Nucleic Acid Complex Using Cyclic Dextrin for Safe Delivery
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Solution Overview
Problem
Current non-viral vectors for nucleic acid delivery, such as siRNA, face challenges with low stability, high toxicity, and inefficient intracellular persistence, limiting their therapeutic effectiveness in gene therapies.
Innovation Solution
A nucleic acid complex is formed using highly branched cyclic dextrin with a degree of polymerization of 50 to 5000, combined with a nucleic acid delivery carrier comprising diacylphosphatidylcholine, cholesterol, and an aliphatic primary amine, to enhance stability and intracellular delivery efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If non-viral vectors are used for nucleic acid delivery, then safety is improved, but intracellular delivery efficiency deteriorates
Solution Approach 1:
The patent uses a composite delivery system combining highly branched cyclic dextrin (polysaccharide) with cationic lipids to form a hybrid non-viral vector. This composite structure leverages the biocompatibility of dextrin while incorporating the membrane-disrupting capability of cationic lipids, achieving both safety and enhanced intracellular delivery efficiency without viral components
Solution Approach 2:
The patent modifies the chemical structure parameters of the dextrin by introducing specific functional groups (carboxyl, amino, or hydroxyl groups) at controlled ratios. This parameter optimization allows tuning of the vector's charge density and interaction properties with nucleic acids and cell membranes, balancing safety and delivery efficiency
2Productivity
If cationic polymers are used to form nucleic acid complexes, then intracellular delivery ability is improved, but cytotoxicity increases
Solution Approach 1:
The patent carefully controls the ratio of ionizable amino groups to carboxyl groups (N/C ratio) within specific ranges (0.5-2.0) to optimize the balance between positive charge for cellular uptake and reduced toxicity. This parameter optimization prevents excessive cytotoxicity while maintaining adequate intracellular delivery capability
Solution Approach 2:
The patent combines cationic dextrin derivatives with anionic lipids or neutral lipids to create a composite vector system. This composite approach distributes the toxicological burden and creates a more biocompatible surface profile while retaining the essential cationic interactions needed for intracellular delivery
3Productivity
If nucleic acids are delivered into cells rapidly, then delivery efficiency is improved, but persistent maintenance deteriorates
Solution Approach 1:
The patent creates a dynamic delivery system where the vector structure evolves within the cell. The endosome-lysosome escape mechanism allows the vector to transition from a stable extracellular complex to an active intracellular state, releasing nucleic acids at the optimal time and location for persistent expression while maintaining initial delivery efficiency
4Duration of action of stationary object
If highly branched cyclic dextrin with specific structure is used, then intracellular persistence is improved, but complex formation difficulty increases
Solution Approach 1:
The patent optimizes the degree of branching and molecular weight of cyclic dextrin within specific ranges to achieve optimal intracellular persistence while maintaining reasonable complex formation characteristics. The controlled introduction of functional groups at specific ratios further tunes the self-assembly properties to facilitate complex formation
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 nucleic acid complex achieves persistent and safe intracellular delivery of nucleic acids, improving therapeutic efficacy and reducing toxicity, making it suitable for gene therapy applications.
Implementation Method 1
a nucleic acid complex comprising a nucleic acid and a highly branched cyclic dextrin
Implementation Method 2
a nucleic acid delivery carrier comprising (A) a diacylphosphatidylcholine, (B) cholesterol and/or a derivative thereof, and (C) an aliphatic primary amine
Data Source
Figure 1~2
Figure 3
AI summary
The present invention provides a nucleic acid complex with low toxicity and high safety that can persistently maintain a nucleic acid, such as siRNA or the like, in a cell; and a nucleic acid delivery composition that can efficiently deliver the nucleic acid complex into a cell. A nucleic acid complex with low toxicity and high safety that can persistently maintain a nucleic acid in a cell can be obtained by forming a complex using a nucleic acid to be introduced into a cell, and a highly branched cyclic dextrin. Moreover, when a carrier comprising (A) a diacylphosphatidylcholine, (B) cholesterol and/or a derivative thereof, and (C) an aliphatic primary amine is used as a nucleic acid delivery carrier to introduce the nucleic acid complex into a cell, the safety, the efficiency of intracellular delivery, and the persistence of the nucleic acid in the cell can be further improved.