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Systemic Delivery of Synthetic siRNAs

  • Dag R. Sørensen
  • Mouldy Sioud
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 629)

Abstract

RNA interference is a biological process for gene silencing that can be harnessed for the development of new drugs. However, a major obstacle to the use of small interfering RNAs (siRNAs) as therapeutics is their delivery across the plasma membrane of cells in vivo. A range of solutions for this challenge have been described, including cationic lipids, high-pressure injection, viral vectors, and chemical modifications of the siRNAs. This chapter describes cationic lipid delivery of siRNAs to adult mice.

Key words

RNA interference siRNA cationic lipids 

References

  1. 1.
    Sioud, M. (2001) Nucleic acid enzymes as a novel generation of anti-gene agents. Curr Mol Med, 1, 575–588.PubMedCrossRefGoogle Scholar
  2. 2.
    Behlke, M.A. (2006) Progress towards in vivo use of siRNAs. Mol Ther, 13, 644–666.PubMedCrossRefGoogle Scholar
  3. 3.
    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.PubMedCrossRefGoogle Scholar
  4. 4.
    Elbashir, S.M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., and Tuschl, T. (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 411, 494–498.PubMedCrossRefGoogle Scholar
  5. 5.
    Sioud, M. (2004) Therapeutic siRNAs. Trends Pharmacol Sci, 25, 22–28.PubMedCrossRefGoogle Scholar
  6. 6.
    Templeton, S.N. (2002) Liposomal delivery of nucleic acids in vivo. DNA Cell Biol, 21, 859–867.Google Scholar
  7. 7.
    Sørensen, D.R., Leirdal, M., and Sioud, M. (2003) Gene silencing by systemic delivery of synthetic siRNAs in adult mice. J Mol Biol, 327, 761–766.PubMedCrossRefGoogle Scholar
  8. 8.
    Morrissey, D.V., Lockridge, J.A., Shaw, L., Blanchard, K., Jensen, K., Breen, W., Hartsough, K., Machemer, L., Radka, S., Jadhav, V., Vaish, N., Zinnen, S., Vargeese, C., Bowman, K., Shaffer, C.S., Jeffs, L.B., Judge, A., MacLachlan, I., and Polisky, B. (2005) Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat Biotechnol, 23, 1002–1100.PubMedCrossRefGoogle Scholar
  9. 9.
    Sioud, M. (2005) On the delivery of small interfering RNAs into mammalian cells. Expert Opin Drug Deliv, 2, 639–651.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Dag R. Sørensen
    • 1
  • Mouldy Sioud
    • 2
  1. 1.Department of Comparative MedicineRadiumhospitalet-Rikshopitalet Universtity HospitalOsloNorway
  2. 2.Department of ImmunologyInstitute for Cancer Research, Rikshospitalet-Radiumhospitalet, Universtity HospitalOsloNorway

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