is known to be convenient in terms of increasing biocompatibility and enhancing blood residence time

Methodology Applied
Scientific EffectSteric stabilization:

Data Source

PatentEP3106177B1Polyion complex comprising mRNA for therapy
Publication Date: 2022.07.27 NANOCARRIER CO LTD
  • EP3106177B1 patent drawingFigure 1A~1B
  • EP3106177B1 patent drawingFigure 2A~2B
  • EP3106177B1 patent drawingFigure 3A~3C

AI summary

[Problem to be Solved] The invention provides a composition and a pharmaceutical composition for delivering mRNA. [Solution] A polyion complex comprising a polycationic polymer and a messenger RNA (mRNA).