Summary
The intranasal administration of siRNA has opened new vistas in drug delivery and respiratory therapy. In this strategy, synthetic siRNA with or without chemical modifications can be applied intranasally. Various delivery vehicles have been tested and optimized. With a few exceptions, all promote significant uptake of siRNA into the lung tissue and offer protection against respiratory viruses such as respiratory syncytial virus (RSV), parainfluenza virus (PIV), and influenza virus. No major adverse immune reaction has been encountered. Nasally applied siRNA remains within the lung and does not have systemic access, as judged by its absence in other major organs such as the lung, liver, heart, and kidney. We provide techniques for using the nose as a specific route for siRNA delivery into the lung of laboratory animals, which has enormous potential for clinical applications.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E., and Mello, C. C. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans Nature 391, 806–811.
Elbashir, S. M., Martinez, J., Patkaniowska, A., Lendeckel, W., and Tuschl, T. (2001). Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate EMBO J. 20, 6877–6888.
Hammond, S. M., Bernstein, E., Beach, D., and Hannon, G. J. (2000). An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells Nature 404, 293–296.
Nykanen, A., Haley, B., and Zamore, P. D. (2001). ATP requirements and small interfering RNA structure in the RNA interference pathway Cell 107, 309–321.
Billy, E., Brondani, V., Zhang, H., Muller, U., and Filipowicz, W. (2001). Specific interference with gene expression induced by long, double-stranded RNA in mouse embryonal teratocarcinoma cell lines Proc. Natl. Acad. Sci. USA 98, 14428–14433.
Barik, S. (2004). Control of nonsegmented negative-strand RNA virus replication by siRNA Virus Res. 102, 27–35.
Barik, S. (2005). Silence of the transcripts: RNA interference in medicine J. Mol. Med. 83,764–773.
Bitko, V., and Barik, S. (2007). Intranasal antisense therapy: Preclinical models with a clinical future? Curr. Opin. Mol. Ther. 9, 119–125.
Bitko, V., and Barik, S. (2001). Phenotypic silencing of cytoplasmic genes using sequence-specific double-stranded short interfering RNA and its application in the reverse genetics of wild type negative-strand RNA viruses BMC Microbiol. 1, 34.
Bitko, V., Musiyenko, A., Shulyayeva, O., and Barik, S. (2004). Inhibition of respiratory viruses by nasally administered siRNA Nat. Med. 11, 50–55.
Shin, D., Kim, S. I., Kim, M., and Park, M. (2006). Efficient inhibition of hepatitis B virus replication by small interfering RNAs targeted to the viral X gene in mice Virus Res. 119, 146–153.
Zender, L., Hutker, S., Liedtke, C., et al. (2003). Caspase 8 small interfering RNA prevents acute liver failure in mice Proc. Natl. Acad. Sci. USA 100, 7797–7802.
Morrissey, D. V., Lockridge, J. A., Shaw, L., et al. (2005). Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs Nat. Biotechnol. 23, 1002–1007.
Song, E., Lee, S. K., Wang, J., et al. (2003). RNA interference targeting Fas protects mice from fulminant hepatitis Nat. Med. 9, 347–351.
Palliser, D., Chowdhury, D., Wang, Q. Y., et al. (2006). An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection Nature 439, 89–94.
Bitko, V., Musiyenko, A., and Barik, S. (2007). Viral infection of the lungs through the eye J. Virol. 81, 783–790.
Banerjea, A., Li, M. J., Bauer, G., Remling, L., Lee, N. S., Rossi, J., and Akkina, R. (2003). Inhibition of HIV-1 by lentiviral vector-transduced siRNAs in T ly phocytes differentiated in SCID-hu mice and CD34+ progenitor cell-derived macrophages Mol. Ther. 8, 62–71.
Nigo, Y. I., Yamashita, M., Hirahara, K., et al. (2006). Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function Proc. Natl. Acad. Sci. USA 103, 2286–2291.
Khoury, M., Louis-Plence, P., Escriou, V., et al. (2006). Efficient new cationic liposome formulation for systemic delivery of small interfering RNA silencing tumor necrosis factor alpha in experimental arthritis Arthritis Rheum. 54, 1867–1877.
Landen, C. N., Merritt, W. M., Mangala, L. S., et al. (2006). Intraperitoneal delivery of liposomal siRNA for therapy of advanced ovarian cancer Cancer Biol. Ther. 5, 1708–1713.
Zhang, Y. A., Nemunaitis, J., Samuel, S. K., Chen, P., Shen, Y., and Tong, A. W. (2006). Antitumor activity of an oncolytic adenovirus-delivered oncogene small interfering RNA Cancer Res. 66, 9736–9743.
Rodriguez-Lebron, E., Denovan-Wright, E. M., Nash, K., Lewin, A. S., and Mandel, R. J. (2005). Intrastriatal rAAV-mediated delivery of anti-huntington shRNAs induces partial reversal of disease progression in R6/1 Huntington’s disease transgenic mice Mol. Ther. 12, 618–633.
Wang, Y. L., Liu, W., Wada, E., Murata, M., Wada, K., and Kanazawa, I. (2005). Clinico-pathological rescue of a model mouse of Huntington’s disease by siRNA Neurosci. Res. 53, 241–249.
Nakamura, H., Siddiqui, S. S., Shen, X., et al. (2004). RNA interference targeting transforming growth factor-beta type II receptor suppresses ocular inflammation and fibrosis Mol. Vis. 10, 703–711.
Tang, W., Yang, X., Maguire, A. M., Bennett, J., and Tolentino, M. J. (2003). Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in a mouse model Mol. Vis. 9, 210–216.
Reich, S. J., Fosnot, J., Kuroki, A., et al. (2003). Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in a mouse model Mol. Vis. 9, 210–216.
Shen, J., Samul, R., Silva, R. L., et al. (2006). Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1 Gene Ther. 13, 225–234.
Rana, T. M. (2007). Illuminating the silence: Understanding the structure and function of small RNAs Nat. Rev. Mol. Cell. Biol. 8, 23–36.
Dorn, G., Patel, S., Wotherspoon, G., et al. (2004). siRNA relieves chronic neuropathic pain Nucleic Acids Res. 32, e49.
Hassani, Z., Lemkine, G. F., Erbacher, P., et al. (2005). Lipid-mediated siRNA delivery down-regulates exogenous gene expression in the mouse brain at picomolar levels J. Gene Med. 7, 198–207.
Sioud, M., and Sorensen, D. R. (2003). Cationic liposome-mediated delivery of siRNAs in adult mice Biochem. Biophys. Res. Commun. 312,1220–1225.
Massaro, D., Massaro, G. D., and Clerch, L. B. (2004). Noninvasive delivery of small inhibitory RNA and other reagents to pulmonary alveoli in mice Am. J. Physiol. Lung. Cell Mol. Physiol. 287, L1066–L1070.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Bitko, V., Barik, S. (2008). Nasal Delivery of siRNA. In: Barik, S. (eds) RNAi. Methods in Molecular Biology™, vol 442. Humana Press. https://doi.org/10.1007/978-1-59745-191-8_6
Download citation
DOI: https://doi.org/10.1007/978-1-59745-191-8_6
Publisher Name: Humana Press
Print ISBN: 978-1-58829-874-4
Online ISBN: 978-1-59745-191-8
eBook Packages: Springer Protocols