Remarkable increase in nuclease resistance of plasmid DNA through supramolecular assembly with poly(ethylene glycol) poly(L-lysine) block copolymer

Supramolecular associates of DNA with Poly(ethylene glycol)-poly(L-lysine) block copolymers (PEG-PLL) were prepared in aqueous milieu, and the water solubility under charge-neutralized (stoichiometric) conditions was maintained. Associates thus prepared achieved remarkable resistance against nuclease attack, probably due to the formation of PEG palisade surrounding the ion-complexed core of the DNA with the PLL segment of the block copolymer. Further, to estimate the stability of the associate, the rate of interexchange reaction of DNA in the associate with poly(vinyl sulfonate) was evaluated from a method using a metachromasy of toluidine blue dye. Of interest, the nuclease resistance of DNA in PEG-PLL/DNA associate had an inverse correlation with the rate of interexchange reaction and, thus, progressively increased with an increase in the molecular weight of PLL segment in the block copolymer, indicating the substantial importance of block copolymer design for DNA stabilization.