Histone H3 Tail Peptides
and Poly(ethylenimine) Have
Synergistic Effects for Gene Delivery
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Abstract
This goal of this work was to explore histone H3 tail
peptides
containing transcriptionally activating modifications for their potential
as gene delivery materials. We have found that these H3 tail peptides,
in combination with the cationic polymer poly(ethylenimine) (PEI),
can effectively bind and protect plasmid DNA. The H3/PEI hybrid polyplexes
were found to transfect a substantially larger number of CHO-K1 cells <i>in vitro</i> compared to both polyplexes that were formed with
only the H3 peptides and those that were formed with only PEI at the
same total charge ratio; however, transfection was similarly high
for polyplexes both with and without transcriptionally activating
modifications. Transfections with the endolysosomal inhibitors chloroquine
and bafilomycin A1 indicated that the H3/PEI hybrid polyplexes exhibited
slower uptake and a reduced dependence on endocytic pathways that
trafficked to the lysosome, indicating a potentially enhanced reliance
on caveolar uptake for efficient gene transfer. In addition, whereas
PEI polyplexes typically exhibit a cytotoxic effect, the H3/PEI hybrid
polyplexes did not compromise cell viability. In total, the current
studies provide new evidence for the potential role for histone-based
materials as effective gene transfer agents, and support for the importance
of subcellular trafficking for nonviral gene delivery