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RNA synthetic biology

Abstract

RNA molecules play important and diverse regulatory roles in the cell by virtue of their interaction with other nucleic acids, proteins and small molecules. Inspired by this natural versatility, researchers have engineered RNA molecules with new biological functions. In the last two years efforts in synthetic biology have produced novel, synthetic RNA components capable of regulating gene expression in vivo largely in bacteria and yeast, setting the stage for scalable and programmable cellular behavior. Immediate challenges for this emerging field include determining how computational and directed-evolution techniques can be implemented to increase the complexity of engineered RNA systems, as well as determining how such systems can be broadly extended to mammalian systems. Further challenges include designing RNA molecules to be sensors of intracellular and environmental stimuli, probes to explore the behavior of biological networks and components of engineered cellular control systems.

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Figure 1: Endogenous RNAs that regulate gene expression.
Figure 2: Engineered riboregulators.
Figure 3: Engineered ribosome-mRNA pairs.
Figure 4: Engineered ligand-controlled riboregulators.
Figure 5: Engineered ribozyme-mediated gene expression.
Figure 6: Engineered RNA transcriptional activators.
Figure 7: In vitro nucleic acid systems.

References

  1. Hasty, J., McMillen, D., Isaacs, F. & Collins, J.J. Computational studies of gene regulatory networks: in numero molecular biology. Nat. Rev. Genet. 2, 268–279 (2001).

    CAS  PubMed  Google Scholar 

  2. Hasty, J., McMillen, D. & Collins, J.J. Engineered gene circuits. Nature 420, 224–230 (2002).

    CAS  PubMed  Google Scholar 

  3. Wall, M.E., Hlavacek, W.S. & Savageau, M.A. Design of gene circuits: lessons from bacteria. Nat. Rev. Genet. 5, 34–42 (2004).

    CAS  PubMed  Google Scholar 

  4. Benner, S.A. & Sismour, A.M. Synthetic biology. Nat. Rev. Genet. 6, 533–543 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. McDaniel, R. & Weiss, R. Advances in synthetic biology: on the path from prototypes to applications. Curr. Opin. Biotechnol. 16, 476–483 (2005).

    CAS  PubMed  Google Scholar 

  6. Sprinzak, D. & Elowitz, M.B. Reconstruction of genetic circuits. Nature 438, 443–448 (2005).

    CAS  PubMed  Google Scholar 

  7. Thompson, K.M., Syrett, H.A., Knudsen, S.M. & Ellington, A.D. Group I aptazymes as genetic regulatory switches. BMC Biotechnol. 2, 21 (2002).

    PubMed  PubMed Central  Google Scholar 

  8. Werstuck, G. & Green, M.R. Controlling gene expression in living cells through small molecule-RNA interactions. Science 282, 296–298 (1998).

    Article  CAS  PubMed  Google Scholar 

  9. Grate, D. & Wilson, C. Inducible regulation of the S. cerevisiae cell cycle mediated by an RNA aptamer-ligand complex. Bioorg. Med. Chem. 9, 2565–2570 (2001).

    CAS  PubMed  Google Scholar 

  10. Saha, S., Ansari, A.Z., Jarrell, K.A. & Ptashne, M. RNA sequences that work as transcriptional activating regions. Nucleic Acids Res. 31, 1565–1570 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Buskirk, A.R., Kehayova, P.D., Landrigan, A. & Liu, D.R. In vivo evolution of an RNA-based transcriptional activator. Chem. Biol. 10, 533–540 (2003).

    CAS  PubMed  Google Scholar 

  12. Buskirk, A.R., Landrigan, A. & Liu, D.R. Engineering a ligand-dependent RNA transcriptional activator. Chem. Biol. 11, 1157–1163 (2004).

    CAS  PubMed  Google Scholar 

  13. Isaacs, F.J. et al. Engineered riboregulators enable post-transcriptional control of gene expression. Nat. Biotechnol. 22, 841–847 (2004).

    CAS  PubMed  Google Scholar 

  14. Suess, B., Fink, B., Berens, C., Stentz, R. & Hillen, W. A theophylline responsive riboswitch based on helix slipping controls gene expression in vivo. Nucleic Acids Res. 32, 1610–1614 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Yen, L. et al. Exogenous control of mammalian gene expression through modulation of RNA self-cleavage. Nature 431, 471–476 (2004).

    CAS  PubMed  Google Scholar 

  16. Bayer, T.S. & Smolke, C.D. Programmable ligand-controlled riboregulators of eukaryotic gene expression. Nat. Biotechnol. 23, 337–343 (2005).

    CAS  PubMed  Google Scholar 

  17. Desai, S.K. & Gallivan, J.P. Genetic screens and selections for small molecules based on a synthetic riboswitch that activates protein translation. J. Am. Chem. Soc. 126, 13247–13254 (2004).

    CAS  PubMed  Google Scholar 

  18. Rackham, O. & Chin, J.W. A network of orthogonal ribosome-mRNA pairs. Nat. Chem. Biol. 1, 159–166 (2005).

    CAS  PubMed  Google Scholar 

  19. Rackham, O. & Chin, J.W. Cellular logic with orthogonal ribosomes. J. Am. Chem. Soc. 127, 17584–17585 (2005).

    CAS  PubMed  Google Scholar 

  20. Shine, J. & Dalgarno, L. Identical 3′-terminal octanucleotide sequence in 18S ribosomal ribonucleic acid from different eukaryotes. A proposed role for this sequence in the recognition of terminator codons. Biochem. J. 141, 609–615 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Yusupova, G.Z., Yusupov, M.M., Cate, J.H. & Noller, H.F. The path of messenger RNA through the ribosome. Cell 106, 233–241 (2001).

    CAS  PubMed  Google Scholar 

  22. Wikstrom, P.M., Lind, L.K., Berg, D.E. & Bjork, G.R. Importance of mRNA folding and start codon accessibility in the expression of genes in a ribosomal protein operon of Escherichia coli. J. Mol. Biol. 224, 949–966 (1992).

    CAS  PubMed  Google Scholar 

  23. Lease, R.A. & Belfort, M. A trans-acting RNA as a control switch in Escherichia coli: DsrA modulates function by forming alternative structures. Proc. Natl. Acad. Sci. USA 97, 9919–9924 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Majdalani, N., Vanderpool, C.K. & Gottesman, S. Bacterial small RNA regulators. Crit. Rev. Biochem. Mol. Biol. 40, 93–113 (2005).

    CAS  PubMed  Google Scholar 

  25. Gottesman, S. The small RNA regulators of Escherichia coli: roles and mechanisms. Annu. Rev. Microbiol. 58, 303–328 (2004).

    CAS  PubMed  Google Scholar 

  26. Franch, T., Petersen, M., Wagner, E.G., Jacobsen, J.P. & Gerdes, K. Antisense RNA regulation in prokaryotes: rapid RNA/RNA interaction facilitated by a general U-turn loop structure. J. Mol. Biol. 294, 1115–1125 (1999).

    CAS  PubMed  Google Scholar 

  27. Majdalani, N., Hernandez, D. & Gottesman, S. Regulation and mode of action of the second small RNA activator of RpoS translation, RprA. Mol. Microbiol. 46, 813–826 (2002).

    CAS  PubMed  Google Scholar 

  28. Wagner, E.G. & Flardh, K. Antisense RNAs everywhere? Trends Genet. 18, 223–226 (2002).

    CAS  PubMed  Google Scholar 

  29. Good, L. Translation repression by antisense sequences. Cell. Mol. Life Sci. 60, 854–861 (2003).

    CAS  PubMed  Google Scholar 

  30. Ting, A.Y. et al. Phage-display evolution of tyrosine kinases with altered nucleotide specificity. Biopolymers 60, 220–228 (2001).

    CAS  PubMed  Google Scholar 

  31. Shi, Y. & Koh, J.T. Selective regulation of gene expression by an orthogonal estrogen receptor-ligand pair created by polar-group exchange. Chem. Biol. 8, 501–510 (2001).

    CAS  PubMed  Google Scholar 

  32. Pestova, T.V. et al. Molecular mechanisms of translation initiation in eukaryotes. Proc. Natl. Acad. Sci. USA 98, 7029–7036 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Stoneley, M. & Willis, A.E. Cellular internal ribosome entry segments: structures, trans-acting factors and regulation of gene expression. Oncogene 23, 3200–3207 (2004).

    CAS  PubMed  Google Scholar 

  34. Rasmussen, U.B., Mygind, B. & Nygaard, P. Purification and some properties of uracil phosphoribosyltransferase from Escherichia coli K12. Biochim. Biophys. Acta 881, 268–275 (1986).

    CAS  PubMed  Google Scholar 

  35. Winkler, W.C. & Breaker, R.R. Regulation of Bacterial Gene Expression by Riboswitches. Annu. Rev. Microbiol. 59, 487–517 (2005).

    CAS  PubMed  Google Scholar 

  36. Hermann, T. & Patel, D.J. Adaptive recognition by nucleic acid aptamers. Science 287, 820–825 (2000).

    CAS  PubMed  Google Scholar 

  37. Winkler, W., Nahvi, A. & Breaker, R.R. Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature 419, 952–956 (2002).

    CAS  PubMed  Google Scholar 

  38. Winkler, W.C., Nahvi, A., Roth, A., Collins, J.A. & Breaker, R.R. Control of gene expression by a natural metabolite-responsive ribozyme. Nature 428, 281–286 (2004).

    CAS  PubMed  Google Scholar 

  39. Rojas, A.A. et al. Hammerhead-mediated processing of satellite pDo500 family transcripts from Dolichopoda cave crickets. Nucleic Acids Res. 28, 4037–4043 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Ferbeyre, G., Smith, J.M. & Cedergren, R. Schistosome satellite DNA encodes active hammerhead ribozymes. Mol. Cell. Biol. 18, 3880–3888 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Morcos, P.A. Achieving efficient delivery of morpholino oligos in cultured cells. Genesis 30, 94–102 (2001).

    CAS  PubMed  Google Scholar 

  42. Aszalos, A., Lemanski, P., Robison, R., Davis, S. & Berk, B. Identification of antibiotic 1037 as toyocamycin. J. Antibiot. (Tokyo) 19, 285 (1966).

    CAS  Google Scholar 

  43. Gardner, T.S., Cantor, C.R. & Collins, J.J. Construction of a genetic toggle switch in Escherichia coli. Nature 403, 339–342 (2000).

    CAS  PubMed  Google Scholar 

  44. Becskei, A., Seraphin, B. & Serrano, L. Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion. EMBO J. 20, 2528–2535 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Isaacs, F.J., Hasty, J., Cantor, C.R. & Collins, J.J. Prediction and measurement of an autoregulatory genetic module. Proc. Natl. Acad. Sci. USA 100, 7714–7719 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Kobayashi, H. et al. Programmable cells: interfacing natural and engineered gene networks. Proc. Natl. Acad. Sci. USA 101, 8414–8419 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Kramer, B.P. et al. An engineered epigenetic transgene switch in mammalian cells. Nat. Biotechnol. 22, 867–870 (2004).

    CAS  PubMed  Google Scholar 

  48. Ptashne, M. & Gann, A. Transcriptional activation by recruitment. Nature 386, 569–577 (1997).

    CAS  PubMed  Google Scholar 

  49. Sengupta, D.J., Wickens, M. & Fields, S. Identification of RNAs that bind to a specific protein using the yeast three-hybrid system. RNA 5, 596–601 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Bernstein, D.S., Buter, N., Stumpf, C. & Wickens, M. Analyzing mRNA-protein complexes using a yeast three-hybrid system. Methods 26, 123–141 (2002).

    CAS  PubMed  Google Scholar 

  51. Witherell, G.W., Gott, J.M. & Uhlenbeck, O.C. Specific interaction between RNA phage coat proteins and RNA. Prog. Nucleic Acid Res. Mol. Biol. 40, 185–220 (1991).

    CAS  PubMed  Google Scholar 

  52. Stockley, P.G. et al. Probing sequence-specific RNA recognition by the bacteriophage MS2 coat protein. Nucleic Acids Res. 23, 2512–2518 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Sando, S., Narita, A., Abe, K. & Aoyama, Y. Doubly catalytic sensing of HIV-1-related CCR5 sequence in prokaryotic cell-free translation system using riboregulator-controlled luciferase activity. J. Am. Chem. Soc. 127, 5300–5301 (2005).

    CAS  PubMed  Google Scholar 

  55. Penchovsky, R. & Breaker, R.R. Computational design and experimental validation of oligonucleotide-sensing allosteric ribozymes. Nat. Biotechnol. 23, 1424–1433 (2005).

    CAS  PubMed  Google Scholar 

  56. Yokobayashi, Y., Weiss, R. & Arnold, F.H. Directed evolution of a genetic circuit. Proc. Natl. Acad. Sci. USA 99, 16587–16591 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Tian, J. et al. Accurate multiplex gene synthesis from programmable DNA microchips. Nature 432, 1050–1054 (2004).

    CAS  PubMed  Google Scholar 

  58. Porteus, M.H. & Carroll, D. Gene targeting using zinc finger nucleases. Nat. Biotechnol. 23, 967–973 (2005).

    CAS  PubMed  Google Scholar 

  59. Smith, H.O., Hutchison, C.A., III, Pfannkoch, C. & Venter, J.C. Generating a synthetic genome by whole genome assembly: phiX174 bacteriophage from synthetic oligonucleotides. Proc. Natl. Acad. Sci. USA 100, 15440–15445 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Chan, L.Y., Kosuri, S. & Endy, D. Refactoring bacteriophage T7. Mol. Syst. Biol., Published online 13 September 2005 (doi:10.1038/msb4100025).

  61. Looger, L.L., Dwyer, M.A., Smith, J.J. & Hellinga, H.W. Computational design of receptor and sensor proteins with novel functions. Nature 423, 185–190 (2003).

    CAS  PubMed  Google Scholar 

  62. Dueber, J.E., Yeh, B.J., Chak, K. & Lim, W.A. Reprogramming control of an allosteric signaling switch through modular recombination. Science 301, 1904–1908 (2003).

    CAS  PubMed  Google Scholar 

  63. Martin, V.J., Pitera, D.J., Withers, S.T., Newman, J.D. & Keasling, J.D. Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nat. Biotechnol. 21, 796–802 (2003).

    CAS  PubMed  Google Scholar 

  64. Rabaey, K. & Verstraete, W. Microbial fuel cells: novel biotechnology for energy generation. Trends Biotechnol. 23, 291–298 (2005).

    CAS  PubMed  Google Scholar 

  65. Endy, D. Foundations for engineering biology. Nature 438, 449–453 (2005).

    CAS  PubMed  Google Scholar 

  66. Eddy, S.R. Non-coding RNA genes and the modern RNA world. Nat. Rev. Genet. 2, 919–929 (2001).

    CAS  PubMed  Google Scholar 

  67. Kruger, K. et al. Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell 31, 147–157 (1982).

    CAS  PubMed  Google Scholar 

  68. Guerrier-Takada, C., Gardiner, K., Marsh, T., Pace, N. & Altman, S. The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35, 849–857 (1983).

    CAS  PubMed  Google Scholar 

  69. Doudna, J.A. & Cech, T.R. The chemical repertoire of natural ribozymes. Nature 418, 222–228 (2002).

    CAS  PubMed  Google Scholar 

  70. Wagner, E.G. & Simons, R.W. Antisense RNA control in bacteria, phages, and plasmids. Annu. Rev. Microbiol. 48, 713–742 (1994).

    CAS  PubMed  Google Scholar 

  71. Masse, E., Escorcia, F.E. & Gottesman, S. Coupled degradation of a small regulatory RNA and its mRNA targets in Escherichia coli. Genes Dev. 17, 2374–2383 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Nissen, P., Hansen, J., Ban, N., Moore, P.B. & Steitz, T.A. The structural basis of ribosome activity in peptide bond synthesis. Science 289, 920–930 (2000).

    CAS  PubMed  Google Scholar 

  73. Steitz, T.A. & Moore, P.B. RNA, the first macromolecular catalyst: the ribosome is a ribozyme. Trends Biochem. Sci. 28, 411–418 (2003).

    CAS  PubMed  Google Scholar 

  74. Weinger, J.S., Parnell, K.M., Dorner, S., Green, R. & Strobel, S.A. Substrate-assisted catalysis of peptide bond formation by the ribosome. Nat. Struct. Mol. Biol. 11, 1101–1106 (2004).

    CAS  PubMed  Google Scholar 

  75. Nahas, M.K. et al. Observation of internal cleavage and ligation reactions of a ribozyme. Nat. Struct. Mol. Biol. 11, 1107–1113 (2004).

    CAS  PubMed  Google Scholar 

  76. Hampel, A. & Cowan, J.A. A unique mechanism for RNA catalysis: the role of metal cofactors in hairpin ribozyme cleavage. Chem. Biol. 4, 513–517 (1997).

    CAS  PubMed  Google Scholar 

  77. Narlikar, G.J. & Herschlag, D. Mechanistic aspects of enzymatic catalysis: lessons from comparison of RNA and protein enzymes. Annu. Rev. Biochem. 66, 19–59 (1997).

    CAS  PubMed  Google Scholar 

  78. Winkler, W.C., Cohen-Chalamish, S. & Breaker, R.R. An mRNA structure that controls gene expression by binding FMN. Proc. Natl. Acad. Sci. USA 99, 15908–15913 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Fire, A. et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806–811 (1998).

    CAS  PubMed  Google Scholar 

  80. Novina, C.D. & Sharp, P.A. The RNAi revolution. Nature 430, 161–164 (2004).

    CAS  PubMed  Google Scholar 

  81. Zamore, P.D. & Haley, B. Ribo-gnome: the big world of small RNAs. Science 309, 1519–1524 (2005).

    CAS  PubMed  Google Scholar 

  82. Lau, N.C., Lim, L.P., Weinstein, E.G. & Bartel, D.P. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294, 858–862 (2001).

    CAS  PubMed  Google Scholar 

  83. Lee, R.C. & Ambros, V. An extensive class of small RNAs in Caenorhabditis elegans. Science 294, 862–864 (2001).

    CAS  PubMed  Google Scholar 

  84. Lagos-Quintana, M., Rauhut, R., Lendeckel, W. & Tuschl, T. Identification of novel genes coding for small expressed RNAs. Science 294, 853–858 (2001).

    CAS  PubMed  Google Scholar 

  85. Rhoades, M.W. et al. Prediction of plant microRNA targets. Cell 110, 513–520 (2002).

    CAS  PubMed  Google Scholar 

  86. Yekta, S., Shih, I.H. & Bartel, D.P. MicroRNA-directed cleavage of HOXB8 mRNA. Science 304, 594–596 (2004).

    CAS  PubMed  Google Scholar 

  87. Ellington, A.D. & Szostak, J.W. In vitro selection of RNA molecules that bind specific ligands. Nature 346, 818–822 (1990).

    CAS  PubMed  Google Scholar 

  88. Tuerk, C. & Gold, L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249, 505–510 (1990).

    CAS  PubMed  Google Scholar 

  89. Ellington, A.D. & Szostak, J.W. Selection in vitro of single-stranded DNA molecules that fold into specific ligand-binding structures. Nature 355, 850–852 (1992).

    CAS  PubMed  Google Scholar 

  90. Breaker, R.R. In Vitro Selection of Catalytic Polynucleotides. Chem. Rev. 97, 371–390 (1997).

    CAS  PubMed  Google Scholar 

  91. Tang, J. & Breaker, R.R. Rational design of allosteric ribozymes. Chem. Biol. 4, 453–459 (1997).

    CAS  PubMed  Google Scholar 

  92. Unrau, P.J. & Bartel, D.P. RNA-catalysed nucleotide synthesis. Nature 395, 260–263 (1998).

    CAS  PubMed  Google Scholar 

  93. Araki, M., Okuno, Y., Hara, Y. & Sugiura, Y. Allosteric regulation of a ribozyme activity through ligand-induced conformational change. Nucleic Acids Res. 26, 3379–3384 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Robertson, M.P. & Ellington, A.D. In vitro selection of an allosteric ribozyme that transduces analytes to amplicons. Nat. Biotechnol. 17, 62–66 (1999).

    CAS  PubMed  Google Scholar 

  95. Soukup, G.A. & Breaker, R.R. Engineering precision RNA molecular switches. Proc. Natl. Acad. Sci. USA 96, 3584–3589 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Tang, J. & Breaker, R.R. Structural diversity of self-cleaving ribozymes. Proc. Natl. Acad. Sci. USA 97, 5784–5789 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Jose, A.M., Soukup, G.A. & Breaker, R.R. Cooperative binding of effectors by an allosteric ribozyme. Nucleic Acids Res. 29, 1631–1637 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Breaker, R.R. & Joyce, G.F.A. DNA enzyme that cleaves RNA. Chem. Biol. 1, 223–229 (1994).

    CAS  PubMed  Google Scholar 

  99. Breaker, R.R. DNA enzymes. Nat. Biotechnol. 15, 427–431 (1997).

    CAS  PubMed  Google Scholar 

  100. Silverman, S.K. In vitro selection, characterization, and application of deoxyribozymes that cleave RNA. Nucleic Acids Res. 33, 6151–6163 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Ruben, A.J. & Landweber, L.F. The past, present and future of molecular computing. Nat. Rev. Mol. Cell Biol. 1, 69–72 (2000).

    CAS  PubMed  Google Scholar 

  102. Seeman, N.C. DNA in a material world. Nature 421, 427–431 (2003).

    PubMed  Google Scholar 

  103. Tang, J. & Breaker, R.R. Examination of the catalytic fitness of the hammerhead ribozyme by in vitro selection. RNA 3, 914–925 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Tang, J. & Breaker, R.R. Mechanism for allosteric inhibition of an ATP-sensitive ribozyme. Nucleic Acids Res. 26, 4214–4221 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Stojanovic, M.N. & Stefanovic, D. A deoxyribozyme-based molecular automaton. Nat. Biotechnol. 21, 1069–1074 (2003).

    CAS  PubMed  Google Scholar 

  106. Benenson, Y. et al. Programmable and autonomous computing machine made of biomolecules. Nature 414, 430–434 (2001).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  108. Samarsky, D.A. et al. A small nucleolar RNA:ribozyme hybrid cleaves a nucleolar RNA target in vivo with near-perfect efficiency. Proc. Natl. Acad. Sci. USA 96, 6609–6614 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Jason Chin for providing access to unpublished results in the form of a preprint manuscript and George Church for insightful and relevant discussions. We also thank Nick Reppas, Duhee Bang and the anonymous reviewers for providing valuable suggestions to improve the paper. This work was supported by the National Institutes of Health and the National Science Foundation.

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Isaacs, F., Dwyer, D. & Collins, J. RNA synthetic biology. Nat Biotechnol 24, 545–554 (2006). https://doi.org/10.1038/nbt1208

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