Foundations for the design and implementation of synthetic genetic circuits

Nature Reviews Genetics

Volumn 13, Issue 6, 2012, Pages 406-420

  Slusarczyk, Adrian L ^a   Lin, Allen ^a   Weiss, Ron ^a,b  

^a USA   (United States)

^b Department of Electrical Engineering and Computer Science   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL SURFACE RECEPTOR; G PROTEIN COUPLED RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE; MOLECULAR SCAFFOLD; RNA; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR NFAT; ZINC FINGER NUCLEASE;

BINDING SITE; CELL COMMUNICATION; CELL CULTURE; CELL CYCLE; CELL DIFFERENTIATION; CELL MIGRATION; DECOMPOSITION; DNA BINDING; EUKARYOTIC CELL; GENE EXPRESSION; GENETIC ENGINEERING; LOSS OF FUNCTION MUTATION; MAMMAL CELL; MOLECULAR INTERACTION; MOLECULAR LIBRARY; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROCESS DESIGN; PROTEIN FOLDING; PROTEIN PROTEIN INTERACTION; PROTEIN SECONDARY STRUCTURE; PROTEIN SYNTHESIS; REGULATORY DNA SEQUENCE; REVIEW; RNA SYNTHESIS; SIGNAL PROCESSING; SIGNAL TRANSDUCTION; SYNTHETIC BIOLOGY; TRANSCRIPTION REGULATION;

ANIMALS; COMPUTER SIMULATION; COMPUTER-AIDED DESIGN; GENE REGULATORY NETWORKS; GENES, SYNTHETIC; GENETIC ENGINEERING; HUMANS; MODELS, GENETIC; SIGNAL TRANSDUCTION;

EID: 84862081641     PISSN: 14710056     EISSN: 14710064     Source Type: Journal    
DOI: 10.1038/nrg3227     Document Type: Review

References (147)

1. Gardner, T. S., Cantor, C. R. & Collins, J. J. Construction of a genetic toggle switch in Escherichia coli. Nature 403, 339-342 (2000). (Pubitemid 30062394)
2. Weiss, R. & Basu, S. The device physics of cellular logic gates. in NSC-1: The First Workshop on Non-Silicon Computing 54-61 (2002).
3. Elowitz, M. B. & Leibler, S. A synthetic oscillatory network of transcriptional regulators. Nature 403, 335-338 (2000). (Pubitemid 30062393)
4. Mukherji, S. & van Oudenaarden, A. Synthetic biology: understanding biological design from synthetic circuits. Nature Rev. Genet. 10, 859-871 (2009).
5. Nandagopal, N. & Elowitz, M. B. Synthetic biology: integrated gene circuits. Science 333, 1244-1248 (2011).
6. Ruder, W. C., Lu, T. & Collins, J. J. Synthetic biology moving into the clinic. Science 333, 1248-1252 (2011).
7. Khalil, A. S. & Collins, J. J. Synthetic biology: applications come of age. Nature Rev. Genet. 11, 367-379 (2010).
8. Yizhar, O. et al. Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477, 171-178 (2011).
9. Carr, P. A. & Church, G. M. Genome engineering. Nature Biotech. 27, 1151-1162 (2009).
10. Ellis, T., Adie, T. & Baldwin, G. S. DNA assembly for synthetic biology: from parts to pathways and beyond. Integr. Biol. 3, 109-118 (2011).
11. Ro, D.-K. et al. Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440, 940-943 (2006).
12. Wang, H. H. et al. Programming cells by multiplex genome engineering and accelerated evolution. Nature 460, 894-898 (2009).
13. Weber, W. et al. A synthetic mammalian gene circuit reveals antituberculosis compounds. Proc. Natl Acad. Sci. USA 105, 9994-9998 (2008).
14. Purnick, P. E. M. & Weiss, R. The second wave of synthetic biology: from modules to systems. Nature Rev. Mol. Cell Biol. 10, 410-422 (2009).
15. Todd, M. H. Computer-aided organic synthesis. Chem. Soc. Rev. 34, 247-266 (2005). (Pubitemid 40444406)
16. MacDonald, J. T., Barnes, C., Kitney, R. I., Freemont, P. S. & Stan, G.-B. V. Computational design approaches and tools for synthetic biology. Integr. Biol. 3, 97-108 (2011).
17. Chandran, D., Bergmann, F. T., Sauro, H. M. & Densmore, D. Design and Analysis of Biomolecular Circuits: Engineering Approaches to Systems and Synthetic Biology 203-224 (Springer, 2011).
18. Beal, J., Lu, T. & Weiss, R. Automatic compilation from high-level biologically-oriented programming language to genetic regulatory networks. PLoS ONE 6, e22490 (2011).
19. Grünberg, R. & Serrano, L. Strategies for protein synthetic biology. Nucleic Acids Res. 38, 2663-2675 (2010).
20. Martin, A. R. C. et al. Protein folds and functions. Structure 6, 875-884 (1998).
21. Lutz, R. & Bujard, H. Independent and tight regulation of transcriptional units in Escherichia coli via the LacR/O, the TetR/O and AraC/I1-I2 regulatory elements. Nucleic Acids Res. 25, 1203-1210 (1997). (Pubitemid 27303212)
22. Choo, Y., Sánchez-García, I. & Klug, A. In vivo repression by a site-specific DNA-binding protein designed against an oncogenic sequence. Nature 372, 642-645 (1994).
23. Klug, A. The discovery of zinc fingers and their applications in gene regulation and genome manipulation. Annu. Rev. Biochem. 79, 213-231 (2010).
24. Boch, J. et al. Breaking the code of DNA binding specificity of TAL-type III effectors. Science 326, 1509-1512 (2009).
25. Moscou, M. J. & Bogdanove, A. J. A simple cipher governs DNA recognition by TAL effectors. Science 326, 1501 (2009).
26. Voytas, D. F. & Joung, J. K. D. N. A. Binding made easy. Science 326, 1491-1492 (2009).
27. Morbitzer, R., Römer, P., Boch, J. & Lahaye, T. Regulation of selected genome loci using de novo-engineered transcription activator-like effector (TALE)-type transcription factors. Proc. Natl Acad. Sci. USA 107, 1-6 (2010).
28. Davidson, E. A. & Ellington, A. D. Synthetic RNA circuits. Nature Chem. Biol. 3, 23-28 (2007). (Pubitemid 46005694)
29. Isaacs, F. J., Dwyer, D. J. & Collins, J. J. RNA synthetic biology. Nature Biotech. 24, 545-554 (2006).
30. Salis, H. M. Mirsky, E. A. & Voigt, C. A. Automated design of synthetic ribosome binding sites to control protein expression. Nature Biotech. 27, 946-950 (2009).
31. Yokobayashi, Y., Weiss, R. & Arnold, F. H. Directed evolution of a genetic circuit. Proc. Natl Acad. Sci. USA 99, 16587-16591 (2002). (Pubitemid 36034016)
32. Deans, T. L., Cantor, C. R. & Collins, J. J. A tunable genetic switch based on RNAi and repressor proteins for regulating gene expression in mammalian cells. Cell 130, 363-372 (2007). (Pubitemid 47081136)
33. Rinaudo, K. et al. A universal RNAi-based logic evaluator that operates in mammalian cells. Nature Biotech. 25, 795-801 (2007). (Pubitemid 47052185)
34. Xie, Z., Liu, S. J., Bleris, L. & Benenson, Y. Logic integration of mRNA signals by an RNAi-based molecular computer. Nucleic Acids Res. 38, 2692-2701 (2010).
35. Xie, Z., Wroblewska, L., Prochazka, L., Weiss, R. & Benenson, Y. Multi-input RNAi-based logic circuit for identification of specific cancer cells. Science 333, 1307-1311 (2011).
36. Lucks, J. B., Qi, L., Mutalik, V. K., Wang, D. & Arkin, A. P. Versatile RNA-sensing transcriptional regulators for engineering genetic networks. Proc. Natl Acad. Sci. USA 108, 8617-8622 (2011).
37. Cho, E. J., Lee, J.-W. & Ellington, A. D. Applications of aptamers as sensors. Annu. Rev. Anal. Chem. 2, 241-264 (2009).
38. Famulok, M., Hartig, J. S. & Mayer, G. Functional aptamers and aptazymes in biotechnology, diagnostics, and therapy. Chem. Rev. 107, 3715-3743 (2007). (Pubitemid 47534316)
39. Win, M. N. & Smolke, C. D. A modular and extensible RNA-based gene-regulatory platform for engineering cellular function. Proc. Natl Acad. Sci. USA 104, 14283-14288 (2007). (Pubitemid 350003254)
40. Win, M. N. & Smolke, C. D. Higher-order cellular information processing with synthetic RNA devices. Science 322, 456-460 (2008).
41. Ausländer, S., Ketzer, P. & Hartig, J. S. A ligand-dependent hammerhead ribozyme switch for controlling mammalian gene expression. Mol. Biosyst. 6, 807-814 (2010).
42. Joyce, G. F. Forty years of in vitro evolution. Angew. Chem. Int. Edn Engl. 46, 6420-6436 (2007). (Pubitemid 47340165)
43. Culler, S. J., Hoff, K. G. & Smolke, C. D. Reprogramming cellular behavior with RNA controllers responsive to endogenous proteins. Science 330, 1251-1255 (2010).
44. Vuyisich, M. & Beal, P. A. Controlling protein activity with ligand-regulated RNA aptamers. Chem. Biol. 9, 907-913 (2002). (Pubitemid 35240910)
45. Hunsicker, A. et al. An RNA aptamer that induces transcription. Chem. Biol. 16, 173-180 (2009).
46. Skerker, J. M. et al. Rewiring the specificity of two-component signal transduction systems. Cell 133, 1043-1054 (2008). (Pubitemid 351787742)
47. Levskaya, A. et al. Synthetic biology: engineering Escherichia coli to see light. Nature 438, 441-442 (2005). (Pubitemid 41742007)
48. Tabor, J. J. Levskaya, A. & Voigt, C. A. Multichromatic control of gene expression in Escherichia coli. J. Mol. Biol. 405, 315-324 (2010).
49. Toettcher, J. E., Voigt, C. A., Weiner, O. D. & Lim, W. A. The promise of optogenetics in cell biology: interrogating molecular circuits in space and time. Nature Methods 8, 35-38 (2011).
50. Fenno, L., Yizhar, O. & Deisseroth, K. The development and application of optogenetics. Annu. Rev. Neurosci. 34, 389-412 (2010).
51. Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nature Neurosci. 8, 1263-1268 (2005). (Pubitemid 43348147)
52. Levskaya, A. Weiner, O. D., Lim, W. A. & Voigt, C. A. Spatiotemporal control of cell signalling using a light-switchable protein interaction. Nature 461, 997-1001 (2009).
53. Wu, Y. I. et al. A genetically encoded photoactivatable Rac controls the motility of living cells. Nature 461, 104-108 (2009).
54. Airan, R. D., Thompson, K. R., Fenno, L. E., Bernstein, H. & Deisseroth, K. Temporally precise in vivo control of intracellular signalling. Nature 458, 1025-1029 (2009).
55. Gautier, A., Deiters, A. & Chin, J. W. Light-activated kinases enable temporal dissection of signaling networks in living cells. J. Am. Chem. Soc. 133, 2124-2127 (2011).
56. Magnus, C. J. et al. Chemical and genetic engineering of selective ion channel-ligand interactions. Science 333, 1292-1296 (2011).
57. Pei, Y., Rogan, S. C., Yan, F. & Roth, B. L. Engineered GPCRs as tools to modulate signal transduction. Physiology 23, 313-321 (2008).
58. Dong, S., Rogan, S. C. & Roth, B. L. Directed molecular evolution of DREADDs: a generic approach to creating next-generation RASSLs. Nature Protoc. 5, 561-573 (2010).
59. Lim, W. A. Designing customized cell signalling circuits. Nature Rev. Mol. Cell Biol. 11, 393-403 (2010).
60. Burrill, D. R. & Silver, P. A. Making cellular memories. Cell 140, 13-18 (2010).
61. Purcell, O., Savery, N. J., Grierson, C. S. & di Bernardo, M. A comparative analysis of synthetic genetic oscillators. J. R. Soc. Interface 7, 1503-1524 (2010).
62. Atkinson, M. R., Savageau, M. A., Myers, J. T. & Ninfa, A. J. Development of genetic circuitry exhibiting toggle switch or oscillatory behavior in Escherichia coli. Cell 113, 597-607 (2003). (Pubitemid 36694185)
63. Stricker, J. et al. A fast, robust and tunable synthetic gene oscillator. Nature 456, 516-519 (2008). (Pubitemid 352759003)
64. Danino, T., Mondragón-Palomino, O., Tsimring, L. & Hasty, J. A synchronized quorum of genetic clocks. Nature 463, 326-330 (2010).
65. Tigges, M., Marquez-Lago, T. T., Stelling, J. & Fussenegger, M. A tunable synthetic mammalian oscillator. Nature 457, 309-312 (2009).
66. Kramer, B. P. et al. An engineered epigenetic transgene switch in mammalian cells. Nature Biotech. 22, 867-870 (2004). (Pubitemid 38886606)
67. Ham, T. S., Lee, S. K., Keasling, J. D. & Arkin, A. P. Design and construction of a double inversion recombination switch for heritable sequential genetic memory. PLoS ONE 3, e2815 (2008).
68. Friedland, A. E. et al. Synthetic gene networks that count. Science 324, 1199-1202 (2009).
69. Brenner, K., You, L. & Arnold, F. H. Engineering microbial consortia: a new frontier in synthetic biology. Trends Biotechnol. 26, 483-489 (2008).
70. Pai, A., Tanouchi, Y., Collins, C. H. & You, L. Engineering multicellular systems by cell-cell communication. Curr. Opin. Biotechnol. 20, 461-470 (2009).
71. Basu, S., Gerchman, Y., Collins, C. H., Arnold, F. H. & Weiss, R. A synthetic multicellular system for programmed pattern formation. Nature 434, 1130-1134 (2005). (Pubitemid 40663491)
72. Liu, C. et al. Sequential establishment of stripe patterns in an expanding cell population. Science 334, 238-241 (2011).
73. You, L., Cox, R. S., Weiss, R. & Arnold, F. H. Programmed population control by cell-cell communication and regulated killing. Nature 428, 868-871 (2004). (Pubitemid 38529503)
74. Balagaddé, F. K. et al. A synthetic Escherichia coli predator-prey ecosystem. Mol. Systems Biol. 4, 187 (2008).
75. Weber, W., Daoud-El Baba, M. & Fussenegger, M. Synthetic ecosystems based on airborne inter-and intrakingdom communication. Proc. Natl Acad. Sci. USA 104, 10435-10440 (2007). (Pubitemid 47185683)
76. Tamsir, A. Tabor, J. J. & Voigt, C. A. Robust multicellular computing using genetically encoded NOR gates and chemical "wires". Nature 469, 212-215 (2011).
77. Tabor, J. J. et al. A synthetic genetic edge detection program. Cell 137, 1272-1281 (2009).
78. Collins, C. H., Leadbetter, J. R. & Arnold, F. H. Dual selection enhances the signaling specificity of a variant of the quorum-sensing transcriptional activator LuxR. Nature Biotech. 24, 708-712 (2006). (Pubitemid 43882123)
79. Sturme, M. H. J. et al. Cell to cell communication by autoinducing peptides in gram-positive bacteria. Antonie van Leeuwenhoek 81, 233-243 (2002). (Pubitemid 35314612)
80. Dunny, G. M. & Leonard, B. A. Cell-cell communication in Gram-positive bacteria. Annu. Rev. Microbiol. 51, 527-564 (1997). (Pubitemid 27433058)
81. Clarke, E. J. & Voigt, C. A. Characterization of combinatorial patterns generated by multiple two-component sensors in E. coli that respond to many stimuli. Biotechnol. Bioeng. 108, 666-675 (2011).
82. Ninfa, A. J. Use of two-component signal transduction systems in the construction of synthetic genetic networks. Curr. Opin. Microbiol. 13, 240-245 (2010).
83. Shou, W., Ram, S. & Vilar, J. M. G. Synthetic cooperation in engineered yeast populations. Proc. Natl Acad. Sci. USA 104, 1877-1882 (2007). (Pubitemid 46239872)
84. Weber, W., Schuetz, M., Dénervaud, N. & Fussenegger, M. A synthetic metabolite-based mammalian inter-cell signaling system. Mol. Biosyst. 5, 757-763 (2009).
85. Weber, W. et al. Gas-inducible transgene expression in mammalian cells and mice. Nature Biotech. 22, 1440-1444 (2004). (Pubitemid 39482865)
86. Wang, W.-D., Chen, Z.-T., Kang, B.-G. & Li, R. Construction of an artificial intercellular communication network using the nitric oxide signaling elements in mammalian cells. Exp. Cell Res. 314, 699-706 (2008).
87. Chen, M.-T. & Weiss, R. Artificial cell-cell communication in yeast Saccharomyces cerevisiae using signaling elements from Arabidopsis thaliana. Nature Biotech. 23, 1551-1555 (2005). (Pubitemid 41752933)
88. Park, S.-H. Zarrinpar, A. & Lim, W. a Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms. Science 299, 1061-1064 (2003). (Pubitemid 36222931)
89. Dueber, J. E. Mirsky, E. A. & Lim, W. A. Engineering synthetic signaling proteins with ultrasensitive input/output control. Nature Biotech. 25, 660-662 (2007). (Pubitemid 46897205)
90. Bashor, C. J. Helman, N. C., Yan, S. & Lim, W. A. Using engineered scaffold interactions to reshape MAP kinase pathway signaling dynamics. Science 319, 1539-1543 (2008). (Pubitemid 351398185)
91. Peisajovich, S. G., Garbarino, J. E., Wei, P. & Lim, W. A. Rapid diversification of cell signaling phenotypes by modular domain recombination. Science 328, 368-372 (2010).
92. Alon, U. Network motifs: theory and experimental approaches. Nature Rev. Genet. 8, 450-461 (2007). (Pubitemid 46789247)
93. Guet, C. C., Elowitz, M. B., Hsing, W. & Leibler, S. Combinatorial synthesis of genetic networks. Science 296, 1466-1470 (2002). (Pubitemid 34553091)
94. Francois, P., Hakim, V. & Siggia, E. D. Deriving structure from evolution: metazoan segmentation. Mol. Syst. Biol. 3, 154 (2007).
95. François, P. & Hakim, V. Design of genetic networks with specified functions by evolution in silico. Proc. Natl Acad. Sci. USA 101, 580-585 (2004). (Pubitemid 38084679)
96. Ellis, T., Wang, X. & Collins, J. J. Diversity-based, model-guided construction of synthetic gene networks with predicted functions. Nature Biotech. 27, 465-471 (2009).
97. Randall, A., Guye, P., Gupta, S., Duportet, X. & Weiss, R. Design and connection of robust genetic circuits. Meth. Enzymol. 497, 159-186 (2011).
98. Silva-Rocha, R. & de Lorenzo, V. Noise and robustness in prokaryotic regulatory networks. Annu. Rev. Microbiol. 64, 257-275 (2010).
99. Balázsi, G., van Oudenaarden, A. & Collins, J. J. Cellular decision making and biological noise: from microbes to mammals. Cell 144, 910-925 (2011).
100. Regot, S. et al. Distributed biological computation with multicellular engineered networks. Nature 469, 207-211 (2011).
101. Del Vecchio, D., Ninfa, A. J. & Sontag, E. D. Modular cell biology: retroactivity and insulation. Mol. Systems Biol. 4, 161 (2008).
102. Mukherji, S. et al. MicroRNAs can generate thresholds in target gene expression. Nature Genet. 43, 854-859 (2011).
103. Nandagopal, N. & Elowitz, M. B. Synthetic biology: integrated gene circuits. Science 333, 1244-1248 (2011).
104. Ye, H., Daoud-El Baba, M., Peng, R.-W. & Fussenegger, M. A synthetic optogenetic transcription device enhances blood-glucose homeostasis in mice. Science 332, 1565-1568 (2011).
105. Anderson, J. C. Clarke, E. J., Arkin, A. P. & Voigt, C. A. Environmentally controlled invasion of cancer cells by engineered bacteria. J. Mol. Biol. 355, 619-627 (2006). (Pubitemid 41817623)
106. Haseltine, E. L. & Arnold, F. H. Synthetic gene circuits: design with directed evolution. Annu. Rev. Biophys. Biomol. Struct. 36, 1-19 (2007). (Pubitemid 46998107)
107. Röthlisberger, D. et al. Kemp elimination catalysts by computational enzyme design. Nature 453, 190-195 (2008). (Pubitemid 351667979)
108. Voigt, C. a, Mayo, S. L., Arnold, F. H. & Wang, Z. G. Computational method to reduce the search space for directed protein evolution. Proc. Natl Acad. Sci. USA 98, 3778-3783 (2001). (Pubitemid 32249848)
109. Lutz, S. & Patrick, W. M. Novel methods for directed evolution of enzymes: quality, not quantity. Curr. Opin. Biotechnol. 15, 291-297 (2004). (Pubitemid 39024689)
110. Katz, R. H. Contemporary Logic Design. (Benjamin Cummings, 1994).
111. Corey, E. J. The logic of chemical synthesis: multistep synthesis of complex carbogenic molecules (Nobel Lecture). Angew. Chem. Int. Edn Engl. 30, 455-465 (1991).
112. Corey, E., Long, A. & Rubenstein, S. Computer-assisted analysis in organic synthesis. Science 228, 408-418 (1985).
113. Hoogenboom, H. R. Selecting and screening recombinant antibody libraries. Nature Biotech. 23, 1105-1116 (2005). (Pubitemid 41486392)
114. Hackel, B. J., Kapila, A. & Wittrup, K. D. Picomolar affinity fibronectin domains engineered utilizing loop length diversity, recursive mutagenesis, and loop shuffling. J. Mol. Biol. 381, 1238-1252 (2008).
115. Boersma, Y. L. & Plückthun, A. DARPins and other repeat protein scaffolds: advances in engineering and applications. Curr. Opin. Biotechnol. 22, 849-57 (2011).
116. Leisner, M., Bleris, L., Lohmueller, J., Xie, Z. & Benenson, Y. Rationally designed logic integration of regulatory signals in mammalian cells. Nature Nanotechnol. 5, 1-5 (2010).
117. Cermak, T. et al. Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic Acids Res. 39, e82 (2011).
118. Miller, J. C. et al. A TALE nuclease architecture for efficient genome editing. Nature Biotech. 29, 143-148 (2011).
119. Conklin, B. R. et al. Engineering GPCR signaling pathways with RASSLs. Persp. 5, 673-678 (2008).
120. Gunaydin, L. a. et al. Ultrafast optogenetic control. Nature Neurosci. 13, 387-392 (2010).
121. Weissman, K. J. & Leadlay, P. F. Combinatorial biosynthesis of reduced polyketides. Nature Rev. Microbiol. 3, 925-936 (2005). (Pubitemid 43078156)
122. Cane, D. E. Harnessing the biosynthetic code: combinations, permutations, and mutations. Science 282, 63-68 (1998). (Pubitemid 28471127)
123. Jiang, L. et al. De novo computational design of retro-aldol enzymes. Science 319, 1387-1391 (2008). (Pubitemid 351354873)
124. Richter, F., Leaver-Fay, A., Khare, S. D., Bjelic, S. & Baker, D. De novo enzyme design using Rosetta3. PLoS ONE 6, e19230 (2011).
125. Kramer, B. P., Fischer, C. & Fussenegger, M. BioLogic gates enable logical transcription control in mammalian cells. Biotechnol. Bioeng. 87, 478-484 (2004). (Pubitemid 39150049)
126. Tigges, M., Dénervaud, N., Greber, D., Stelling, J. & Fussenegger, M. A synthetic low-frequency mammalian oscillator. Nucleic Acids Res. 38, 2702-2711 (2010).
127. Swinburne, I., Miguez, D. G., Landgraf, D. & Silver, P. Intron length increases oscillatory periods of gene expression in animal cells. Genes Dev. 22, 2342-2346 (2008).
128. Gerhart, J. & Kirschner, M. The theory of facilitated variation. Proc. Natl Acad. Sci. USA 104, 8582-8589 (2007). (Pubitemid 47175450)
129. Yuh, C. H., Bolouri, H. & Davidson, E. H. Genomic cis-regulatory logic: experimental and computational analysis of a sea urchin gene. Science 279, 1896-1902 (1998). (Pubitemid 28168638)
130. Green, J. & Langer, R. A combinatorial polymer library approach yields insight into nonviral gene delivery. Acc. Chem. Res. 41, 749-759 (2008).
131. Kauffman, S. A. The Origins of Order: Self-Organization and Selection in Evolution (Oxford Univ. Press, 1993).
132. Kauffman, S. A. & Weinberger, E. D. The NK model of rugged fitness landscapes and its application to maturation of the immune response. J. Theor. Biol. 141, 211-245 (1989). (Pubitemid 20036173)
133. Funahashi, A. et al. CellDesigner 3.5: a versatile modeling tool for biochemical networks. Proc. IEEE 96, 1254-1265 (2008).
134. Pedersen, M. & Phillips, A. Towards programming languages for genetic engineering of living cells. J. R. Soc. Interface 6, S437-S450 (2009).
135. Czar, M. J., Cai, Y. & Peccoud, J. Writing DNA with GenoCAD. Nucleic Acids Res. 37, W40-W47 (2009).
136. Mirschel, S., Steinmetz, K., Rempel, M. & Ginkel, M. PROMOT: modular modeling for systems biology. Bioinformatics 25, 687-689 (2009).
137. Hill, A. D., Tomshine, J. R., Weeding, E. M. B., Sotiropoulos, V. & Kaznessis, Y. N. SynBioSS: the synthetic biology modeling suite. Bioinformatics 24, 2551-2553 (2008).
138. Chandran, D., Bergmann, F. T. & Sauro, H. M. TinkerCell: modular CAD tool for synthetic biology. J. Biol. Eng. 29, 19 (2009).
139. Rodrigo, G., Carrera, J. & Jaramillo, A. Genetdes: automatic design of transcriptional networks. Bioinformatics 23, 1857-1858 (2007). (2009).
140. Dasika, M. S. & Maranas, C. D. OptCircuit: an optimization based method for computational design of genetic circuits. BMC Systems Biol. 2, 24 (2008).
141. Batt, G., Yordanov, B., Weiss, R. & Belta, C. Robustness analysis and tuning of synthetic gene networks. Bioinformatics 23, 2415-2422 (2007). (Pubitemid 47423839)
142. Zuker, M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 31, 3406-3415 (2003). (Pubitemid 37442169)
143. Hoops, S. et al. COPASI-a COmplex PAthway SImulator. Bioinformatics 22, 3067-3074 (2006).
144. Merks, R. & Glazier, J. A cell-centered approach to developmental biology. Physica A 352, 113-130 (2005). (Pubitemid 40584061)
145. Villalobos, A., Ness, J. E., Gustafsson, C., Minshull, J. & Govindarajan, S. Gene Designer: a synthetic biology tool for constructing artificial DNA segments. BMC Bioinformat. 7, 285 (2006).
146. Richardson, S. M., Wheelan, S. J., Yarrington, R. M. & Boeke, J. D. GeneDesign: rapid, automated design of multikilobase synthetic genes. Genome Res. 16, 550-556 (2006).
147. Xia, B. et al. Developer's and user's guide to Clotho v2.0 A software platform for the creation of synthetic biological systems. Meth. Enzymol. 498, 97-135 (2011).