Table of Contents
ISRN Pharmaceutics
Volume 2012 (2012), Article ID 407154, 7 pages
http://dx.doi.org/10.5402/2012/407154
Research Article

Modulating Anti-MicroRNA-21 Activity and Specificity Using Oligonucleotide Derivatives and Length Optimization

1Department of Neurochemistry, Stockholm University, Svante Arrhenius väg 21A, 106 92 Stockholm, Sweden
2GE Healthcare Bio-Sciences, Björkgatan 30, 751 84 Uppsala, Sweden
3Integrated DNA Technologies, 1710 Commercial Park, Coralville, IA 52241, USA
4Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, 5230 Odense M, Denmark
5Department of Laboratory Medicine, Karolinska Institute, Hälsovägen 7, 141 86 Huddinge, Sweden

Received 27 September 2011; Accepted 17 October 2011

Academic Editors: R. Benhida and R. Teng

Copyright © 2012 Andrés Muñoz-Alarcón et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. Fire, S. Xu, M. K. Montgomery, S. A. Kostas, S. E. Driver, and C. C. Mello, “Potent and specific genetic interference by double-stranded RNA in caenorhabditis elegans,” Nature, vol. 391, no. 6669, pp. 806–811, 1998. View at Publisher · View at Google Scholar · View at Scopus
  2. S. M. Elbashir, J. Harborth, W. Lendeckel, A. Yalcin, K. Weber, and T. Tuschl, “Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells,” Nature, vol. 411, no. 6836, pp. 494–498, 2001. View at Publisher · View at Google Scholar · View at Scopus
  3. N. J. Caplen, S. Parrish, F. Imani, A. Fire, and R. A. Morgan, “Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 17, pp. 9742–9747, 2001. View at Publisher · View at Google Scholar · View at Scopus
  4. G. A. Calin and C. M. Croce, “MicroRNA signatures in human cancers,” Nature Reviews Cancer, vol. 6, no. 11, pp. 857–866, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. O. A. Kent and J. T. Mendell, “A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes,” Oncogene, vol. 25, no. 46, pp. 6188–6196, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. A. Esquela-Kerscher and F. J. Slack, “Oncomirs—microRNAs with a role in cancer,” Nature Reviews Cancer, vol. 6, no. 4, pp. 259–269, 2006. View at Publisher · View at Google Scholar · View at Scopus
  7. C. Esau, S. Davis, S. F. Murray et al., “miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting,” Cell Metabolism, vol. 3, no. 2, pp. 87–98, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. J. Krutzfeldt, N. Rajewsky, R. Braich et al., “Silencing of microRNAs in vivo with ‘antagomirs’,” Nature, vol. 438, no. 7068, pp. 685–689, 2005. View at Publisher · View at Google Scholar · View at Scopus
  9. N. S. Wickramasinghe, T. T. Manavalan, S. M. Dougherty, K. A. Riggs, Y. Li, and C. M. Klinge, “Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells,” Nucleic Acids Research, vol. 37, no. 8, pp. 2584–2595, 2009. View at Publisher · View at Google Scholar · View at Scopus
  10. S. Dong, Y. Cheng, J. Yang et al., “MicroRNA expression signature and the role of MicroRNA-21 in the early phase of acute myocardial infarction,” Journal of Biological Chemistry, vol. 284, no. 43, pp. 29514–29525, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. J. A. Chan, A. M. Krichevsky, and K. S. Kosik, “MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells,” Cancer Research, vol. 65, no. 14, pp. 6029–6033, 2005. View at Publisher · View at Google Scholar · View at Scopus
  12. C. Roldo, E. Missiaglia, J. P. Hagan et al., “MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior,” Journal of Clinical Oncology, vol. 24, no. 29, pp. 4677–4684, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. M. L. Si, S. Zhu, H. Wu, Z. Lu, F. Wu, and Y. Y. Mo, “miR-21-mediated tumor growth,” Oncogene, vol. 26, no. 19, pp. 2799–2803, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. F. Meng, R. Henson, H. Wehbe-Janek, K. Ghoshal, S. T. Jacob, and T. Patel, “MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer,” Gastroenterology, vol. 133, no. 2, pp. 647–658, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. G. Hutvagner, M. J. Simard, C. C. Mello, and P. D. Zamore, “Sequence-specific inhibition of small RNA function,” PLoS Biology, vol. 2, no. 4, p. E98, 2004. View at Publisher · View at Google Scholar · View at Scopus
  16. J. Wengel, “Synthesis of 30-C- and 40-C-branched oligonucleotides and the development of locked nucleic acid (LNA),” Accounts of Chemical Research, vol. 32, no. 4, pp. 301–310, 1999. View at Publisher · View at Google Scholar · View at Scopus
  17. J. Micklefield, “Backbone modification of nucleic acids: synthesis, structure and therapeutic applications,” Current Medicinal Chemistry, vol. 8, no. 10, pp. 1157–1179, 2001. View at Google Scholar · View at Scopus
  18. J. Kurreck, “Antisense technologies: improvement through novel chemical modifications,” European Journal of Biochemistry, vol. 270, no. 8, pp. 1628–1644, 2003. View at Publisher · View at Google Scholar · View at Scopus
  19. S. M. Freier and K. H. Altmann, “The ups and downs of nucleic acid duplex stability: structure-stability studies on chemically-modified DNA:RNA duplexes,” Nucleic Acids Research, vol. 25, no. 22, pp. 4429–4443, 1997. View at Google Scholar · View at Scopus
  20. A. A. Koshkin, S. K. Singh, P. Nielsen et al., “LNA (Locked Nucleic Acids): synthesis of the adenine, cytosine, guanine, 5-methylcytosine, thymine and uracil bicyclonucleoside monomers, oligomerisation, and unprecedented nucleic acid recognition,” Tetrahedron, vol. 54, no. 14, pp. 3607–3630, 1998. View at Publisher · View at Google Scholar · View at Scopus
  21. B. Vester and J. Wengel, “LNA (Locked Nucleic Acid): high-affinity targeting of complementary RNA and DNA,” Biochemistry, vol. 43, no. 42, pp. 13233–13241, 2004. View at Google Scholar · View at Scopus
  22. J. S. Jepsen and J. Wengel, “LNA-antisense rivals siRNA for gene silencing,” Current Opinion in Drug Discovery and Development, vol. 7, no. 2, pp. 188–194, 2004. View at Google Scholar · View at Scopus
  23. H. Orum and J. Wengel, “Locked nucleic acids: a promising molecular family for gene-function analysis and antisense drug development,” Current Opinion in Molecular Therapeutics, vol. 3, no. 3, pp. 239–243, 2001. View at Google Scholar · View at Scopus
  24. N. Langkjaer, A. Pasternak, and J. Wengel, “UNA (unlocked nucleic acid): a flexible RNA mimic that allows engineering of nucleic acid duplex stability,” Bioorganic and Medicinal Chemistry, vol. 17, no. 15, pp. 5420–5425, 2009. View at Publisher · View at Google Scholar · View at Scopus
  25. S. Akhtar and R. L. Juliano, “Cellular uptake and intracellular fate of antisense oligonucleotides,” Trends in Cell Biology, vol. 2, no. 5, pp. 139–144, 1992. View at Google Scholar · View at Scopus
  26. P. Guterstam, M. Lindgren, H. Johansson et al., “Splice-switching efficiency and specificity for oligonucleotides with locked nucleic acid monomers,” Biochemical Journal, vol. 412, no. 2, pp. 307–313, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. W. M. Flanagan, A. Kothavale, and R. W. Wagner, “Effects of oligonucleotide length, mismatches and mRNA levels on C-5 propyne-modified antisense potency,” Nucleic Acids Research, vol. 24, no. 15, pp. 2936–2941, 1996. View at Publisher · View at Google Scholar · View at Scopus
  28. R. E. Lanford, E. S. Hildebrandt-Eriksen, A. Petri et al., “Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection,” Science, vol. 327, no. 5962, pp. 198–201, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. J. Elmén, M. Lindow, S. Schütz et al., “LNA-mediated microRNA silencing in non-human primates,” Nature, vol. 452, no. 7189, pp. 896–899, 2008. View at Publisher · View at Google Scholar
  30. E. E. Swayze, A. M. Siwkowski, E. V. Wancewicz et al., “Antisense oligonucleotides containing locked nucleic acid improve potency but cause significant hepatotoxicity in animals,” Nucleic Acids Research, vol. 35, no. 2, pp. 687–700, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. Q. Zhao, S. Matson, C. J. Herrera, E. Fisher, H. Yu, and A. M. Krieg, “Comparison of cellular binding and uptake of antisense phosphodiester, phosphorothioate, and mixed phosphorothioate and methylphosphonate oligonucleotides,” Antisense Research and Development, vol. 3, no. 1, pp. 53–66, 1993. View at Google Scholar · View at Scopus
  32. K. A. Lennox, J. L. Sabel, M. J. Johnson et al., “Characterization of modified antisense oligonucleotides in Xenopus laevis embryos,” Oligonucleotides, vol. 16, no. 1, pp. 26–42, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. D. A. Brown, S. H. Kang, S. M. Gryaznov et al., “Effect of phosphorothioate modification of oligodeoxynucleotides on specific protein binding,” Journal of Biological Chemistry, vol. 269, no. 43, pp. 26801–26805, 1994. View at Google Scholar · View at Scopus
  34. K. A. Lennox and M. A. Behlke, “A direct comparison of anti-microRNA oligonucleotide potency,” Pharmaceutical Research, vol. 27, no. 9, pp. 1788–1799, 2010. View at Publisher · View at Google Scholar · View at Scopus