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Aptazymes: Expanding the Specificity of Natural Catalytic Nucleic Acids by Application of In Vitro Selected Oligonucleotides

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Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 170))

Abstract

Aptazymes are synthetic molecules composed of an aptamer domain and a catalytic active nucleic acid unit, which may be a ribozyme or a DNAzyme. In these constructs the aptamer domain serves as a molecular switch that can regulate the catalytic activity of the ribozyme or DNAzyme subunit. This regulation is triggered by binding of the aptamers target molecule, which causes significant structural changes in the aptamer and thus in the entire aptazyme. Therefore, aptazymes function similar to allosteric enzymes, whose catalytic activity is regulated by binding of ligands (effectors) to allosteric sites due to alteration of the three-dimensional structure of the active site of the enzyme. In case of aptazymes, the allosteric site is composed of an aptamer. Aptazymes can be designed for different applications and have already been used in analytical assays as well as for the regulation of gene expression.

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Abbreviations

ABTS:

2,2′-Azino bis(3-ethylbenzthiazoline)-6 sulfonic acid

ALONA:

Aptazyme-linked oligonucleotide assay

ATP:

Adenosine triphosphate

cOligo:

Complementary oligonucleotide

DNAzyme:

Deoxyribozymes

FRET:

Fluorescence resonance energy transfer

GMP:

Guanosine monophosphate

HDV:

Hepatitis delta virus ribozyme

HHR:

Hammerhead ribozyme

IgE:

Immunoglobulin E

LOD:

Limit of detection

SELEX:

Systematic evolution of ligands by exponential enrichment

VEGF:

Vascular endothelial growth factor

References

  1. Robertson MP, Ellington AD (1999) In vitro selection of an allosteric ribozyme that transduces analytes to amplicons. Nat Biotechnol 17(1):62–66

    Article  CAS  Google Scholar 

  2. Walter J et al (2012) Aptasensors for small molecule detection. Z Naturforsch 67(b):976–986

    Article  CAS  Google Scholar 

  3. Tang J, Breaker RR (1997) Rational design of allosteric ribozymes. Chem Biol 4(6):453–459

    Article  CAS  Google Scholar 

  4. Silverman SK (2003) Rube Goldberg goes (ribo)nuclear? Molecular switches and sensors made from RNA. RNA 9(4):377–383

    Article  CAS  Google Scholar 

  5. Sano M, Kato Y, Taira K (2005) Functional gene-discovery systems based on libraries of hammerhead and hairpin ribozymes and short hairpin RNAs. Mol BioSyst 1(1):27–35

    Article  CAS  Google Scholar 

  6. Felletti M, Hartig JS (2017) Ligand-dependent ribozymes. Wiley Interdiscip Rev RNA 8(2)

    Google Scholar 

  7. Lee ER et al (2010) An allosteric self-splicing ribozyme triggered by a bacterial second messenger. Science 329(5993):845–848

    Article  CAS  Google Scholar 

  8. Tang J, Breaker RR (1998) Mechanism for allosteric inhibition of an ATP-sensitive ribozyme. Nucleic Acids Res 26(18):4214–4221

    Article  CAS  Google Scholar 

  9. Famulok M, Hartig JS, Mayer G (2007) Functional aptamers and aptazymes in biotechnology, diagnostics, and therapy. Chem Rev 107(9):3715–3743

    Article  CAS  Google Scholar 

  10. Soukup GA, Breaker RR (1999) Design of allosteric hammerhead ribozymes activated by ligand-induced structure stabilization. Struct Folding Des 7(7):783–791

    Article  CAS  Google Scholar 

  11. Zhou ZJ et al (2015) A general approach for rational design of fluorescent DNA aptazyme sensors based on target-induced unfolding of DNA hairpins. Anal Chim Acta 889:179–186

    Article  CAS  Google Scholar 

  12. Pollet J, Strych U, Willson RC (2012) A peroxidase-active aptazyme as an isothermally amplifiable label in an aptazyme-linked oligonucleotide assay for low-picomolar IgE detection. Analyst 137(24):5710–5712

    Article  CAS  Google Scholar 

  13. Kong DM et al (2010) Structure-function study of peroxidase-like G-quadruplex-hemin complexes. Analyst 135(2):321–326

    Article  CAS  Google Scholar 

  14. Wu D et al (2016) Colorimetric detection of proteins based on target-induced activation of aptazyme. Anal Chim Acta 942:68–73

    Article  CAS  Google Scholar 

  15. Helm M et al (2005) Allosterically activated Diels-Alder catalysis by a ribozyme. J Am Chem Soc 127(30):10492–10493

    Article  CAS  Google Scholar 

  16. Yang YJ et al (2016) Aptazyme-gold nanoparticle sensor for amplified molecular probing in living cells. Anal Chem 88(11):5981–5987

    Article  CAS  Google Scholar 

  17. Thompson KM et al (2002) Group I aptazymes as genetic regulatory switches. BMC Biotechnol 2(21):12

    Google Scholar 

  18. Wittmann A, Suess B (2011) Selection of tetracycline inducible self-cleaving ribozymes as synthetic devices for gene regulation in yeast. Mol Biosyst 7(8):2419–2427

    Article  CAS  Google Scholar 

  19. Wieland M, Hartig JS (2008) Improved aptazyme design and in vivo screening enable riboswitching in bacteria. Angew Chem Int Ed 47(14):2604–2607

    Article  CAS  Google Scholar 

  20. Tang WX, Hu JH, Liu DR (2017) Aptazyme-embedded guide RNAs enable ligand-responsive genome editing and transcriptional activation. Nat Commun 8:15939

    Article  CAS  Google Scholar 

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Correspondence to Johanna-Gabriela Walter .

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Walter, JG., Stahl, F. (2019). Aptazymes: Expanding the Specificity of Natural Catalytic Nucleic Acids by Application of In Vitro Selected Oligonucleotides. In: Seitz, H., Stahl, F., Walter, JG. (eds) Catalytically Active Nucleic Acids. Advances in Biochemical Engineering/Biotechnology, vol 170. Springer, Cham. https://doi.org/10.1007/10_2019_92

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