Plasmid DNA mono-ion complex stabilized by hydrogen bond for in vivo diffusive gene delivery.
Our original concept of the mono-ion complex (MIC) between plasmid DNA (pDNA) and a monocationic biocompatible polymer has been stabilized by hydrogen bond formation. To form the hydrogen bond with pDNA, ω-amide-pentylimidazolium end-modified poly(ethylene glycol), that is, APe-Im-PEG, has been synthesized. Agarose gel retardation assay and circular dichroism measurement have revealed that the MIC between pDNA and APe-Im-PEG has been stabilized by the hydrogen bond between pDNA and the ω-amide group and that the stable MIC has surprisingly further migrated into gel, as compared with naked pDNA. The rise of melting temperature suggests that the specific hydrogen bond forms between an adenine-thymine base pair and the ω-amide group. The resulting pDNA MIC with APe-Im-PEG has enhanced gene expression by intramuscular administration in mice, as compared with a poly(ethylenimine) polyion complex (PIC). These results suggest that the pDNA MIC is diffusive in vivo administration site, as compared with pDNA PICs. Our methodology for MIC stabilization by a ω-amide group is expected to offer superior supramolecular systems to those by ubiquitous PICs for in vivo diffusive gene delivery.
†Department of Applied Chemistry, Tokyo Metropolitan University, 1-1 minami-Osawa, Hachioji, Tokyo 192-0397, Japan.
Shoichiro
S
Asayama
†Department of Applied Chemistry, Tokyo Metropolitan University, 1-1 minami-Osawa, Hachioji, Tokyo 192-0397, Japan.
Atsushi
A
Nohara
‡Department of Drug Delivery and Molecular Biopharmaceutics, Tokyo University of Pharmacy and Life Sciences, Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Yoichi
Y
Negishi
†Department of Applied Chemistry, Tokyo Metropolitan University, 1-1 minami-Osawa, Hachioji, Tokyo 192-0397, Japan.
Hiroyoshi
H
Kawakami
D000818:Animals; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D018014:Gene Transfer Techniques; D056945:Hep G2 Cells; D006801:Humans; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000737:chemistry; D051379:Mice; D008813:Mice, Inbred ICR; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry
D007093:Imidazoles; D011092:Polyethylene Glycols; D004247:DNA