POS8-0472
Development of a Fluorinated Low-Molecular-Weight PEI for Delivery of Txndc5-Targeting CRISPR–Cas9 Plasmids toward Atherosclerosis Gene Therapy
Topic
S8. Frontiers of Functional Polymers in Biology and Medicine
When and Where
Sep 30, 2026
08:30 - 09:30
Room 301 (Grand Ballroom)
Session Chairs
Heesuk KIM
Jinhye BAE
Presenter(s)
WEI JEN HUANG (Department of Chemical Engineering, National Taiwan University)
Co-Author(s)
Abstract
Vessel atherosclerosis is a major cardiovascular disease associated with increased mortality and morbidity, and it is considered a key indicator for cardiovascular disease management. Gene therapy, such as plasmid DNA vaccination, can direct the expression of functional proteins and is considered a promising approach for treating atherosclerosis in the era of precision medicine. To effectively deliver Txndc5 (thioredoxin domain-containing 5)-targeting CRISPR-Cas9 plasmids and regulate protein expression to reduce atherosclerosis, we developed a non-viral delivery system for transporting therapeutic genes into target cells.
Heptafluorobutyric anhydride (HFBA) was used to modify low-molecular-weight polyethyleneimine (PEI1.8k), resulting in a novel fluorinated polycationic carrier named FPEI, which was used to condense with plasmids to form FPEI polyplexes. FPEI was synthesized via amidation between PEI and various amounts of HFBA, with a conjugation efficiency of approximately 50.2%.
Furthermore, fluorinated FPEI carriers exhibited excellent biocompatibility, maintaining high cell viability and significantly lower cytotoxicity than PEI25k. Importantly, fluorination substantially improved transfection efficiency compared with unmodified PEI1.8k, demonstrating the effectiveness of fluorine modification for gene delivery. TEM characterization revealed uniformly dispersed spherical polyplexes with favorable colloidal stability under physiological conditions. These findings indicate that FPEI polyplexes successfully combine high transfection efficiency with low cytotoxicity, providing a promising non-viral platform for CRISPR-Cas9–mediated treatment of atherosclerosis.
Heptafluorobutyric anhydride (HFBA) was used to modify low-molecular-weight polyethyleneimine (PEI1.8k), resulting in a novel fluorinated polycationic carrier named FPEI, which was used to condense with plasmids to form FPEI polyplexes. FPEI was synthesized via amidation between PEI and various amounts of HFBA, with a conjugation efficiency of approximately 50.2%.
Furthermore, fluorinated FPEI carriers exhibited excellent biocompatibility, maintaining high cell viability and significantly lower cytotoxicity than PEI25k. Importantly, fluorination substantially improved transfection efficiency compared with unmodified PEI1.8k, demonstrating the effectiveness of fluorine modification for gene delivery. TEM characterization revealed uniformly dispersed spherical polyplexes with favorable colloidal stability under physiological conditions. These findings indicate that FPEI polyplexes successfully combine high transfection efficiency with low cytotoxicity, providing a promising non-viral platform for CRISPR-Cas9–mediated treatment of atherosclerosis.
