Lipid Nanoparticle Composition for Nucleic Acid Delivery

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Solution Overview

Problem

Nucleic acid therapeutics face challenges such as low cell permeability and high susceptibility to degradation, particularly for RNA molecules, limiting their delivery and efficacy in therapeutic and prophylactic applications.

Innovation Solution

Development of lipid nanoparticles comprising specific lipid compounds, including cationic lipids, neutral lipids, and polymer conjugated lipids, to facilitate the delivery of nucleic acid molecules, such as antisense and messenger RNA, by forming complexes that enhance cellular uptake and stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Device complexity

If nucleic acid molecules are used directly for delivery, then the delivery process is simple, but cell permeability is low and susceptibility to degradation is high

Engineering Contradiction:
Improvedelivery system complexityVSAvoidcell permeability and stability
Core Design Contradiction:
Device complexityVSReliability

Solution Approach 1:

The patent uses composite lipid materials including ionizable lipids, neutral lipids, and PEGylated lipids to form lipid nanoparticles that encapsulate nucleic acids. This composite approach provides both protection against degradation and enhanced cell permeability while maintaining manageable formulation complexity

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The lipid nanoparticle forms a flexible lipid bilayer shell around the nucleic acid cargo. This thin film structure protects the encapsulated nucleic acid from enzymatic degradation while allowing cellular uptake through endosomal escape mechanisms

Inventive Principle:
Principle #30Flexible shells and thin films

2Reliability

If lipid nanoparticles are used to deliver nucleic acids, then cell permeability and stability are improved, but the formulation complexity increases

Engineering Contradiction:
Improvecell permeability and stabilityVSAvoidformulation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent optimizes specific parameters including the pKa of ionizable lipids (5.5-8.5), lipid to nucleic acid ratio (1:1 to 10:1), and nanoparticle size (50-200 nm). These parameter optimizations achieve reliable delivery while standardizing the formulation process to manage complexity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces auxiliary components such as cholesterol as a structural mediator and PEGylated lipids as surface modifiers that facilitate nanoparticle formation and stabilization. These intermediaries simplify the overall formulation by performing specialized functions that enable reliable delivery

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 lipid nanoparticles improve the delivery and stability of nucleic acid molecules, overcoming permeability and degradation issues, thereby enhancing their therapeutic and prophylactic potential, including in vaccination and gene therapies.

Implementation Method 1

lipid nanoparticles comprising specific lipid compounds, including cationic lipids, neutral lipids, and polymer conjugated lipids, to facilitate the delivery of nucleic acid molecules

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

forming complexes that enhance cellular uptake and stability

Methodology Applied
Scientific EffectPhysical encapsulation: Physical Containment

Data Source

PatentEP4077272B1Lipid nanoparticle composition
Publication Date: 2024.09.18 SUZHOU ABOGEN BIOSCIENCES CO LTD
  • EP4077272B1 patent drawingFigure 1
  • EP4077272B1 patent drawingFigure 2
  • EP4077272B1 patent drawing

AI summary

Provided herein are lipids that can be used in combination with other lipid components, such as neutral lipids, cholesterol and polymer conjugated lipids, to form lipid nanoparticles for delivery of therapeutic agents (e.g., nucleic acid molecules) for therapeutic or prophylactic purposes, including vaccination.