Role of RNAi in Cancer

  • Kewal K. Jain
Chapter

Abstract

RNA interference (RNAi) is an ancient natural antiviral mechanism that directs silencing of gene expression in a sequence-specific manner. It is one of the technologies for suppression of gene function of which the best known involves the use of antisense oligonucleotides. RNAi involves the use of a double-stranded RNA (dsRNA). Once in the cell, the dsRNAs are processed into short, 21–23 nucleotide dsRNAs termed small interfering RNAs (siRNAs) that are used in a sequence-specific manner to recognize and destroy complementary RNAs. There are several classes of naturally occurring small RNA species, including siRNAs, repeat-associated siRNAs (rasiRNAs), and microRNAs (miRNAs); the last type is described in Chap. 13. Basics of RNAi and details of RNAi-based therapeutics are described in detail in a special report on this topic (Jain 2013).

Keywords

Cholesterol Toxicity Sarcoma Encapsulation Nucleoside 

References

  1. Aigner A. Transkingdom RNA, interference (tkRNAi) as a new delivery tool for therapeutic RNA. Expert Opin Biol Ther 2009;9:1533-42.Google Scholar
  2. Beck AK, Pass HI, Carbone M, Yang H. Ranpirnase as a potential antitumor ribonuclease treatment for mesothelioma and other malignancies. Future Oncol 2008;4:341-9.CrossRefGoogle Scholar
  3. Berezhna SY, Supekova L, Supek F, et al. siRNA in human cells selectively localizes to target RNA sites. PNAS 2006;103:7682-7.Google Scholar
  4. Chen XP, Wang Q, Guan J, et al. Reversing multidrug resistance by RNA interference through the suppression of MDR1 gene in human hepatoma cells. World J Gastroenterol 2006;12:3332-7.Google Scholar
  5. Davis ME, Zuckerman JE, Choi CH, et al. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 2010;464:1067-70.CrossRefGoogle Scholar
  6. de Martimprey H, Bertrand JR, Fusco A, et al. siRNA nanoformulation against the ret/PTC1 junction oncogene is efficient in an in vivo model of papillary thyroid carcinoma. Nucleic Acids Res 2008;36:e2.Google Scholar
  7. Gomes-da-Silva LC, Santos AO, Bimbo LM, et al. Toward a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment. Int J Pharm 2012;434:9-19.CrossRefGoogle Scholar
  8. Guo S, Tschammer N, Mohammed S, Guo P. Specific Delivery of Therapeutic RNAs to Cancer Cells via the Dimerization Mechanism of PHI29 Motor pRNA. Human Gene Therapy 2005;16:1097-1109.CrossRefGoogle Scholar
  9. Halder J, Kamat AA, Landen CN Jr, et al. Focal Adhesion Kinase Targeting Using In vivo Short Interfering RNA Delivery in Neutral Liposomes for Ovarian Carcinoma Therapy. Clin Cancer Res 2006;12:4916-24.CrossRefGoogle Scholar
  10. Heidel JD, Yu Z, Liu J, et al. Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA. PNAS 2007a;104:5715-21.CrossRefGoogle Scholar
  11. Heidel JD, Liu JY, Yen Y, et al. Potent siRNA inhibitors of ribonucleotide reductase subunit RRM2 reduce cell proliferation in vitro and in vivo. Clin Cancer Res 2007b;13:2207-15.CrossRefGoogle Scholar
  12. Jain KK. RNAi: technologies, markets and companies. Jain PharmaBiotech Publications. Basel, Switzerland, 2013.Google Scholar
  13. Jin W, Cote GJ. Enhancer-dependent splicing of FGFR1 alpha-exon is repressed by RNA interference-mediated down-regulation of SRp55. Cancer Res 2004;64:8901-5.CrossRefGoogle Scholar
  14. Judge AD, Bola G, Lee AC, MacLachlan I. Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo. Mol Ther 2006;13:494-505.CrossRefGoogle Scholar
  15. Kawasaki H, Taira K. Induction of DNA methylation and gene silencing by short interfering RNAs in human cells. Nature 2004;431:211-7.CrossRefGoogle Scholar
  16. Khaled A, Guo S, Li F, Guo P. Controllable Self-Assembly of Nanoparticles for Specific Delivery of Multiple Therapeutic Molecules to Cancer Cells Using RNA Nanotechnology. Nano Lett 2005;5:1797-1808.CrossRefGoogle Scholar
  17. Krühn A, Wang A, Fruehauf JH, Lage H. Delivery of short hairpin RNAs by transkingdom RNA interference modulates the classical ABCB1-mediated multidrug-resistant phenotype of cancer cells. Cell Cycle 2009;8:3349-54.CrossRefGoogle Scholar
  18. Lee I. Ranpirnase (Onconase), a cytotoxic amphibian ribonuclease, manipulates tumour physiological parameters as a selective killer and a potential enhancer for chemotherapy and radiation in cancer therapy. Expert Opin Biol Ther 2008;8:813-27.CrossRefGoogle Scholar
  19. MacDiarmid JA, Amaro-Mugridge NB, Madrid-Weiss J, et al. Sequential treatment of drug-resistant tumors with targeted minicells containing siRNA or a cytotoxic drug. Nat Biotechnol 2009;27:643-51.CrossRefGoogle Scholar
  20. McNamara JO 2nd, Andrechek ER, Wang Y, et al. Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat Biotechnol 2006;24:1005-15.CrossRefGoogle Scholar
  21. Merritt WM, Lin WG, Han LY, et al. Dicer, Drosha, and Outcomes in Patients with Ovarian Cancer. NEJM 2008;359:2641-50.CrossRefGoogle Scholar
  22. Nguyen TA, Fruehauf JH. Transkingdom RNA interference (tkRNAi): a novel method to induce therapeutic gene silencing. Methods Mol Biol 2009;514:27-34.CrossRefGoogle Scholar
  23. Pastor F, Kolonias D, Giangrande PH, Gilboa E. Induction of tumour immunity by targeted inhibition of nonsense-mediated mRNA decay. Nature 2010;465:227-30.CrossRefGoogle Scholar
  24. Pei DS, Di JH, Chen FF, Zheng JN. Oncolytic-adenovirus-expressed RNA interference for cancer therapy. Expert Opin Biol Ther 2010;10:1331-41.CrossRefGoogle Scholar
  25. Pille JY, Li H, Blot E, Bertrand JR, et al. Intravenous Delivery of Anti-RhoA Small Interfering RNA Loaded in Nanoparticles of Chitosan in Mice: Safety and Efficacy in Xenografted Aggressive Breast Cancer. Hum Gene Ther 2006;17:1019-26.CrossRefGoogle Scholar
  26. Pirollo KF, Rait A, Zhou Q, et al. Materializing the Potential of Small Interfering RNA via a Tumor-Targeting Nanodelivery System. Cancer Res 2007;67:2938-43.CrossRefGoogle Scholar
  27. Santel A, Aleku M, Keil O, et al. A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium. Gene Ther 2006;13:1222-34.CrossRefGoogle Scholar
  28. Santel A, Aleku M, Keil O, et al. RNA interference in the mouse vascular endothelium by systemic administration of siRNA-lipoplexes for cancer therapy. Gene Ther 2006a;13:1360-70.CrossRefGoogle Scholar
  29. Senzer N, Barve M, Kuhn J, et al. Phase I trial of “bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell” vaccine (FANG) in advanced cancer. Mol Ther 2012;20:679-86.CrossRefGoogle Scholar
  30. Siegwart DJ, Whitehead KA, Nuhn L, et al. Combinatorial synthesis of chemically diverse core-shell nanoparticles for intracellular delivery. PNAS 2011;108:12996-3001.CrossRefGoogle Scholar
  31. Wang SL, Yao HH, Qin ZH. Strategies for short hairpin RNA delivery in cancer gene therapy. Expert Opinion on Biological Therapy 2009;9:1357-68.CrossRefGoogle Scholar
  32. Wise-Draper TM, Wells SI. Efficient delivery of siRNA targeted against human papillomavirus oncogenes. BIOCHEMICA 2005;No.1:18-20.Google Scholar
  33. Xie Z, Wroblewska L, Prochazka L, et al. Multi-input RNAi-based logic circuit for identification of specific cancer cells. Science 2011;333:1307-11.CrossRefGoogle Scholar
  34. Yagi N, Manabe I, Tottori T, et al. A Nanoparticle System Specifically Designed to Deliver Short Interfering RNA Inhibits Tumor Growth In vivo. Cancer Res 2009;69:6531-8.CrossRefGoogle Scholar
  35. Zhao H, Ardelt B, Ardelt W, et al. The cytotoxic ribonuclease onconase targets RNA interference (siRNA). Cell Cycle 2008;7:1-4.Google Scholar
  36. Zhou J, Bobbin ML, Burnet JC, Rossi JJ. Current progress of RNA aptamer-based therapeutics. Frontiers in Genetics 2012;3:234.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Kewal K. Jain
    • 1
  1. 1.Jain PharmaBiotechBaselSwitzerland

Personalised recommendations