Ionizable Lipid Composition for High Nucleic Acid Encapsulation

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Solution Overview

Problem

Existing methods for delivering nucleic acids into cells face limitations in gene size and safety concerns, particularly with viral vectors, while lipid compositions offer flexibility but require improved encapsulation and delivery efficiency.

Innovation Solution

A compound represented by Formula (1) or its salt, combined with a lipid composition, enhances nucleic acid encapsulation and delivery by forming a lipid composition that includes neutral lipids and optionally sterols, proteins, peptides, or low-molecular-weight compounds.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If a viral vector is used for gene delivery, then gene introduction efficiency is improved, but gene size is limited and safety concerns arise

Engineering Contradiction:

Improvegene introduction efficiencyVSAvoidgene size limitation

Core Design Contradiction:

ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent modifies the chemical structure of lipid molecules by changing parameters such as chain length, saturation degree, and head group composition to optimize lipid nanoparticle properties for nucleic acid delivery, enabling efficient delivery without viral vector limitations

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses composite lipid formulations combining multiple lipid types (ionizable lipids, helper lipids, cholesterol, PEG-lipids) to create lipid nanoparticles that achieve both high delivery efficiency and expanded cargo capacity for various nucleic acid sizes

Inventive Principle:

Principle #40Composite materials

2Productivity

If a viral vector is used for gene delivery, then gene introduction efficiency is improved, but safety concerns arise

Engineering Contradiction:

Improvegene introduction efficiencyVSAvoidimmunogenicity and safety

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent employs non-viral lipid nanoparticle systems that are transient and do not integrate into the genome, avoiding the immunogenicity and long-term safety concerns associated with viral vectors while maintaining sufficient delivery efficiency

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent optimizes lipid composition parameters including ionizable lipid pKa, chain saturation, and head group charge to enhance cellular uptake and endosomal escape while minimizing immunogenic responses

Inventive Principle:

Principle #35Parameter changes

3Adaptability or versatility

If a lipid composition is used for gene introduction, then gene size flexibility is improved, but encapsulation rate needs enhancement

Engineering Contradiction:

Improvegene size flexibilityVSAvoidnucleic acid encapsulation rate

Core Design Contradiction:

Adaptability or versatilityVSQuantity of substance

Solution Approach 1:

The patent systematically varies lipid composition parameters including the ratio of ionizable to helper lipids, cholesterol content, and PEG-lipid concentration to maximize nucleic acid encapsulation efficiency while maintaining delivery functionality

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs multi-component lipid formulations where each lipid type contributes specific functions: ionizable lipids for endosomal escape, helper lipids for stability, cholesterol for membrane interaction, and PEG-lipids for steric stabilization, collectively achieving high encapsulation rates

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS20250345459A1Compound or salt thereof, lipid composition, pharmaceutical composition, and delivery carrier

Publication Date: 2025.11.13 FUJIFILM CORP

AI summary

An object of the present invention is to provide a compound or a salt thereof constituting lipid composition that can achieve a high nucleic acid encapsulation rate and excellent delivery of nucleic acids, and to provide a lipid composition, a pharmaceutical composition, and a delivery carrier, using the compound or a salt thereof. According to the present invention, a compound represented by Formula (1) or a salt thereof is provided.In the formula, R1, R2, R3, and R4 each independently represent a hydrogen atom or a hydrocarbon group having 1 to 24 carbon atoms, which may be substituted, R5 and R6 each independently represent a hydrocarbon group having 1 to 18 carbon atoms, which may be substituted, R7, R8, and R9 each independently represent a hydrocarbon group having 2 to 8 carbon atoms, and R5 and R6, or R5 and R7, may be combined to form a 4- to 7-membered ring.