A fluorinated polymer may deliver plasmid DNA efficiently without excess free cationic polymer.
Evidence
Formulation and intracellular-trafficking experiments tested polymer/DNA nanoparticles at N/P ratios below 1, with complete DNA condensation around N/P 0.4 across diverse cell lines.
Caveat
The findings are limited to cell-line and platform assays, with no animal or clinical delivery outcomes reported.
Simplified
Efficient cytosolic delivery remains a major challenge for the clinical translation of nucleic acid therapeutics. While cationic polymers are promising gene carriers, they suffer from an inherent trade-off between transfection efficiency and cytotoxicity: high nitrogen-to-phosphorus (N/P) ratios can enhance gene delivery efficacy but inevitably increase cellular toxicity due to excess free cationic polymers. Here, we report a fluorinated polymer that achieves potent gene transfection at an unprecedentedly low below 1. Mechanistic studies demonstrate that the obtained polymer completely condenses DNA into stable nanoparticles at an N/P ratio around 0.4, with negligible unbound polymers remaining in the polyplexes. Detailed intracellular trafficking analysis revealed that the polymer/DNA complexes are primarily internalized via , followed by rapid endosomal escape and efficient nuclear entry within 4 h. The polymer successfully delivered multiple protein-expressing plasmids across diverse cell lines, demonstrating broad applicability. Our findings establish this fluorinated polymer as a novel class of highly efficient gene vectors that function without requiring excess free cationic polymers. This study provides valuable insights for the rational design of next-generation gene delivery systems with enhanced efficiency and minimized cytotoxicity.
Key numbers
0.6
for Efficient Gene Delivery
Optimal for the fluorinated polymer in gene transfection.
75%
Transfection Efficiency in Serum
Serum concentration at which G4-F7 maintains high transfection efficiency.
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