Advertisement

Activation and Deactivation of Antisense and RNA Interference Function with Light

  • Jeane M. Govan
  • Alexander Deiters
Chapter
Part of the RNA Technologies book series (RNATECHN)

Abstract

Oligonucleotides and oligonucleotide analogs have shown to be efficient tools for the silencing of gene expression in a wide range of cell lines and various model organisms. Such oligonucleotides include hairpin DNA, phosphorothioate DNA, morpholino oligonucleotides, peptide nucleic acids, and others. The common mode of action for all antisense agents is sequence-specific duplex formation with messenger RNA (mRNA), leading to the inhibition of translation and/or mRNA degradation and thus gene silencing. RNA interference (RNAi) is another tool to regulate gene expression through the site-specific degradation of mRNA. Several methods for the light regulation of oligonucleotide duplex formation and RNAi function have been developed, including the site-specific installation of light-removable protecting groups (caging groups) on nucleobases and photocleaveable inhibitor sequences. Light is an ideal external regulatory element as light irradiation can be easily and precisely controlled in timing, location, and amplitude. Through the engineering of light-activated oligonucleotides, their function can be regulated with high spatial and temporal resolution, allowing photochemical control of gene expression in biological systems with unprecedented precision.

Keywords

Antisense agents Gene expression Light regulation siRNA 

References

  1. Abdelgany A, Wood M, Beeson D (2007) Hairpin DNAzymes: a new tool for efficient cellular gene silencing. J Gene Med 9:727–738PubMedCrossRefGoogle Scholar
  2. Aboul-Fadl T (2005) Antisense oligonucleotides: the state of the art. Curr Med Chem 12:2193–2214PubMedCrossRefGoogle Scholar
  3. Adams SR, Tsien RY (1993) Controlling cell chemistry with caged compounds. Annu Rev Physiol 55:755–784PubMedCrossRefGoogle Scholar
  4. Ando H, Furuta T, Tsien RY et al (2001) Photo-mediated gene activation using caged RNA/DNA in zebrafish embryos. Nat Genet 28:317–325PubMedCrossRefGoogle Scholar
  5. Aravin A, Tuschl T (2005) Identification and characterization of small RNAs involved in RNA silencing. FEBS Lett 579:5830–5840PubMedCrossRefGoogle Scholar
  6. Banerjee A, Grewer C, Ramakrishnan L et al (2003) Toward the development of new photolabile protecting groups that can rapidly release bioactive compounds upon photolysis with visible light. J Org Chem 68:8361–8367PubMedCrossRefGoogle Scholar
  7. Blidner RA, Svoboda KR, Hammer RP et al (2008) Photoinduced RNA interference using DMNPE-caged 2′-deoxy-2′-fluoro substituted nucleic acids in vitro and in vivo. Mol Biosyst 4:431–440PubMedCrossRefGoogle Scholar
  8. Bolcato-Bellemin AL, Bonnet ME, Creusat G et al (2007) Sticky overhangs enhance siRNA-mediated gene silencing. Proc Natl Acad Sci USA 104:16050–16065PubMedCrossRefGoogle Scholar
  9. Cekaite L, Furset G, Hovig E et al (2007) Gene expression analysis in blood cells in response to unmodified and 2′-modified siRNAs reveals TLR-dependent and independent effects. J Mol Biol 365:90–108PubMedCrossRefGoogle Scholar
  10. Chen X, Dudgeon N, Shen L et al (2005) Chemical modification of gene silencing oligonucleotides for drug discovery and development. Drug Discov Today 10:587–593PubMedCrossRefGoogle Scholar
  11. Cheng K, Ye ZY, Guntaka RV et al (2006) Enhanced hepatic uptake and bioactivity of type alpha 1(I) collagen gene promoter-specific triplex-forming oligonucleotides after conjugation with cholesterol. J Pharmacol Exp Ther 317:797–805PubMedCrossRefGoogle Scholar
  12. Chiu YL, Rana TM (2003) SiRNA function in RNAi: a chemical modification analysis. RNA 9:1034–1048PubMedCrossRefGoogle Scholar
  13. Dean NM, Bennett CF (2003) Antisense oligonucleotide-based therapeutics for cancer. Oncogene 22:9087–9096PubMedCrossRefGoogle Scholar
  14. Deiters A (2009) Light activation as a method of regulating and studying gene expression. Curr Opin Chem Biol 13:678–686PubMedCrossRefGoogle Scholar
  15. Deiters A (2010) Principles and applications of the photochemical control of cellular processes. Chembiochem 11:47–53PubMedCrossRefGoogle Scholar
  16. Deiters A, Garner RA, Lusic H et al (2010) Photocaged morpholino oligomers for the light-regulation of gene function in zebrafish and Xenopus embryos. J Am Chem Soc 132:15644–15650PubMedCrossRefGoogle Scholar
  17. Dmochowski IJ, Tang XJ (2007) Taking control of gene expression with light-activated oligonucleotides. Biotechniques 43:161–171PubMedCrossRefGoogle Scholar
  18. Elbashir S, Harborth J, Lendeckel W et al (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494–498PubMedCrossRefGoogle Scholar
  19. Ellis-Davies GC (2007) Caged compounds: photorelease technology for control of cellular chemistry and physiology. Nat Methods 4:619–628PubMedCrossRefGoogle Scholar
  20. Forman J, Dietrich M, Monroe WT (2007) Photobiological and thermal effects of photoactivating UVA light doses on cell cultures. Photochem Photobiol Sci 6:649–658PubMedCrossRefGoogle Scholar
  21. Han G, Mokari T, Ajo-Franklin C et al (2008) Caged quantum dots. J Am Chem Soc 130:15811–15813PubMedCrossRefGoogle Scholar
  22. Harborth J, Elbashir SM, Vandenburgh K et al (2003) Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. Antisense Nucleic Acid Drug Dev 13:83–105PubMedCrossRefGoogle Scholar
  23. Heasman J (2002) Morpholino oligos: making sense of antisense? Dev Biol 243:209–214PubMedCrossRefGoogle Scholar
  24. Höbartner C, Silverman SK (2005) Modulation of RNA tertiary folding by incorporation of caged nucleotides. Angew Chem Int Ed 44:7305–7309CrossRefGoogle Scholar
  25. Ito H, Liang X, Nishioka H et al (2010) Construction of photoresponsive RNA for photoswitching RNA hybridization. Org Biomol Chem 8:5519–5524PubMedCrossRefGoogle Scholar
  26. Jain PK, Shah S, Friedman SH (2010) Patterning of gene expression using new photolabile groups applied to light activated RNAi. J Am Chem Soc 133:440–446PubMedCrossRefGoogle Scholar
  27. Jin Y, Liu S, Yu B et al (2010) Targeted delivery of antisense oligodeoxynucleotide by transferrin conjugated pH-sensitive lipopolyplex nanoparticles: a novel oligonucleotide-based therapeutic strategy in acute myeloid leukemia. Mol Pharm 7:196–206PubMedCrossRefGoogle Scholar
  28. Karkare S, Bhatnagar D (2006) Promising nucleic acid analogs and mimics: characteristic features and applications of PNA, LNA, and morpholino. Appl Microbiol Biotechnol 71:575–586PubMedCrossRefGoogle Scholar
  29. Kim SH, Jeong JH, Lee SH et al (2006) PEG conjugated VEGF siRNA for anti-angiogenic gene therapy. J Control Release 116:123–129PubMedCrossRefGoogle Scholar
  30. Kumar A, Yellepeddi VK, Davies GE et al (2010) Enhanced gene transfection efficiency by polyamidoamine (PAMAM) dendrimers modified with ornithine residues. Int J Pharm 392:294–303PubMedCrossRefGoogle Scholar
  31. Kwok T, Heinrich J, Jung-Shiu J et al (2009) Reduction of gene expression by a hairpin-loop structured oligodeoxynucleotide: alternative to siRNA and antisense. Biochim Biophys Acta 1790:1170–1178PubMedCrossRefGoogle Scholar
  32. Layzer JM, McCaffrey AP, Tanner AK et al (2004) In vivo activity of nuclease-resistant siRNAs. RNA 10:766–771PubMedCrossRefGoogle Scholar
  33. Lee HM, Larson DR, Lawrence DS (2009) Illuminating the chemistry of life: design, synthesis, and applications of "caged" and related photoresponsive compounds. ACS Chem Biol 4:409–427PubMedCrossRefGoogle Scholar
  34. Matsunaga D, Asanuma H, Komiyama M (2004) Photoregulation of RNA digestion by RNase H with azobenzene-tethered DNA. J Am Chem Soc 126:11452–11453PubMedCrossRefGoogle Scholar
  35. Mayer G, Heckel A (2006) Biologically active molecules with a "light switch". Angew Chem Int Ed 45:4900–4921CrossRefGoogle Scholar
  36. Meister G, Tuschl T (2004) Mechanisms of gene silencing by double-stranded RNA. Nature 431:343–349PubMedCrossRefGoogle Scholar
  37. Meng XM, Chen XY, Fu Y et al (2008) Photolysis of caged compounds and its applications to chemical biology. Prog Chem 20:2034–2044Google Scholar
  38. Mikat V, Heckel A (2007) Light-dependent RNA interference with nucleobase-caged siRNAs. RNA 13:2341–2347PubMedCrossRefGoogle Scholar
  39. Moulton HM, Moulton JD (2010) Morpholinos and their peptide conjugates: therapeutic promise and challenge for Duchenne muscular dystrophy. Biochim Biophys Acta 1798:2296–2303PubMedCrossRefGoogle Scholar
  40. Nguyen QN, Chavli RV, Marques JT et al (2006) Light controllable siRNAs regulate gene suppression and phenotypes in cells. Biochim Biophys Acta 1758:394–403PubMedCrossRefGoogle Scholar
  41. Nielsen PE, Egholm M, Berg RH et al (1991) Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science 254:1497–1500PubMedCrossRefGoogle Scholar
  42. Ouyang X, Shestopalov IA, Sinha S et al (2009) Versatile synthesis and rational design of caged morpholinos. J Am Chem Soc 131:13255–13269PubMedCrossRefGoogle Scholar
  43. Palma E, Cho MJ (2007) Improved systemic pharmacokinetics, biodistribution, and antitumor activity of CpG oligodeoxynucleotides complexed to endogenous antibodies in vivo. J Control Release 120:95–103PubMedCrossRefGoogle Scholar
  44. Priestman MA, Lawrence DS (2010) Light-mediated remote control of signaling pathways. Biochim Biophys Acta 1804:547–558PubMedCrossRefGoogle Scholar
  45. Richards JL, Tang X, Turetsky A et al (2008) RNA bandages for photoregulating in vitro protein synthesis. Bioorg Med Chem Lett 18:6255–6258PubMedCrossRefGoogle Scholar
  46. Richards JL, Seward GK, Wang YH et al (2010) Turning the 10–23 DNAzyme on and off with light. Chembiochem 11:320–324PubMedCrossRefGoogle Scholar
  47. Riggsbee CW, Deiters A (2010) Recent advances in the photochemical control of protein function. Trends Biotechnol 28:468–475PubMedCrossRefGoogle Scholar
  48. Shah S, Friedman SH (2007) Tolerance of RNA interference toward modifications of the 5′ antisense phosphate of small interfering RNA. Oligonucleotides 17:35–43PubMedCrossRefGoogle Scholar
  49. Shah S, Rangarajan S, Friedman SH (2005) Light activated RNA interference. Angew Chem Int Ed 44:1328–1332CrossRefGoogle Scholar
  50. Shah S, Jain PK, Kala A et al (2009) Light-activated RNA interference using double-stranded siRNA precursors modified using a remarkable regiospecificity of diazo-based photolabile groups. Nucleic Acids Res 37:4508–4517PubMedCrossRefGoogle Scholar
  51. Shestopalov IA, Sinha S, Chen JK (2007) Light-controlled gene silencing in zebrafish embryos. Nat Chem Biol 3:650–651PubMedCrossRefGoogle Scholar
  52. Schulte-Merker S, Lee KJ, McMahon AP et al (1997) The zebrafish organizer requires Chordin. Nature 387:862–863PubMedCrossRefGoogle Scholar
  53. Summerton JE (2007) Morpholino, siRNA, and S-DNA compared: impact of structure and mechanism of action on off-target effects and sequence specificity. Curr Top Med Chem 7:651–660PubMedCrossRefGoogle Scholar
  54. Tang X, Maegawa S, Weinberg ES et al (2007) Regulating gene expression in zebrafish embryos using light-activated, negatively charged peptide nucleic acids. J Am Chem Soc 129:11000–11001PubMedCrossRefGoogle Scholar
  55. Tang X, Swaminathan J, Gewirtz AM et al (2008) Regulating gene expression in human leukemia cells using light-activated oligodeoxynucleotides. Nucleic Acids Res 36:559–569PubMedCrossRefGoogle Scholar
  56. Tang XJ, Su M, Yu LL et al (2010) Photomodulating RNA cleavage using photolabile circular antisense oligodeoxynucleotides. Nucleic Acids Res 38:3848–3855PubMedCrossRefGoogle Scholar
  57. Tomasini AJ, Schuler AD, Zebala JA et al (2009) PhotoMorphs: a novel light-activated reagent for controlling gene expression in zebrafish. Genesis 47:736–743PubMedCrossRefGoogle Scholar
  58. Wacheck V, Zangemeister-Wittke U (2006) Antisense molecules for targeted cancer therapy. Crit Rev Oncol Hematol 59:65–73PubMedCrossRefGoogle Scholar
  59. Young DD, Deiters A (2007) Photochemical control of biological processes. Org Biomol Chem 5:999–1005PubMedCrossRefGoogle Scholar
  60. Young DD, Lusic H, Lively MO et al (2008) Gene silencing in mammalian cells with light-activated antisense agents. Chembiochem 9:2937–2940PubMedCrossRefGoogle Scholar
  61. Young D, Lively M, Deiters A (2010) Activation and deactivation of DNAzyme and antisense function with light for the photochemical regulation of gene expression in mammalian cells. J Am Chem Soc 132:6183–6193PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Department of ChemistryNorth Carolina State UniversityRaleighUSA

Personalised recommendations