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Experimental analysis of the basic idea on the transcription-based diagnostic automata controlled by programmed molecules

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Abstract

Biomolecular computing using the artificial nucleic acid technology is expected to bring new solutions to various health problems. We focus on the noninvasive transcriptome diagnosis by salivary mRNAs and present the novel concept of transcription-based diagnostic automata that are constructed by programmed DNA modules. The main computational element has a stem shaped promoter region and a pseudo-loop shaped read-only memory region for transcription regulation through the conformation change caused by targets. Our system quantifies targets by transcription of malachite green aptamer sequence triggered by the target recognition. This algorithm makes it possible to realize the cost-effective and sequence-specific real-time target detection. Moreover, in the in-vivo therapeutic use, this transcription-based system can release RNA-aptamer drugs multiply at the transcription stage, different from the digestion-based systems by the restriction enzyme which was proposed previously. We verified the sensitivity, the selectivity and the quantitative stability of the diagnostic automata in basic conditions. Our approach will provide promising applications of autonomous intelligent systems using programmed molecules.

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References

  • Babendure JR, Adams SR, Tsien RY (2003) Aptamers switch on fluorescence of triphenylmethane dyes. J Am Chem Soc 125(48):14716–14717

    Article  Google Scholar 

  • Baugh C, Grate D, Wilson C (2000) 2.8 Å crystal structure of the malachite green aptamer. J Mol Biol 301(1):117–128

    Article  Google Scholar 

  • Benenson Y, Paz-Elizur T, Adar R, Keinan E, Livneh Z, Shapiro E (2001) Programmable and autonomous computing machine made of biomolecules. Nature 414:430–434

    Article  Google Scholar 

  • Benenson Y, Gil Ben-Dor U, Adar R, Shapiro E (2004) An autonomous molecular computer for logical control of gene expression. Nature 429:423–429

    Article  Google Scholar 

  • Braich RS, Chelyapov N, Johnson C, Rothemund PWK, Adleman L (2002) Solution of a 20-variable 3-SAT problem on a DNA computer. Science 296:499–502

    Article  Google Scholar 

  • Bunka DHJ, Stockley PG (2006) Aptamers come of age—at last. Nat Rev Microbiol 4:588–596

    Article  Google Scholar 

  • De Silva AP, McClenaghan ND (2004) Molecular-scale logic gates. Chemistry 10:574–586

    Article  Google Scholar 

  • Famulok M (2004) Chemical biology: green fluorescent RNA. Nature 430(7003):976–977

    Article  Google Scholar 

  • Ginzinger DG (2002) Gene quantification using real-time quantitative PCR: an emerging technology hits the mainstream. Exp Hematol 30:503–512

    Article  Google Scholar 

  • Grate D, Wilson C (1999) Laser-mediated, site-specific inactivation of RNA transcripts. Proc Natl Acad Sci USA 96(11):6131–6136

    Article  Google Scholar 

  • Hirabayashi M, Taira S, Kobayashi S, Konishi K, Katoh K, Hiratsuka Y, Kodaka M, Uyeda TQP, Yumoto N, Kubo T (2006) Malachite green-conjugated microtubules as mobile bioprobes selective for malachite green aptamers with capturing/releasing ability. Biotechnol Bioeng 94(3):473–480

    Article  Google Scholar 

  • Kolpashchikov DM, Stojanovic MN (2005) Boolean control of aptamer binding states. J Am Chem Soc 127:11348–11351

    Article  Google Scholar 

  • Li Y, John MARSt, Zhou X, Kim Y, Sinha U, Jordan RCK, Eisele D, Abemayor E, Elashoff D, Park N-H, Wong DT (2004) Salivary transcriptome diagnostics for oral cancer detection. Clin Cancer Res 10:8442–8450

    Article  Google Scholar 

  • Okamoto A, Tanaka K, Saito I (2004) DNA logic gates. J Am Chem Soc 126:9458–9463

    Article  Google Scholar 

  • Saghatelian A, Voelcker NH, Guckian KM, Lin VS-Y, Ghadiri MR (2003) DNA-based photonic logic gates: AND, NAND, and INHIBIT. J Am Chem Soc 125:346–347

    Article  Google Scholar 

  • Stojanovic MN, Kolpashchikov DM (2004) Modular aptameric sensors. J Am Chem Soc 126(30):9266–9270

    Article  Google Scholar 

  • Wang H, Hall JG, Liu Q, Smith LM (2001) A DNA computing readout operation based on structure-specific cleavage. Nat Biotechnol 19:1053–1059

    Article  Google Scholar 

  • Winfree E, Liu FR, Wenzler LA, Seeman NC (1998) Design and self-assembly of two-dimensional DNA crystals. Nature 394:539–544

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Quantum Engineering and Systems Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan

    Miki Hirabayashi & Hirotada Ohashi

  2. Neuroscience Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan

    Tai Kubo

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  1. Miki Hirabayashi
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  2. Hirotada Ohashi
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  3. Tai Kubo
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Correspondence to Miki Hirabayashi.

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Hirabayashi, M., Ohashi, H. & Kubo, T. Experimental analysis of the basic idea on the transcription-based diagnostic automata controlled by programmed molecules. Nat Comput 7, 403–421 (2008). https://doi.org/10.1007/s11047-008-9069-9

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  • DOI: https://doi.org/10.1007/s11047-008-9069-9

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