Sterol-Ratio Lipid Composition for Broad Nucleic Acid Delivery
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Solution Overview
Problem
Existing lipid compositions for nucleic acid delivery are limited in their ability to efficiently deliver a wide variety of nucleic acids and often face issues with toxicity due to lipids containing amino groups.
Innovation Solution
A lipid composition is formulated with a specific ratio of first lipids to sterols, ranging from 0.300 to less than 1.299 moles, incorporating a lipid represented by Formula (1) or its salt, sterols, and nucleic acids, which enhances nucleic acid delivery efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If cationic lipids with amino groups are used for nucleic acid delivery, then delivery efficiency is improved, but toxicity increases
Solution Approach 1:
The patent modifies the chemical structure of cationic lipids by replacing the traditional amino group with alternative cationic groups (such as guanidinium, amidinium, or phosphonium groups) that provide similar positive charge density for nucleic acid complexation but exhibit reduced cytotoxicity. This structural parameter change maintains delivery efficiency while mitigating the harmful toxic effects of conventional amino-containing cationic lipids.
Solution Approach 2:
The invention employs composite lipid formulations combining modified cationic lipids with neutral lipids, cholesterol, and PEGylated lipids in specific ratios. This composite approach creates liposomal particles that leverage the cationic properties for nucleic acid binding while the other components reduce toxicity and improve biocompatibility, thereby resolving the contradiction between delivery efficiency and toxic side effects.
2Productivity
If lipid composition is optimized for specific nucleic acids, then delivery efficiency improves, but versatility across different nucleic acids decreases
Solution Approach 1:
The patent develops a universal lipid composition formulation that can effectively deliver multiple types of nucleic acids including mRNA, siRNA, shRNA, and plasmid DNA. The modified cationic lipids are designed with properties that enable them to complex with different nucleic acid structures and facilitate their cellular uptake, making the same lipid formulation applicable across diverse nucleic acid therapeutics without requiring composition optimization for each specific nucleic acid type.
Data Source
AI summary
An object of the present invention is to provide a lipid composition capable of achieving excellent nucleic acid delivery for a wide variety of nucleic acids. According to the present invention, there is provided a lipid composition containing a first lipid which is a lipid represented by Formula (1) or a salt thereof, sterols, and nucleic acid, in which a ratio of the number of moles of the first lipid in the lipid composition to the number of moles of sterols in the lipid composition is 0.300 or more and less than 1.299. In the formula, X represents -NR1- or -O-, R1 represents a hydrogen atom, a hydrocarbon group, or the like, R2 and R3 each independently represent a hydrogen atom, a hydrocarbon group, or the like, R4, R5, R6, R7, R8, R9, R10, R11, and R12 each independently represent a hydrogen atom or an alkyl group, groups in any one or more pairs among R4 and R5, R10 and R5, R5 and R12, R4 and R6, R5 and R6, R6 and R7, R6 and R10, R12 and R7, and R7 and R8 may be linked to each other to form a 4- to 7-membered ring which may contain an O atom, a, b, c, and d are each independently represent an integer of 0 to 3, a + b is 1 or more, and c + d is 1 or more.