Sucrose Ester Cationic Lipid Gene Vector

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Solution Overview

Problem

Current gene therapy methods face limitations due to the low transfection efficiency and high toxicity of existing non-viral gene vectors, particularly cationic lipids, which hinder their clinical application, while viral vectors have drawbacks such as high immunogenicity and carcinogenicity.

Innovation Solution

Development of sucrose ester-based cationic lipid compounds and complexes, synthesized through specific esterification reactions, which form biocompatible and degradable gene vectors with improved transfection efficiency and reduced cytotoxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If viral vectors are used for gene delivery, then transfection efficiency is improved, but immunogenicity and carcinogenicity increase

Engineering Contradiction:
Improvetransfection efficiencyVSAvoidimmunogenicity and carcinogenicity
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces persistent viral vectors with biodegradable sucrose ester-based cationic lipids that are metabolized by the body, eliminating long-term safety concerns while maintaining transfection efficiency. The sucrose ester structure is designed to be broken down into natural metabolites.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The invention creates composite cationic lipid structures combining sucrose ester backbone with hydrophobic tail groups, forming amphiphilic molecules that can self-assemble into liposomes for gene delivery. This composite structure provides both efficiency and safety.

Inventive Principle:
Principle #40Composite materials

2Object-affected harmful factors

If non-viral gene vectors are used, then immunogenicity and toxicity are reduced, but transfection efficiency decreases

Engineering Contradiction:
Improvetoxicity and immunogenicityVSAvoidtransfection efficiency
Core Design Contradiction:
Object-affected harmful factorsVSProductivity

Solution Approach 1:

The patent optimizes the cationic charge density and hydrophobicity parameters of the sucrose ester lipids to achieve optimal transfection efficiency. The cationic nitrogen groups provide electrostatic interaction with DNA while the hydrophobic tails enable membrane fusion, balancing efficiency and safety.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The sucrose ester cationic lipids act as intermediaries that facilitate DNA delivery without direct viral involvement. They form lipoplexes with DNA and mediate cellular uptake through endocytosis, providing a safe intermediate mechanism between non-viral vectors and cellular delivery.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If existing cationic lipids are used for gene delivery, then gene transport capability is achieved, but cytotoxicity increases

Engineering Contradiction:
Improvegene transport capabilityVSAvoidcytotoxicity
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The sucrose ester-based cationic lipids are designed as biodegradable, short-lived delivery vehicles that are metabolized into natural sucrose and fatty acid components, eliminating persistent cytotoxicity while maintaining gene transport capability during the delivery window.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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 sucrose ester-based cationic lipid vectors demonstrate superior transfection efficiency and lower cytotoxicity compared to existing reagents like Lipofectamine 2000 and DOTAP, offering a promising solution for safe and effective gene delivery.

Implementation Method 1

Sucrose ester prepared by using sucrose as a starting material can form a vesicular or double lamellar structure in the aqueous phase

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 2

Cationic liposomes which are positively charged at a physiological pH, can be self-assembled with negatively charged phosphate groups in a nucleic acid molecule to form liposome/gene complexes by means of an electrostatic interaction

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 3

the complexes can be adsorbed on the cell surface by the electrostatic interaction, and thereby introduce the exogenous genes into cells through cell endocytosis

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Data Source

PatentUS10279050B2Sucrose ester based cationic gene vector and preparation method thereof
Publication Date: 2019.05.07 DALIAN NATIONALITIES UNIVERSITY
  • US10279050B2 patent drawing
  • US10279050B2 patent drawing
  • US10279050B2 patent drawing

AI summary

The invention provides a class of sucrose ester based cationic lipids and preparation method thereof. The vector prepared using the cationic lipid can be used to deliver nucleic acid. The sucrose ester based cationic lipid is prepared by using a chemical synthesis method in the invention, wherein the synthesis method is simple, and has a relatively high product yield. A composition, including suspension, emulsion, micelle and liposome and the like, can be prepared by mixing the sucrose ester based cationic lipid compound of the invention with a co-lipid. Sucrose ester based cationic lipid complex can be prepared by using the said composition and nucleic acid, which has advantages such as simple preparation, low toxicity and high transfection efficiency, and is a novel and highly efficient gene vector.