Acidic pH-Responsive siRNA Conjugate for Reversible Carrier Stability and Accelerated Endosomal Escape with Reduced IFNα-Associated Immune Response†
Hiroyasu Takemoto
Department of Materials Engineering, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan) http://www.bmw.t.u-tokyo.ac.jp/
Search for more papers by this authorCorresponding Author
Dr. Kanjiro Miyata
Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan)
Kanjiro Miyata, Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan)
Kazunori Kataoka, Department of Materials Engineering, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan) http://www.bmw.t.u-tokyo.ac.jp/
Search for more papers by this authorShota Hattori
Department of Bioengineering, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan)
Search for more papers by this authorDr. Takehiko Ishii
Department of Bioengineering, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan)
Search for more papers by this authorTomoya Suma
Department of Bioengineering, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan)
Search for more papers by this authorSatoshi Uchida
Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan)
Search for more papers by this authorDr. Nobuhiro Nishiyama
Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503 (Japan)
Search for more papers by this authorCorresponding Author
Dr. Kazunori Kataoka
Department of Materials Engineering, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan) http://www.bmw.t.u-tokyo.ac.jp/
Kanjiro Miyata, Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan)
Kazunori Kataoka, Department of Materials Engineering, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan) http://www.bmw.t.u-tokyo.ac.jp/
Search for more papers by this authorHiroyasu Takemoto
Department of Materials Engineering, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan) http://www.bmw.t.u-tokyo.ac.jp/
Search for more papers by this authorCorresponding Author
Dr. Kanjiro Miyata
Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan)
Kanjiro Miyata, Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan)
Kazunori Kataoka, Department of Materials Engineering, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan) http://www.bmw.t.u-tokyo.ac.jp/
Search for more papers by this authorShota Hattori
Department of Bioengineering, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan)
Search for more papers by this authorDr. Takehiko Ishii
Department of Bioengineering, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan)
Search for more papers by this authorTomoya Suma
Department of Bioengineering, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan)
Search for more papers by this authorSatoshi Uchida
Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan)
Search for more papers by this authorDr. Nobuhiro Nishiyama
Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503 (Japan)
Search for more papers by this authorCorresponding Author
Dr. Kazunori Kataoka
Department of Materials Engineering, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan) http://www.bmw.t.u-tokyo.ac.jp/
Kanjiro Miyata, Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan)
Kazunori Kataoka, Department of Materials Engineering, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan) http://www.bmw.t.u-tokyo.ac.jp/
Search for more papers by this authorThis research is supported by the Japan Society for the Promotion of Science (JSPS) through the “Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program),” and Health and Labour Sciences Research Grants Research on Medical Device Development, Ministry of Health, Labour and Welfare. H.T. thanks the Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists (JSPS).
Graphical Abstract
An siRNA conjugate is based on an acid-labile maleic acid amide linkage for programmed transfer of siRNA from the endosome to the cytosol and siRNA release in the cell interior. The procedure relies on reversible stability in response to endosomal acidic pH value. The complexed polyionic conjugate achieved gene silencing in cultured cancerous cells with negligible side effects.
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References
- 1
- 1aS. M. Elbashir, J. Harborth, W. Lendeckel, A. Yalcin, K. Weber, T. Tuschl, Nature 2001, 411, 494–498;
- 1bJ. C. Burnett, J. J. Rossi, Chem. Biol. 2012, 19, 60–71.
- 2R. L. Kanasty, K. A. Whitehead, A. J. Vegas, D. G. Anderson, Mol. Ther. 2012, 20, 513–524.
- 3
- 3aD. B. Rozema, D. L. Lewis, D. H. Wakefield, S. C. Wong, J. J. Klein, P. L. Roesch, S. L. Bertin, T. W. Reppen, Q. Chu, A. V. Blokhin, J. E. Hagstrom, J. A. Wolf, Proc. Natl. Acad. Sci. USA 2007, 104, 12982–12987;
- 3bY. Singh, P. Murat, E. Defrancq, Chem. Soc. Rev. 2010, 39, 2054–2070;
- 3cM. R. Alam, X. Ming, M. Fisher, J. G. Lackey, K. G. Rajeev, M. Manoharan, R. L. Juliano, Bioconjugate Chem. 2011, 22, 1673–1681;
- 3dS. K. Lee, A. Siefert, J. Beloor, T. M. Fahmy, P. Kumar, Methods Enzymol. 2012, 502, 91–122.
- 4
- 4aA.-L. Bolcato-Bellemin, M.-E. Bonnet, G. Creusat, P. Erbacher, J.-P. Behr, Proc. Natl. Acad. Sci. USA 2007, 104, 16050–16055;
- 4bH. Mok, S. H. Lee, J. W. Park, T. G. Park, Nat. Mater. 2010, 9, 272–278;
- 4cH. Takemoto, A. Ishii, K. Miyata, M. Nakanishi, M. Oba, T. Ishii, Y. Yamasaki, N. Nishiyama, K. Kataoka, Biomaterials 2010, 31, 8097–8105;
- 4dC. A. Hong, S. H. Lee, J. S. Kim, J. W. Park, K. H. Bae, H. Mok, T. G. Park, H. Lee, J. Am. Chem. Soc. 2011, 133, 13914–13917;
- 4eS. J. Lee, M. S. Huh, S. Y. Lee, S. Min, S. Lee, H. Koo, J. U. Chu, K. E. Lee, H. Jeon, Y. Choi, K. Choi, Y. Byun, S. Y. Jeong, K. Park, K. Kim, I. C. Kwon, Angew. Chem. 2012, 124, 7315–7319; Angew. Chem. Int. Ed. 2012, 51, 7203–7207.
- 5A. Judge, I. MacLachlan, Hum. Gene Ther. 2008, 19, 111–124.
- 6
- 6aC. Troiber, E. Wagner, Bioconjugate Chem. 2011, 22, 1737–1752;
- 6bJ. Nguyen, F. C. Szoka, Acc. Chem. Res. 2012, 45, 1153–1162.
- 7
- 7aD. B. Rozema, K. Ekena, D. L. Lewis, A. G. Loomis, J. A. Wolff, Bioconjugate Chem. 2003, 14, 51–57;
- 7bS. Guo, Y. Huang, Q. Jiang, Y. Sun, L. Deng, Z. Liang, Q. Du, J. Xing, Y. Zhao, P. C. Wang, A. Dong, X.-J. Liang, ACS Nano 2010, 4, 5505–5511.
- 8Y. Lee, K. Miyata, M. Oba, T. Ishii, S. Fukushima, M. Han, H. Koyama, N. Nishiyama, K. Kataoka, Angew. Chem. 2008, 120, 5241–5244; Angew. Chem. Int. Ed. 2008, 47, 5163–5166.
- 9K. Miyata, M. Oba, M. Nakanishi, S. Fukushima, Y. Yamasaki, H. Koyama, N. Nishiyama, K. Kataoka, J. Am. Chem. Soc. 2008, 130, 16287–16294.
- 10H. Takemoto, K. Miyata, T. Ishii, S. Hattori, S. Osawa, N. Nishiyama, K. Kataoka, Bioconjugate Chem. 2012, 23, 1503–1506.
- 11J. DeRouchey, C. Schmidt, G. F. Walker, C. Koch, C. Plank, E. Wagner, J. O. Radler, Biomacromolecules 2008, 9, 724–732.
- 12
- 12aM. J. Palte, R. T. Raines, J. Am. Chem. Soc. 2012, 134, 6218–6223;
- 12bM. Zheng, D. Librizzi, A. Kılıç, Y. Liu, H. Renz, O. M. Merkel, T. Kissel, Biomaterials 2012, 33, 6551–6558.
- 13K. Whitehead, G. Sahay, G. Z. Li, K. T. Love, C. A. Alabi, M. Ma, C. Zurenko, W. Querbes, R. S. Langer, D. G. Anderson, Mol. Ther. 2011, 19, 1688–1694.
- 14J. Turco, H. H. Winker, Infect. Immun. 1982, 35, 783–791.
- 15
- 15aA. D. Judge, M. Robbins, I. Tavakoli, J. Levi, L. Hu, A. Fronda, E. Ambegia, K. McClintock, I. MacLachlan, J. Clin. Invest. 2009, 119, 661–673;
- 15bK. Strebhardt, Nat. Rev. Drug Discovery 2010, 9, 643–660.
