Cationic Liposome mRNA Delivery Complex

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Solution Overview

Problem

Current mRNA delivery methods face challenges such as inefficient translation due to premature degradation and limited intracellular access, leading to suboptimal immune responses and safety concerns, particularly with RNA-based vaccines, which are unstable and susceptible to nucleases, and require high doses for effectiveness.

Innovation Solution

A composition using liposomes based on cationic lipids to deliver modified nucleotides, such as pseudouridine, which forms a stable [liposome + mRNA complex] that reduces inflammatory responses and enhances intracellular expression efficiency, allowing for effective protein synthesis and immune response induction with lower doses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If RNA is used as a tool for gene administration, then the risk of unwanted integration into the genome is minimized or avoided, but RNA is a highly unstable molecular species that may be readily degraded by ubiquitous RNases

Engineering Contradiction:
Improverisk of unwanted integration into the genomeVSAvoidstability of RNA
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent uses anionic liposomes as an intermediary carrier to deliver RNA into cells. The liposomes protect RNA from degradation by RNases in the extracellular environment and facilitate cellular uptake, thereby resolving the contradiction between RNA's safety profile and its instability.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs modified nucleotides (such as pseudouridine, 5-methylcytidine, and 2'-O-methyluridine) to chemically modify the RNA structure. These modifications change the physical and chemical parameters of RNA, increasing its resistance to nuclease degradation while maintaining its ability to direct protein synthesis.

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If free RNA is administered, then it can access intracellular compartments where the translational machinery resides, but free RNA is susceptible to degradation by nucleases in blood

Engineering Contradiction:
Improveability to access intracellular compartmentsVSAvoidsusceptibility to degradation by nucleases
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

Anionic liposomes serve as a protective intermediary that carries RNA through the bloodstream and facilitates its entry into cells. The liposome-RNA complex protects the RNA from nucleases during circulation while enabling cellular delivery, thus resolving the contradiction between accessibility and stability.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a nested structure where RNA is encapsulated within or associated with anionic liposomes. This nested configuration protects the inner RNA molecule from external degradation while maintaining its functional integrity for intracellular delivery and translation.

Inventive Principle:
Principle #7Nested doll (Nesting)

3Productivity

If high doses of mRNA vaccines are administered to ensure effectiveness, then immune response is achieved, but safety concerns increase and affordability is reduced

Engineering Contradiction:
Improveeffectiveness of mRNA vaccineVSAvoidsafety concerns and affordability
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent uses modified nucleotides to enhance the stability and translation efficiency of mRNA. This parameter change in the molecular structure allows for reduced dosing while maintaining or improving vaccine effectiveness, thereby addressing safety and affordability concerns.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

Anionic liposomes act as an efficient delivery mediator that improves mRNA uptake and protection. This enhanced delivery system increases the effectiveness of lower doses, reducing the amount of mRNA needed per vaccine dose and improving both safety and cost-effectiveness.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 [liposome + mRNA complex] achieves high expression efficiency and low inflammatory responses, improving the stability and efficacy of mRNA vaccines for treating diseases like cancer and viral infections while reducing the required dose and potential safety concerns.

Implementation Method 1

a composition for delivering modified nucleic acid-containing mRNA, which includes liposomes based on a cationic lipid

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatic Induction

Data Source

PatentEP4356933A1Composition for delivering modified nucleic acid-containing mRNA
Publication Date: 2024.04.24 EYEGENE INC
  • EP4356933A1 patent drawingFigure 1
  • EP4356933A1 patent drawingFigure 2
  • EP4356933A1 patent drawing

AI summary

Disclosed is a composition for delivering mRNA containing a modified nucleotide including liposomes based on a cationic lipid. The composition for delivering mRNA containing a modified nucleotide has superior storage stability and high expression efficiency in vivo, thus increasing the stability and efficiency of mRNA vaccines for cancer treatment or mRNA vaccines for preventing viral infections and other mRNA vaccines or therapeutics.