Lipid compound for gene delivery and lipid nanoparticle comprising same
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Solution Overview
Problem
Current lipid nanoparticles for nucleic acid delivery face challenges in efficiently reaching targeted cells and tissues due to limited ionizable lipid structures, which hinder therapeutic nucleic acid delivery efficacy.
Innovation Solution
Development of novel lipid compounds with asymmetric hydrophobic long chains and enhanced molecular flexibility, produced through a Ugi four-component reaction, enabling improved binding with target cell membranes and efficient intracellular delivery of nucleic acids.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If classical ionizable lipid structures are used in lipid nanoparticles, then the delivery system is well-established and manufacturable, but the ability to reach targeted cells and tissues is limited
Solution Approach 1:
The patent modifies the chemical structure of ionizable lipids by changing parameters such as chain length, saturation degree, and head group composition. Specifically, it introduces lipids with different hydrocarbon chain lengths (C16-C24), saturation levels (0-6 double bonds), and head group types (amines, amides, carbamates) to optimize delivery efficiency for different target cells and tissues while maintaining manufacturability
Solution Approach 2:
The patent creates composite lipid structures by combining hydrophobic hydrocarbon chains with hydrophilic head groups containing ionizable amine, amide, or carbamate functionalities. This composite approach allows the lipid nanoparticle to maintain structural integrity while providing adaptable surface properties for targeting different cell types
2Adaptability or versatility
If novel ionizable lipid structures are developed to improve target cell reach, then adaptability and delivery efficiency are enhanced, but structural complexity increases
Solution Approach 1:
The patent segments the ionizable lipid structure into distinct functional modules: a hydrophobic hydrocarbon chain segment (C16-C24) and a hydrophilic head group segment containing ionizable functionalities (amine, amide, carbamate). This modular segmentation allows independent optimization of each segment's properties while maintaining overall structural manageability and synthesis feasibility
Solution Approach 2:
The patent applies local quality by introducing specific functional groups at the head group region of the lipid molecule while keeping the hydrocarbon chain region relatively simple. The head group contains the ionizable amine, amide, or carbamate functionalities that provide adaptability for target cell recognition, while the hydrocarbon chain provides structural stability
Data Source
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AI summary
Disclosed herein are a lipid compound comprising an isonitrile or a carboxylic acid terminal group, and a preparation method therefor and the use thereof in the preparation of a lipid compound that can be used for gene delivery. Also disclosed herein are a lipid compound that can be used for gene delivery, and a preparation method therefor and the use thereof in gene delivery. Further disclosed herein are a liposome and a lipid nanoparticle comprising the lipid compound that can be used for gene delivery, and a gene delivery composition comprising the lipid compound, the liposome, or the lipid nanoparticle. The lipid compound, the liposome, the lipid nanoparticle and the gene delivery composition herein that can be used for gene delivery enable efficient compounding, protection, and intracellular and targeted delivery and release of biomolecules, such as nucleic acids in tissues and organs in vitro and in vivo.