ArticleBiomacromolecules2026
Gene Delivery Mediated by Backbone-Degradable RAFT Copolymers.
Article in Biomacromolecules, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Cationic polymers present an attractive platform for gene delivery. However, these highly charged macromolecules can also lead to cytotoxicity. Therefore, there is a strong unmet need to develop efficacious polymeric gene delivery vehicles with high biocompatibility. Here, we leverage recent advances in polymer chemistry to develop backbone-degradable cationic copolymers and evaluate their potential as gene delivery vehicles. Specifically, polycations were prepared via copolymerization with macrocyclic allylic sulfides, which can participate in PET-RAFT polymerization via radical ring-opening cascade copolymerization to install degradable backbone segments. A polymer library with varying degradabilities was prepared and evaluated using a model GFP plasmid to transfect U-2 OS cells. Incorporation of degradable groups into the copolymer backbone improved transfection efficiency 10-fold at low amine/phosphate (N/P) ratios without increasing cytotoxicity, thereby enhancing their value as gene delivery carriers. We hypothesize that degradability may enhance the complex's disassembly kinetics in the cytosol, enabling more efficient payload release.
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