mRNA Lipid Composition for High Encapsulation and Delivery
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Solution Overview
Problem
Existing methods for delivering nucleic acids, particularly mRNA, face challenges in achieving high encapsulation rates and dose-dependent protein expression, with limitations in gene size and safety concerns associated with viral vectors.
Innovation Solution
A lipid composition comprising specific compounds represented by Formula (1) or their salts, combined with neutral lipids and optionally sterols, nonionic hydrophilic polymers, and other components, to enhance nucleic acid encapsulation and delivery efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If a viral vector is used for gene delivery, then gene introduction efficiency is improved, but gene size is limited and immunogenicity and safety concerns arise
Solution Approach 1:
The patent modifies the chemical structure of lipid molecules by varying the hydrocarbon chain lengths (R1: 6-24 carbons, R2: 1-6 carbons) and functional groups to optimize lipid nanoparticle properties for mRNA delivery, enabling high-efficiency delivery without viral vector limitations
Solution Approach 2:
The patent combines multiple lipid components including the specific compound of Formula (1), neutral lipids, and optionally sterols to create composite lipid nanoparticles that achieve both high encapsulation efficiency and effective delivery of nucleic acids
2Adaptability or versatility
If conventional lipid compositions are used for nucleic acid delivery, then any gene can be introduced without size limitation, but nucleic acid encapsulation rate and delivery efficiency are insufficient
Solution Approach 1:
The patent optimizes the hydrocarbon chain lengths and functional groups of the lipid compound to enhance its ability to encapsulate and deliver nucleic acids effectively
Solution Approach 2:
The patent introduces specific functional groups (amino groups, carboxyl groups, hydroxyl groups) at specific positions of the lipid molecule to enhance local interactions with nucleic acids, improving encapsulation efficiency
3Adaptability or versatility
If mRNA is used for protein expression, then protein production can be achieved, but high encapsulation rate and dose-dependent production are difficult to realize
Solution Approach 1:
The patent optimizes the lipid compound parameters including hydrocarbon chain length (R1: 6-24 carbons, R2: 1-6 carbons) and functional groups to enhance mRNA encapsulation efficiency and enable dose-dependent protein expression
Solution Approach 2:
The patent formulates composite lipid nanoparticles combining the specific compound of Formula (1) with neutral lipids and optionally sterols to achieve both high encapsulation rates and effective mRNA delivery for dose-dependent protein production
Data Source
Figure 1
AI summary
An object of the present invention is to provide a compound or a salt thereof, which constitutes a lipid composition capable of realizing a high nucleic acid encapsulation rate and excellent nucleic acid delivery in a case where mRNA is used; and a lipid composition, a pharmaceutical composition, and a delivery carrier, which are capable of realizing a high nucleic acid encapsulation rate and excellent nucleic acid delivery in a case where mRNA is used. According to the present invention, a compound represented by Formula (1) or a salt thereof is provided. In the formula, R1 represents a hydrocarbon group having 1 to 24 carbon atoms, R2 represents a hydrocarbon group having 1 to 6 carbon atoms, R3 represents a hydrocarbon group having 6 to 24 carbon atoms and having a branched chain, R4 and R5 represent a hydrocarbon group having 1 to 6 carbon atoms, which may be substituted, R6 represents a hydrogen atom or a hydrocarbon group having 1 to 18 carbon atoms, L represents *-O-C(O)- or *-C(O)O-, a represents an integer of 1 to 12, and b, c, and d represent an integer of 1 to 4.