Formula-Based Lipid Particles for Nucleic Acid Encapsulation and Delivery
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Solution Overview
Problem
Existing nucleic acid delivery methods, such as those using viral vectors, face limitations in gene size transfer and immunogenicity concerns, while lipid particles offer a solution but require compounds that enhance nucleic acid encapsulation and delivery efficiency.
Innovation Solution
Development of lipid particles using a compound represented by Formula (1) or its salt, which includes specific hydrocarbon groups and linking structures to achieve high nucleic acid encapsulation 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 is limited and immunogenicity concerns arise
Solution Approach 1:
The patent modifies the chemical structure of lipid molecules by changing parameters such as chain length, saturation, and head group composition to create lipid particles that can accommodate larger genes while maintaining delivery efficiency
Solution Approach 2:
The patent uses composite lipid formulations combining multiple lipid types (ionizable lipids, helper lipids, cholesterol) to create particles that overcome the limitations of single-component systems, enabling both high efficiency and large cargo capacity
2Productivity
If viral vectors are used for nucleic acid delivery, then gene transfer efficiency is improved, but immunogenicity and safety concerns arise
Solution Approach 1:
The patent employs synthetic lipid particles as disposable, non-replicating delivery vehicles that lack the immunogenicity of viral systems while providing equivalent or superior transfection efficiency
Solution Approach 2:
The patent adjusts lipid composition parameters including pH-responsive ionizable groups and biocompatible head groups to reduce immunogenicity while maintaining cellular uptake efficiency
3Adaptability or versatility
If conventional lipid particles are used, then any gene size can be transferred, but nucleic acid encapsulation rate and delivery efficiency need improvement
Solution Approach 1:
The patent optimizes lipid parameters including chain length (C16-C24), saturation degree, and head group pKa to enhance electrostatic interactions with nucleic acids, thereby improving encapsulation efficiency while maintaining size flexibility
Solution Approach 2:
The patent combines ionizable lipids with helper lipids and cholesterol in specific ratios to create composite particles that achieve both high encapsulation efficiency and flexible cargo capacity
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.