Polyplexes composed
of polyethyleneimine (PEI) and DNA or siRNA have attracted great attention
for their use in gene therapy. Although many physicochemical characteristics
of these polyplexes remain unknown, PEI/DNA complexes have been repeatedly
shown to be more stable than their PEI/siRNA counterparts. Here, we
examine potential causes for this difference using atomistic molecular
dynamics simulations of complexation between linear PEI and DNA or
siRNA duplexes containing the same number of bases. The two types
of polyplexes are stabilized by similar interactions, as PEI amines
primarily interact with nucleic acid phosphate groups but also occasionally
interact with groove atoms of both nucleic acids. However, the number
of interactions in PEI/DNA complexes is greater than in comparable
PEI/siRNA complexes, with interactions between protonated PEI amines
and DNA being particularly enhanced. These results indicate that structural
differences between DNA and siRNA may play a role in the increased
stability of PEI/DNA complexes. In addition, we investigate the binding
of PEI chains to polyplexes that have a net positive charge. The binding
of PEI to these overcharged complexes involves interactions between
PEI and areas on the nucleic acid surface that have maintained a negative
electrostatic potential and is facilitated by the release of water
from the nucleic acid
