Acetylation of polyethylenimine enhances gene delivery via weakened polymer/DNA interactions

Nathan P. Gabrielson, Daniel W. Pack

Research output: Contribution to journalArticlepeer-review


We previously reported that gene delivery efficiency of 25-kDa, branched polyethylenimine (PEI) increased upon acetylation of up to 43% of the primary amines with acetic anhydride. In the present work, we investigated the effects of further increasing the degree of acetylation and elucidated the source of the higher gene delivery efficiency. Despite reduced buffering capacity, gene delivery activity continued to increase (up to 58-fold in HEK293) with acetylation of up to 57% of primary amines but decreased at higher degrees of acetylation. Characterization of polymer-DNA interactions showed that acetylated polymers bind less strongly to DNA. Further, a fluorescence resonance energy transfer assay showed that increasing acetylation causes polyplexes to unpackage inside cells to a higher degree than polyplexes formed with unmodified PEI. Overall, the data suggest that the increased gene delivery activity may be attributable to an appropriate balance between polymer buffering capacity and strength of polymer/DNA interactions.

Original languageEnglish (US)
Pages (from-to)2427-2435
Number of pages9
Issue number8
StatePublished - Aug 2006

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry


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