Ionizable Lipid Nanoparticles for Nucleic Acid Cell Entry
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Solution Overview
Problem
Nucleic acid drugs face challenges in penetrating cell membranes due to their large molecular weight and negative charge, leading to degradation and loss of function, necessitating improved ionizable lipid molecules for effective delivery.
Innovation Solution
Development of an ionizable lipid molecule with a specific chemical formula (I) and its use in lipid nanoparticles to facilitate the delivery of nucleic acids into cells, including ASO, siRNA, miRNA, mRNA, and saRNA, enhancing cellular uptake and therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nucleic acid drugs are used directly, then they can regulate and control gene function, but they cannot penetrate cell membrane due to large molecular weight and negative charge
Solution Approach 1:
The patent uses ionizable lipid molecules as intermediary carriers to form lipid nanoparticles that encapsulate nucleic acid drugs. These lipid nanoparticles serve as mediators that enable the negatively charged nucleic acids to penetrate the cell membrane by forming complexes that can cross the membrane barrier, thereby resolving the contradiction between maintaining drug functionality and achieving cell entry.
Solution Approach 2:
The invention creates composite delivery systems consisting of ionizable lipids, phospholipids, cholesterol, and PEG molecules forming lipid nanoparticles. This composite material combines the properties of different components to achieve both protection of the nucleic acid drug and effective cell membrane penetration, solving the penetration problem while maintaining therapeutic efficacy.
2Reliability
If nucleic acid drugs are administered, then they can exert therapeutic effects, but they are highly susceptible to degradation by nucleases
Solution Approach 1:
The ionizable lipid molecules provide beforehand cushioning by forming protective lipid nanoparticle complexes around the nucleic acid drugs before administration. This protective layer shields the nucleic acids from nuclease degradation in the biological environment, allowing them to reach the target cells intact and maintain their therapeutic function.
3Productivity
If existing ionizable lipid molecules are used, then some delivery function is achieved, but improved delivery efficiency is still needed
Solution Approach 1:
The patent optimizes delivery efficiency by systematically adjusting parameters of the ionizable lipid molecules, including the hydrophobic chain length (m=3-6), the structure of R1-R5 groups, and the configuration of L1-L4 linkers. These parameter changes enable fine-tuning of the lipid nanoparticle properties to achieve enhanced cellular uptake and delivery efficiency without excessive structural complexity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The ionizable lipid molecule effectively delivers various nucleic acid drugs into cells, overcoming membrane penetration and degradation issues, thereby achieving therapeutic effects.
Implementation Method 1
The ionizable lipid molecule effectively delivers various forms of nucleic acid drugs such as ASO, siRNA, miRNA, mRNA, saRNA, sgRNA, etc., allowing different nucleic acid molecules to enter the cell
Data Source
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AI summary
An ionizable lipid molecule, a preparation method therefor and a use thereof. Specifically, provided are a compound represented by formula I, and a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug or solvate thereof. The definition of each group in the formula is as described in the description. Also provided is a lipid nanoparticle, containing the ionizable lipid compound represented by formula (I). Further provided are a composition and a related use. The compound of formula I can be used to prepare the lipid nanoparticle for delivering a nucleic acid therapeutic agent or an active agent in vivo and in vitro.