1. ¹Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, Hokkaido, Japan
2. ²The Core Research for Evolutional Science and Technology (CREST), Shibuya-ku, Tokyo, Japan
3. ³Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency (JST), Shibuya, Shibuya-ku, Tokyo, Japan
4. ⁴Institute for Chemical Research, Kyoto University, Uji, Kyoto, Japan
5. ⁵Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan
6. ⁶Yamada Research Unit, RIKEN Brain Science Institute, Saitama, Japan
7. ⁷National Institute of Environmental Health, Research Triangle Park, NC, USA
8. ⁸Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan

Correspondence: Professor H Harashima, Laboratory for Molecular Design of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Sapporo City, Hokkaido 060-0812, Japan. E-mail: harasima@pharm.hokudai.ac.jp; M Yamada, Yamada Research Unit, RIKEN Brain Science Institute, Saitama 351-0198, Japan. E-mail: masahisa@brain.riken.jp

⁹These authors contributed equally to this work.

Received 17 July 2006; Revised 3 December 2006; Accepted 3 December 2006; Published online 1 February 2007.

Abstract

This study describes a multifunctional envelope-type nano device (MEND) that mimics an envelope-type virus based on a novel packaging strategy. MEND particles contain a DNA core packaged into a lipid envelope modified with an octaarginine peptide. The peptide mediates internalization via macropinocytosis, which avoids lysosomal degradation. MEND-mediated transfection of a luciferase expression plasmid achieved comparable efficiency to adenovirus-mediated transfection, with lower associated cytotoxicity. Furthermore, topical application of MEND particles containing constitutively active bone morphogenetic protein (BMP) type IA receptor (caBmpr1a) gene had a significant impact on hair growth in vivo. These data demonstrate that MEND is a promising non-viral gene delivery system that may provide superior results to existing non-viral gene delivery technologies.