Disulfide Cationic Polymers for Low-Toxicity Gene Delivery
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Solution Overview
Problem
Current cationic polymers used for gene delivery are toxic due to poor biocompatibility and nondegradability, posing challenges for safe and effective gene therapy applications.
Innovation Solution
Development of cationic poly(hydroxylalkyleneimine disulfide) polymers through polymerization of 1,ω-dibromoalkyl and ω,ω-diaminoalkyl disulfide monomers, optionally with 1,ω-diaminoalkyl monomers, to enhance transfection properties while reducing toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cationic polymers (PEI, poly-L-lysine) are used for gene delivery, then transfection efficiency is improved, but toxicity increases due to poor biocompatibility and nondegradability
Solution Approach 1:
The patent modifies the chemical structure of cationic polymers by incorporating hydrolyzable bonds (esters, amides, carbamates, urethanes) instead of purely stable bonds. This changes the degradation parameter of the polymer, allowing it to break down into non-toxic products (amino acids, alcohols, CO2) while maintaining transfection efficiency. The controlled hydrolysis provides a balance between stability for DNA binding and degradability for reduced toxicity.
Solution Approach 2:
The patent creates composite polymer structures combining cationic functional groups (for DNA binding and transfection) with hydrolyzable linkages (for controlled degradation). The composite nature includes both stable and labile bonds, allowing the material to perform dual functions: efficient gene delivery and biocompatible degradation. Examples include poly(amino ester)s, poly(amido amine)s, and poly(β-amino ester)s.
2Stability of the object's composition
If cationic polymers with high stability are used, then DNA binding and delivery capability is improved, but biodegradability deteriorates
Solution Approach 1:
The patent segments the polymer backbone into modular units connected by hydrolyzable bonds. Instead of a fully stable continuous chain, the polymer is divided into repeat units (amino acid residues, alcohol groups) linked by ester, amide, carbamate, or urethane bonds that can be cleaved by hydrolysis. This segmentation allows controlled breakdown into smaller non-toxic fragments while maintaining overall structural integrity for DNA complexation.
Solution Approach 2:
The patent introduces dynamic characteristics to the polymer structure by incorporating bonds with controlled hydrolysis rates. The polymer transitions from a static stable structure to a dynamic system that gradually degrades over time through hydrolytic cleavage. This dynamic behavior allows the polymer to maintain stability during DNA delivery then progressively degrade, adapting its stability over time to reduce accumulation and toxicity.
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 new polymers provide efficient nucleic acid delivery with reduced toxicity, ensuring safer and more effective gene therapy outcomes.
Implementation Method 1
The polymers of formula (I) and their salts can be degraded by cleavage of the disulfide bonds present in said polymers with reducing agents such as, but not limited to, dithiothreitol (DTT), beta-mercaptoethanol (BME), glutathione (GSH), cysteine (CYS) and cysteamine (CES).
Data Source
AI summary
Disclosed herein are poly(hydroxylalkyleneimine disulfide)polymers, which have both desirable transfection properties and reduced toxicity.