Abstract
Delivery is a key issue in development of clinically relevant RNAi therapeutics. Polymeric nanoparticles formed by self-assembly of polycations with siRNA can be used for extracellular delivery, cellular uptake and intracellular trafficking as a strategy to improve the therapeutic potential of siRNA. This chapter describes a chitosan-based nanoparticle system for in vitro and in vivo transfection of siRNA into cells. The method exploits the mucoadhesive and mucopermeable properties of this cationic polysaccharide to deliver siRNA across mucosal epithelium and provides a platform for targeting human diseases with RNAi therapeutics.
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Fire, A., et al. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806–811.
Elbashir, S. M., et al. (2001). Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494–498.
Pouton, C. W. and Seymour, L. W. (2001) Key issues in non-viral gene delivery. Adv. Drug Deliv. Rev. 46, 187–203.
Elouahabi, A. and Ruysschaert, J. M. (2005) Formation and intracellular trafficking of lipoplexes and polyplexes. Mol. Ther. 11, 336–347.
Howard, K. A., et al. (2006). RNA Interference in vitro and in vivo using a novel chitosan/siRNA nanoparticle system. Mol. Ther. 14, 476–484.
Liu, X., et al. (2007). The influence of polymeric properties on chitosan/siRNA nanoparticle formulation and gene silencing. Biomaterials 28, 1280–1288.
Soane, R. J., et al. (1999). Evaluation of the clearance characteristics of bioadhesive systems in humans. Int. J. Pharm. 178, 55–65.
Artursson, P., Lindmark, T., Davis, S. S. and Illum, L. (1994). Effect of chitosan on the permeability of monolayers of intestinal epithelial cells (Caco-2). Pharm. Res. 11, 1358–1361.
Feng, J., Zhao, L. and Yu, Q. (2004). Receptor-mediated stimulatory effect of oligochitosan in macrophages. Biochem. Biophys. Res. Commun. 317, 414–420.
Howard, K. A., et al. (2009). Knockdown in peritoneal macrophages as an anti-inflammatory treatement in a murine arthritic model. Mol. Ther. 17, 162–168.
Andersen, M. O., et al. (2008). Delivery of siRNA from lyophilized polymeric surfaces. Biomaterials 29, 506–512.
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© 2009 Humana Press, a part of Springer Science+Business Media, LLC
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Andersen, M.Ø., Howard, K.A., Kjems, J. (2009). RNAi Using a Chitosan/siRNA Nanoparticle System: In Vitro and In Vivo Applications. In: Rondinone, C., Reidhaar-Olson, J. (eds) Therapeutic Applications of RNAi. Methods in Molecular Biology™, vol 555. Humana Press. https://doi.org/10.1007/978-1-60327-295-7_6
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DOI: https://doi.org/10.1007/978-1-60327-295-7_6
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Publisher Name: Humana Press
Print ISBN: 978-1-60327-294-0
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