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Octaarginine-modified multifunctional envelope-type nanoparticles for gene delivery

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.

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Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research (B) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, by the MEXT Grant-in-Aid for Young Scientists (B) and Scientific Research on Priority Areas, and by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. We thank the Hitachi High-Technologies Corporation for generously performing the cryo TEM observation. We thank Drs H Yoshida, Sarah E Millar, Deborah Lang, Carol Trempus and Mitch Eddy for helpful discussions. We also thank Dr Miriam Sander for helpful advice in writing the English manuscript.

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Correspondence to M Yamada or H Harashima.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Khalil, I., Kogure, K., Futaki, S. et al. Octaarginine-modified multifunctional envelope-type nanoparticles for gene delivery. Gene Ther 14, 682–689 (2007). https://doi.org/10.1038/sj.gt.3302910

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