Ternary Complex of Plasmid DNA with Protamine and γ-Polyglutamic Acid for Biocompatible Gene Delivery System

Kosuke Kanda, Yukinobu Kodama, Tomoaki Kurosaki, Masanobu Imamura, Hiroo Nakagawa, Takahiro Muro, Norihide Higuchi, Tadahiro Nakamura, Takashi Kitahara, Masayuki Honda, Hitoshi Sasaki
2013 Biological and Pharmaceutical Bulletin  
The purpose of the present study was to investigate the usefulness of the ternary complex with protamine and γ-polyglutamic acid (γ-PGA), which are biodegradable materials for foods and medical products, as a safe gene delivery vector. We formed cationic binary complexes (plasmid DNA (pDNA)/protamine complexes) with high transfection efficiency. The binary complex showed slight toxicity probably related to its total cationic charge. Then, we formed ternary complexes (pDNA/protamine/γ-PGA
more » ... es) by addition of anionic polymer, γ-PGA, and they showed no cytotoxicity. The transfection efficiency of the pDNA/protamine/γ-PGA complexes was as high as that of the pDNA/protamine complexes, although their zeta potentials were different. Inhibition study of the gene expressions in B16-F10 cells suggested that pDNA/protamine complexes were taken up by caveolae-mediated endocytosis and macropinocytosis. On the other hand, pDNA/protamine/ γ-PGA complexes were taken up by clathrin-mediated endocytosis and macropinocytosis. Thus, we succeeded in developing the ternary complex as a safe gene delivery vector with biocompatible materials.
doi:10.1248/bpb.b13-00479 pmid:24189422 fatcat:tk6ms4vxbnalrechtkb3awsgbe