Skip to main content
SpringerLink
Log in
Book cover

From Nucleic Acids Sequences to Molecular Medicine pp 275–291Cite as

Activation and Deactivation of Antisense and RNA Interference Function with Light

  • Chapter
  • First Online:

Part of the book series: RNA Technologies ((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.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Abdelgany A, Wood M, Beeson D (2007) Hairpin DNAzymes: a new tool for efficient cellular gene silencing. J Gene Med 9:727–738

    Article  PubMed  CAS  Google Scholar 

  • Aboul-Fadl T (2005) Antisense oligonucleotides: the state of the art. Curr Med Chem 12:2193–2214

    Article  PubMed  CAS  Google Scholar 

  • Adams SR, Tsien RY (1993) Controlling cell chemistry with caged compounds. Annu Rev Physiol 55:755–784

    Article  PubMed  CAS  Google Scholar 

  • Ando H, Furuta T, Tsien RY et al (2001) Photo-mediated gene activation using caged RNA/DNA in zebrafish embryos. Nat Genet 28:317–325

    Article  PubMed  CAS  Google Scholar 

  • Aravin A, Tuschl T (2005) Identification and characterization of small RNAs involved in RNA silencing. FEBS Lett 579:5830–5840

    Article  PubMed  CAS  Google Scholar 

  • 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 68:8361–8367

    Article  PubMed  CAS  Google Scholar 

  • 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 4:431–440

    Article  PubMed  CAS  Google Scholar 

  • Bolcato-Bellemin AL, Bonnet ME, Creusat G et al (2007) Sticky overhangs enhance siRNA-mediated gene silencing. Proc Natl Acad Sci USA 104:16050–16065

    Article  PubMed  CAS  Google Scholar 

  • 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 365:90–108

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Dudgeon N, Shen L et al (2005) Chemical modification of gene silencing oligonucleotides for drug discovery and development. Drug Discov Today 10:587–593

    Article  PubMed  Google Scholar 

  • 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 317:797–805

    Article  PubMed  CAS  Google Scholar 

  • Chiu YL, Rana TM (2003) SiRNA function in RNAi: a chemical modification analysis. RNA 9:1034–1048

    Article  PubMed  CAS  Google Scholar 

  • Dean NM, Bennett CF (2003) Antisense oligonucleotide-based therapeutics for cancer. Oncogene 22:9087–9096

    Article  PubMed  CAS  Google Scholar 

  • Deiters A (2009) Light activation as a method of regulating and studying gene expression. Curr Opin Chem Biol 13:678–686

    Article  PubMed  CAS  Google Scholar 

  • Deiters A (2010) Principles and applications of the photochemical control of cellular processes. Chembiochem 11:47–53

    Article  PubMed  CAS  Google Scholar 

  • 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 132:15644–15650

    Article  PubMed  CAS  Google Scholar 

  • Dmochowski IJ, Tang XJ (2007) Taking control of gene expression with light-activated oligonucleotides. Biotechniques 43:161–171

    Article  PubMed  CAS  Google Scholar 

  • Elbashir S, Harborth J, Lendeckel W et al (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494–498

    Article  PubMed  CAS  Google Scholar 

  • Ellis-Davies GC (2007) Caged compounds: photorelease technology for control of cellular chemistry and physiology. Nat Methods 4:619–628

    Article  PubMed  CAS  Google Scholar 

  • Forman J, Dietrich M, Monroe WT (2007) Photobiological and thermal effects of photoactivating UVA light doses on cell cultures. Photochem Photobiol Sci 6:649–658

    Article  PubMed  CAS  Google Scholar 

  • Han G, Mokari T, Ajo-Franklin C et al (2008) Caged quantum dots. J Am Chem Soc 130:15811–15813

    Article  PubMed  CAS  Google Scholar 

  • 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 13:83–105

    Article  PubMed  CAS  Google Scholar 

  • Heasman J (2002) Morpholino oligos: making sense of antisense? Dev Biol 243:209–214

    Article  PubMed  CAS  Google Scholar 

  • Höbartner C, Silverman SK (2005) Modulation of RNA tertiary folding by incorporation of caged nucleotides. Angew Chem Int Ed 44:7305–7309

    Article  Google Scholar 

  • Ito H, Liang X, Nishioka H et al (2010) Construction of photoresponsive RNA for photoswitching RNA hybridization. Org Biomol Chem 8:5519–5524

    Article  PubMed  CAS  Google Scholar 

  • Jain PK, Shah S, Friedman SH (2010) Patterning of gene expression using new photolabile groups applied to light activated RNAi. J Am Chem Soc 133:440–446

    Article  PubMed  Google Scholar 

  • 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 7:196–206

    Article  PubMed  CAS  Google Scholar 

  • Karkare S, Bhatnagar D (2006) Promising nucleic acid analogs and mimics: characteristic features and applications of PNA, LNA, and morpholino. Appl Microbiol Biotechnol 71:575–586

    Article  PubMed  CAS  Google Scholar 

  • Kim SH, Jeong JH, Lee SH et al (2006) PEG conjugated VEGF siRNA for anti-angiogenic gene therapy. J Control Release 116:123–129

    Article  PubMed  CAS  Google Scholar 

  • Kumar A, Yellepeddi VK, Davies GE et al (2010) Enhanced gene transfection efficiency by polyamidoamine (PAMAM) dendrimers modified with ornithine residues. Int J Pharm 392:294–303

    Article  PubMed  CAS  Google Scholar 

  • 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 1790:1170–1178

    Article  PubMed  CAS  Google Scholar 

  • Layzer JM, McCaffrey AP, Tanner AK et al (2004) In vivo activity of nuclease-resistant siRNAs. RNA 10:766–771

    Article  PubMed  CAS  Google Scholar 

  • 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 4:409–427

    Article  PubMed  CAS  Google Scholar 

  • Matsunaga D, Asanuma H, Komiyama M (2004) Photoregulation of RNA digestion by RNase H with azobenzene-tethered DNA. J Am Chem Soc 126:11452–11453

    Article  PubMed  CAS  Google Scholar 

  • Mayer G, Heckel A (2006) Biologically active molecules with a "light switch". Angew Chem Int Ed 45:4900–4921

    Article  CAS  Google Scholar 

  • Meister G, Tuschl T (2004) Mechanisms of gene silencing by double-stranded RNA. Nature 431:343–349

    Article  PubMed  CAS  Google Scholar 

  • Meng XM, Chen XY, Fu Y et al (2008) Photolysis of caged compounds and its applications to chemical biology. Prog Chem 20:2034–2044

    CAS  Google Scholar 

  • Mikat V, Heckel A (2007) Light-dependent RNA interference with nucleobase-caged siRNAs. RNA 13:2341–2347

    Article  PubMed  CAS  Google Scholar 

  • Moulton HM, Moulton JD (2010) Morpholinos and their peptide conjugates: therapeutic promise and challenge for Duchenne muscular dystrophy. Biochim Biophys Acta 1798:2296–2303

    Article  PubMed  CAS  Google Scholar 

  • Nguyen QN, Chavli RV, Marques JT et al (2006) Light controllable siRNAs regulate gene suppression and phenotypes in cells. Biochim Biophys Acta 1758:394–403

    Article  PubMed  CAS  Google Scholar 

  • Nielsen PE, Egholm M, Berg RH et al (1991) Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science 254:1497–1500

    Article  PubMed  CAS  Google Scholar 

  • Ouyang X, Shestopalov IA, Sinha S et al (2009) Versatile synthesis and rational design of caged morpholinos. J Am Chem Soc 131:13255–13269

    Article  PubMed  CAS  Google Scholar 

  • Palma E, Cho MJ (2007) Improved systemic pharmacokinetics, biodistribution, and antitumor activity of CpG oligodeoxynucleotides complexed to endogenous antibodies in vivo. J Control Release 120:95–103

    Article  PubMed  CAS  Google Scholar 

  • Priestman MA, Lawrence DS (2010) Light-mediated remote control of signaling pathways. Biochim Biophys Acta 1804:547–558

    Article  PubMed  CAS  Google Scholar 

  • Richards JL, Tang X, Turetsky A et al (2008) RNA bandages for photoregulating in vitro protein synthesis. Bioorg Med Chem Lett 18:6255–6258

    Article  PubMed  CAS  Google Scholar 

  • Richards JL, Seward GK, Wang YH et al (2010) Turning the 10–23 DNAzyme on and off with light. Chembiochem 11:320–324

    Article  PubMed  CAS  Google Scholar 

  • Riggsbee CW, Deiters A (2010) Recent advances in the photochemical control of protein function. Trends Biotechnol 28:468–475

    Article  PubMed  CAS  Google Scholar 

  • Shah S, Friedman SH (2007) Tolerance of RNA interference toward modifications of the 5′ antisense phosphate of small interfering RNA. Oligonucleotides 17:35–43

    Article  PubMed  CAS  Google Scholar 

  • Shah S, Rangarajan S, Friedman SH (2005) Light activated RNA interference. Angew Chem Int Ed 44:1328–1332

    Article  CAS  Google Scholar 

  • 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 37:4508–4517

    Article  PubMed  CAS  Google Scholar 

  • Shestopalov IA, Sinha S, Chen JK (2007) Light-controlled gene silencing in zebrafish embryos. Nat Chem Biol 3:650–651

    Article  PubMed  CAS  Google Scholar 

  • Schulte-Merker S, Lee KJ, McMahon AP et al (1997) The zebrafish organizer requires Chordin. Nature 387:862–863

    Article  PubMed  CAS  Google Scholar 

  • 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 7:651–660

    Article  PubMed  CAS  Google Scholar 

  • 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 129:11000–11001

    Article  PubMed  CAS  Google Scholar 

  • Tang X, Swaminathan J, Gewirtz AM et al (2008) Regulating gene expression in human leukemia cells using light-activated oligodeoxynucleotides. Nucleic Acids Res 36:559–569

    Article  PubMed  CAS  Google Scholar 

  • Tang XJ, Su M, Yu LL et al (2010) Photomodulating RNA cleavage using photolabile circular antisense oligodeoxynucleotides. Nucleic Acids Res 38:3848–3855

    Article  PubMed  CAS  Google Scholar 

  • Tomasini AJ, Schuler AD, Zebala JA et al (2009) PhotoMorphs: a novel light-activated reagent for controlling gene expression in zebrafish. Genesis 47:736–743

    Article  PubMed  CAS  Google Scholar 

  • Wacheck V, Zangemeister-Wittke U (2006) Antisense molecules for targeted cancer therapy. Crit Rev Oncol Hematol 59:65–73

    Article  PubMed  CAS  Google Scholar 

  • Young DD, Deiters A (2007) Photochemical control of biological processes. Org Biomol Chem 5:999–1005

    Article  PubMed  CAS  Google Scholar 

  • Young DD, Lusic H, Lively MO et al (2008) Gene silencing in mammalian cells with light-activated antisense agents. Chembiochem 9:2937–2940

    Article  PubMed  CAS  Google Scholar 

  • 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 132:6183–6193

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, North Carolina State University, Raleigh, NC, 27695, USA

    Jeane M. Govan & Alexander Deiters

Authors
  1. Jeane M. Govan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexander Deiters
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexander Deiters .

Editor information

Editors and Affiliations

  1. Institute of Chemistry/Biochemistry, Free University Berlin, Thielallee 63, Berlin, 14195, Berlin, Germany

    Volker A. Erdmann

  2. Inst. Bioorganic Chemistry, PAN Poznan, ul. Z. Noskowskiego 12/14, Poznan, 61-704, Poland

    Jan Barciszewski

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Govan, J.M., Deiters, A. (2012). Activation and Deactivation of Antisense and RNA Interference Function with Light. In: Erdmann, V., Barciszewski, J. (eds) From Nucleic Acids Sequences to Molecular Medicine. RNA Technologies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27426-8_11

Download citation

Publish with us

Policies and ethics

Search

Navigation