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Saponin and fluorine-modified polycation as a versatile gene delivery system
Akbar Hasanzadeh1, Amir Hossein Vahabi1, Seyyed Emad Hooshmand1
1Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
Nanotechnology
|July 26, 2022
Summary
Researchers developed a novel PEI-PBA-SAP-F gene carrier for efficient genetic material delivery. This advanced vector shows low cytotoxicity and high transfection rates in various cell types, offering a promising solution for biomedical applications.
Area of Science:
- Biomaterials Science
- Gene Therapy
- Nanotechnology
Background:
- Efficient and safe gene delivery vectors are crucial for genetic therapies.
- Existing carriers often face challenges with high cytotoxicity or low transfection efficiency.
- Novel polycations are needed to overcome these limitations in gene delivery.
Purpose of the Study:
- To develop a novel, highly efficient, and low-cytotoxicity gene delivery vector.
- To functionalize low molecular weight polyethylenimine (PEI) with saponin and a fluorinated side chain.
- To create an ATP-responsive cross-linked polycation (PEI-PBA-SAP-F) for enhanced gene delivery.
Main Methods:
- Functionalization of low molecular weight polyethylenimine (PEI1.8k) with saponin residues.
- Utilizing phenylboronic acid (PBA) as an ATP-responsive cross-linker.
- Incorporating a fluorinated side chain to create the PEI-PBA-SAP-F polycation.
Main Results:
- PEI-PBA-SAP-F demonstrated outstanding transfection efficiency for small plasmid DNA (∼3 kb) in multiple cell lines (HEK 293T, NIH3T3, A549, PC12, MCF7, HT-29).
- Robust transfection of large plasmid DNA (∼9 kb) was achieved in HEK 293T cells.
- Effective gene delivery was observed even in high-serum conditions and with low plasmid doses.
- Successful transfection of various CRISPR/Cas9 complexes was confirmed using GFP knock-out analysis.
Conclusions:
- The developed PEI-PBA-SAP-F polycation is a highly efficient gene carrier.
- This vector exhibits a favorable lipophilic/cationic balance suitable for biomedical applications.
- The study presents a promising advancement in non-viral gene delivery systems.
