Nucleic Acid-Lipid Nanoparticle Formulation for Stable Vaccine Delivery

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Solution Overview

Problem

Current nucleic acid-based vaccines, such as mRNA vaccines for COVID-19, face challenges in stability and the need for ultra-cold storage, which limits their distribution to areas without cold chain facilities. Additionally, effective delivery of DNA vaccines requires viral vectors or electroporation.

Innovation Solution

A nucleic acid-lipid nanoparticle (NA-LNP) composition is developed, comprising a nucleic acid molecule and a lipid mixture with specific ratios of ionizable amino lipid, phospholipid, cholesterol, and PEGylated lipid. This formulation enhances stability and delivery efficacy without the need for ultra-cold storage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If mRNA vaccines are used, then rapid production and scalability are achieved, but ultra-cold storage is required which limits distribution

Engineering Contradiction:
Improveproduction scalabilityVSAvoiddistribution feasibility
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent changes the storage temperature parameter from ultra-cold (mRNA requirement) to refrigerated storage conditions. The LNP formulation with specific lipid composition (ionizable cationic lipid, phospholipid, cholesterol, PEGylated lipid) enables the vaccine to remain stable and effective at higher temperatures, removing the need for ultra-cold chain while maintaining production scalability advantages of mRNA platforms

Inventive Principle:
Principle #35Parameter changes

2Stability of the object's composition

If DNA vaccines are used, then high stability and no ultra-cold storage are achieved, but effective delivery requires viral vector or electroporation

Engineering Contradiction:
Improvemolecule stabilityVSAvoiddelivery system complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent introduces LNP as an intermediary delivery system that bridges DNA stability advantages with simple administration. The lipid nanoparticle acts as a carrier that protects DNA from degradation and facilitates its delivery into cells through membrane fusion, eliminating the need for complex viral vectors or electroporation equipment while maintaining DNA's inherent stability

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces mechanical delivery methods (electroporation using electrical fields) and biological delivery methods (viral vectors) with a chemical/biophysical approach using lipid membrane fusion. The ionizable cationic lipid in the LNP formulation facilitates DNA entry through pH-dependent membrane fusion, a simpler process that requires no external energy input or complex machinery

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 NA-LNP formulation achieves effective delivery and induction of immune responses against coronavirus, including SARS-CoV-2, with improved stability and scalability, making it suitable for broader distribution and use as a vaccine platform.

Implementation Method 1

an ionizable amino lipid present in an amount of 20 mol % to 60 mol %

Methodology Applied
Scientific EffectIonization: Ionisation

Implementation Method 2

Both cholesterol and phospholipids are building block components embedded in the lipid bilayer of the cell membrane

Methodology Applied
Scientific EffectLipid bilayer membrane fusion:

Implementation Method 3

PEGylated lipidoids act as surfactants that stand out of the surface of LNP to reduce surface free energy between the lipophilic core and aqueous phase

Methodology Applied
Scientific EffectSurfactant action: Surfactant

Implementation Method 4

The formation of nucleic acid-LNP is a self-assembling process between two miscible fluids, a buffer solution of a nucleic acid molecule and a water-miscible solution (ethanol) comprising the lipids mixture

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Data Source

PatentUS20250127882A1Nucleic acid-lipid nanoparticle and method using the same
Publication Date: 2025.04.24 NATIONAL HEALTH RESEARCH INSTITUTE
  • US20250127882A1 patent drawing
  • US20250127882A1 patent drawing
  • US20250127882A1 patent drawing

AI summary

A nucleic acid-lipid nanoparticle is provided, which comprises: a nucleic acid molecule and a lipid mixture. The lipid mixture comprises: an ionizable amino lipid present in an amount of 20 mol % to 60 mol %; a phospholipid present in an amount of 5 mol % to 20 mol %; cholesterol present in an amount of 25 mol % to 60 mol %; and a PEGylated lipid present in an amount of 0.2 mol % to 6 mol %. In addition, methods using the aforesaid nucleic acid-lipid nanoparticle are also provided.