Nonviral gene therapy focuses intensely on ammonium-containing macromolecules and lipids to condense and deliver DNA as a therapeutic for genetic human diseases.  For the first time, DNA binding and gene transfection experiments compared phosphonium-containing macromolecules to their respective ammonium analogs.  Conventional free radical polymerization of quaternized 4-vinylbenzyl chloride monomers afforded phosphonium- and ammonium-containing homopolymers for gene transfection experiments of HeLa cells.    Aqueous size exclusion chromatography confirmed similar absolute molecular weights for all polyelectrolytes.  DNA gel shift assays and luciferase expression assays revealed phosphonium-containing polymers bound DNA at lower charge ratios and displayed improved luciferase expression relative to the ammonium analogs.  Our studies demonstrated changing the polymeric cation from ammonium to phosphonium enables an unexplored array of synthetic vectors for enhanced DNA binding, endosomal escape, and protein expression that may transform the field of nonviral gene delivery.

Phosphonium-containing polyelectrolytes for nonviral gene delivery

243rd National Meeting (2012)

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