Summary
The use of siRNA in vivo as well as in animal models has become more widespread in recent years, leading to further questions as to the best mode of delivery that will achieve optimal knockdown. While the exact mechanism of siRNA uptake at a cellular level has yet to be fully elucidated, various delivery techniques are being researched, including the use of viral vectors of shRNA, liposome encapsulations, and hydrodynamic delivery of naked siRNA. We describe the use of hydrodynamic administration as a technique to deliver, in vivo, naked siRNA constructs into experimental animals as a method of transient gene knockdown. This method may prove useful in situations where knockout animals do not exist, or to determine the effect of gene knockdown at specific time points during an experiment.
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
Liu, F., Song, Y. K., and Liu, D. (1999). Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA Gene Ther. 6, 1258–1266.
Song, E., Lee, S. K., Wang, J., et al. (2003). RNA interference targeting Fas protects mice from fulminant hepatitis Nat. Med. 9, 347–351.
Wesche-Soldato, D. E., Chung, C. S., Lomas-Neira, J., Doughty, L. A., Gregory, S. H., and Ayala, A. (2005). In vivo delivery of caspase 8 or Fas siRNA improves the survival of septic mice Blood 106, 2295–2301.
Sledz, C. A., Holko, M., de Veer, M. J., Silverman, R. H., and Williams, B. R. (2003). Activation of the interferon system by short-interfering RNAs Nat. Cell Biol. 5, 834–839.
Bridge, A. J., Pebernard, S., Ducraux, A., Nicoulaz, A.-L., and Iggo, R. (2003). Induction of an interferon response by RNAi vectors in mammalian cells Nat. Genet. 34, 263–264.
Kariko, K., Bhuyan, P., Capodici, J., and Weissman, D. (2004). Small interfering RNAs mediate sequence-independent gene suppression and induce immune activation by signaling through Toll-like receptor 3 J. Immunol. 172, 6545–6549.
Perl, M., Chung, C. S., Lomas-Neira, J., et al. (2005). Silencing of Fas- but not caspase-8 in lung epithelial cells ameliorates experimental acute lung injury Am. J. Pathol. 167, 1545–1559.
Heidel, J. D., Siwen, H., Liu, X. F., Triche, T. J., and Davis, M. E. (2004). Lack of IFN response in animals to naked siRNAs Nat. Biotechnol. 22, 1579–1582.
Sebestyen, M. G., Budker, V. G., Budker, T., et al. (2006). Mechanism of plasmid delivery by hydrodynamic tail vein injection. I. Hepatocyte uptake of various molecules J. Gene Med. 8, 852–873.
Feng, D. M., He, C. X., Miao, C. Y., et al. (2004). Conditions affecting hydrodynamics-based gene delivery into mouse liver in vivo Clin. Exp. Pharmacol. Physiol. 31, 850–855.
Ayala, A., Herdon, C. D., Lehman, D. L., Ayala, C. A., and Chaudry, I. H. (1996). Differential induction of apoptosis in lymphoid tissues during sepsis: Variation in onset, frequency, and the nature of the mediators Blood 87, 4261–4275.
Okabe, M., Ikawa, M., Kominami, I., Nakanishi, T., and Nishimune, Y. (1997). “Green mice” as a source of ubiquitous green cells FEBS Lett. 407, 313–319.
Levy, D. E. (2002). Whence interferon? Variety in the production of interferon in response to viral infection J. Exp. Med. 195, F15–F18.
Asselin-Paturel, C., Boonstra, A., Dalod, M., et al. (2001). Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology Nat. Immun. 2, 1144–1150.
Jackson, A. L., Bartz, S. R., Schelter, J., et al. (2003). Expression profiling reveals off-target gene regulation by RNAi Nat. Biotechnol. 21, 635–637.
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
Wesche-Soldato, D.E., Lomas-Neira, J., Perl, M., Chung, CS., Ayala, A. (2008). Hydrodynamic Delivery of siRNA in a Mouse Model of Sepsis. In: Barik, S. (eds) RNAi. Methods in Molecular Biology™, vol 442. Humana Press. https://doi.org/10.1007/978-1-59745-191-8_5
Download citation
DOI: https://doi.org/10.1007/978-1-59745-191-8_5
Publisher Name: Humana Press
Print ISBN: 978-1-58829-874-4
Online ISBN: 978-1-59745-191-8
eBook Packages: Springer Protocols