Lipid Particle Compounds for High Nucleic Acid Encapsulation
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Solution Overview
Problem
Existing methods for delivering nucleic acids into cells, such as those using viral vectors, face limitations in gene size transfer and raise concerns over immunogenicity and safety, while lipid particles offer a solution but require compounds that enhance nucleic acid encapsulation and delivery efficiency.
Innovation Solution
Development of compounds represented by Formula (1) or their salts, which are incorporated into lipid particles to achieve high nucleic acid encapsulation rates and efficient delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If viral vectors are used for nucleic acid delivery, then gene transfer efficiency is improved, but gene size limitation and immunogenicity concerns arise
Solution Approach 1:
The patent modifies the chemical structure of lipid compounds by changing parameters such as the amino group substitution pattern (Formula 1 with specific R1-R12 groups), hydrocarbon chain length (R2 and R3 with 3-24 carbon atoms), and linking groups (L1 and L2 with specific oxygen-containing or carbonyl-containing linkages). These parameter changes in the lipid compound structure enable the formation of lipid particles with enhanced nucleic acid encapsulation capability, allowing transfer of larger gene sizes while maintaining delivery efficiency.
2Productivity
If viral vectors are used for nucleic acid delivery, then gene transfer efficiency is improved, but safety and immunogenicity concerns arise
Solution Approach 1:
The patent employs synthetic lipid compounds (Formula 1) that form non-viral lipid particles as disposable, non-integrating delivery vehicles. Unlike viral vectors that can integrate into host genome and cause long-term immunogenicity, these lipid particles are designed for single-use transient delivery, eliminating persistent safety concerns and immunogenicity while maintaining efficient nucleic acid transfer.
Solution Approach 2:
The patent creates composite lipid particles comprising synthetic lipid compounds (Formula 1) combined with nucleic acids. This composite structure integrates the benefits of synthetic chemistry (customizable structure, low immunogenicity) with the functionality of nucleic acid delivery, achieving safe and effective gene transfer without viral components.
3Adaptability or versatility
If conventional lipid particles are used, then gene size limitation is resolved, but nucleic acid encapsulation rate and delivery efficiency need improvement
Solution Approach 1:
The patent introduces specific functional groups at localized positions in the lipid compound structure (Formula 1 with amino groups at specific locations, R1-R12 substituents, and L1-L2 linking groups). These localized functional features create specific interaction sites that enhance nucleic acid binding and encapsulation efficiency, while the overall molecular framework accommodates various gene sizes.
Solution Approach 2:
The patent optimizes multiple parameters of the lipid compound including the hydrophobic hydrocarbon groups (R2 and R3 with 3-24 carbon atoms), the linking groups (L1 and L2 with specific oxygen-containing or carbonyl-containing structures), and the amino group substitutions (R1 with 6-24 carbon atoms). These parameter optimizations collectively enhance both the encapsulation rate and delivery efficiency while maintaining the ability to accommodate large gene sizes.
Data Source
AI summary
An object of the present invention is to provide a compound or a salt thereof constituting lipid particles that can achieve a high nucleic acid encapsulation rate and excellent delivery of nucleic acids, and to provide lipid particles that can achieve a high nucleic acid encapsulation rate and excellent delivery of nucleic acids. According to an aspect of the present invention, a compound represented by Formula (1) or a salt thereof is provided.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 equal to or greater than 1, and c+d is equal to or greater than 1.