Beyond Branching: Multiknot Structured Polymer for Gene Delivery.

[dystrophic epidermolysis bullosa]

Polymer-based transfection vectors are increasingly becoming the preferred alternative to viral vectors thanks to their safety and ease of production , but low transfection potency has limited their application . Many polycationic vectors show high efficiency in vitro , but their excessive charge density makes them toxic for in vivo applications . Herein , we demonstrate the synthesis of new and unique disulfide-reducible polymeric gene nanocarriers that exhibit significantly enhanced transfection potency and low cytotoxicity , particularly in skin cells , surpassing the efficiency of the well-known transfection reagents polyethylenimine (PEI ) and Lipofectamine 2000 . The unique three -dimensional (3 D ) "multiknot " vectors were synthesized from in situ deactivation enhanced atom transfer radical (co )polymerization (DE -ATRP ) of multivinyl monomers (MVMs ). The high transfection levels and low toxicity of this multiknot structured polymer in vitro , combined with its ability to mediate collagen VII expression in 3 D skin equivalents made from cells of recessive dystrophic epidermolysis bullosa patients , demonstrates its use as a platform nanotechnology which should be investigated further for dermatological disease therapies . Our findings suggest that the marked improvements stem from the dense multiknot architecture and degradable property , which facilitate both the binding and releasing process of the plasmid DNA .