Mammalian synthetic biology: Emerging medical applications

Journal of the Royal Society Interface

Volumn 12, Issue 106, 2015, Pages

  Kis, Zoltán ^a   Pereira, Hugo Sant'Ana ^a   Homma, Takayuki ^a   Pedrigi, Ryan M ^a   Krams, Rob ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

Gene therapy; Mammalian cells; Synthetic biology

Indexed keywords

BIOLOGY; COMPLEX NETWORKS; GENES; MAMMALS; MEDICAL APPLICATIONS; NETWORKS (CIRCUITS);

BIO-MANUFACTURING; BIOLOGICAL COMPONENTS; BOOLEAN LOGIC GATES; MAMMALIAN CELLS; POST-TRANSCRIPTIONAL; REGULATORY NETWORK; SYNTHETIC BIOLOGY; SYNTHETIC GENE NETWORK;

GENE THERAPY;

ANTIBIOTIC AGENT; MESSENGER RNA; SYNTHETIC DNA;

ANTIBIOTIC RESISTANCE; BIOMEDICAL ENGINEERING; DRUG DEVELOPMENT; GENE REGULATORY NETWORK; GENE SWITCHING; GENETIC ENGINEERING; INFORMATION SCIENCE; MAMMAL; MAMMAL CELL; MOLECULAR BIOLOGY; NONHUMAN; PROTEIN PROCESSING; REVIEW; SYNTHETIC BIOLOGY; TRANSLATION INITIATION; ANIMAL; BIOTECHNOLOGY; DRUG DELIVERY SYSTEM; GENETICS; TRENDS;

MAMMALIA;

ANIMALS; BIOTECHNOLOGY; DRUG DELIVERY SYSTEMS; DRUG DISCOVERY; GENE REGULATORY NETWORKS; GENES, SYNTHETIC; MAMMALS; SYNTHETIC BIOLOGY;

EID: 84929500833     PISSN: 17425689     EISSN: 17425662     Source Type: Journal    
DOI: 10.1098/rsif.2014.1000     Document Type: Review

References (190)

1. Elowitz MB, Leibler S. 2000 A synthetic oscillatory network of transcriptional regulators. Nature 403, 335-338. (doi:10.1038/35002125)
2. Gardner TS, Cantor CR, Collins JJ. 2000 Construction of a genetic toggle switch in Escherichia coli. Nature 403, 339-342. (doi:10.1038/35002131)
3. Lienert F, Lohmueller JJ, Garg A, Silver PA. 2014 Synthetic biology in mammalian cells: next generation research tools and therapeutics. Nat. Rev. Mol. Cell Biol. 15, 95-107. (doi:10.1038/nrm3738)
4. Weber W, Fussenegger M. 2009 Engineering of synthetic mammalian gene networks. Chem. Biol. 16, 287-297. (doi:10.1016/j.chembiol.2009.02.005)
5. Tigges M, Fussenegger M. 2009 Recent advances in mammalian synthetic biology-design of synthetic transgene control networks. Curr. Opin. Biotechnol. 20, 449-460. (doi:10.1016/j.copbio.2009.07.009)
6. Kwok R. 2010 Five hard truths for synthetic biology. Nature 463, 288-290. (doi:10.1038/463288a)
7. May T, Eccleston L, Herrmann S, Hauser H, Goncalves J, Wirth D. 2008 Bimodal and hysteretic expression in mammalian cells from a synthetic gene circuit. PloS ONE 3, e2372. (doi:10.1371/journal.pone.0002372)
8. Fraser HB, Hirsh AE, Giaever G, Kumm J, Eisen MB. 2004 Noise minimization in eukaryotic gene expression. PLoS Biol. 2, e137. (doi:10.1371/journal.pbio.0020137)
9. Blake WJ, KÆrn M, Cantor CR, Collins JJ. 2003 Noise in eukaryotic gene expression. Nature 422, 633-637. (doi:10.1038/nature01546)
10. Bashor CJ, Helman NC, Yan SD, Lim WA. 2008 Using engineered scaffold interactions to reshape map kinase pathway signaling dynamics. Science 319, 1539-1543. (doi:10.1126/science.1151153)
11. Gossen M, Bujard H. 1992 Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc. Natl Acad. Sci. USA 89, 5547-5551. (doi:10.1073/pnas.89.12.5547)
12. Fussenegger M, Morris RP, Fux C, Rimann M, von Stockar B, Thompson CJ, Bailey JE. 2000 Streptogramin-based gene regulation systems for mammalian cells. Nat. Biotechnol. 18, 1203-1208. (doi:10.1038/81208)
13. Kalos M, June CH. 2013 Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology. Immunity 39, 49-60. (doi:10.1016/j.immuni.2013.07.002)
14. June CH, Maus MV, Plesa G, Johnson LA, Zhao Y, Levine BL, Grupp SA, Porter DL. 2014 Engineered T cells for cancer therapy. Cancer Immunol. Immunother. 63, 969-975. (doi:10.1007/s00262-014-1568-1)
15. Auslander S, Fussenegger M. 2013 From gene switches to mammalian designer cells: present and future prospects. Trends Biotechnol. 31, 155-168. (doi:10.1016/j.tibtech.2012.11.006)
16. Ruder WC, Lu T, Collins JJ. 2011 Synthetic biology moving into the clinic. Science 333, 1248-1252. (doi:10.1126/science.1206843)
17. Cameron DE, Bashor CJ, Collins JJ. 2014 A brief history of synthetic biology. Nat. Rev. Microbiol. 12, 381-390. (doi:10.1038/nrmicro3239)
18. Khalil AS, Collins JJ. 2010 Synthetic biology: applications come of age. Nat. Rev. Genet. 11, 367-379. (doi:10.1038/nrg2775)
19. Liang FS, Ho WQ, Crabtree GR. 2011 Engineering the ABA plant stress pathway for regulation of induced proximity. Sci. Signal. 4, rs2. (doi:10.1126/scisignal.2001449)
20. Weber W, Rimann M, Spielmann M, Keller B, Daoud-El Baba M, Aubel D, Weber CC, Fussenegger M. 2004 Gas-inducible transgene expression in mammalian cells and mice. Nat. Biotechnol. 22, 1440-1444. (doi:10.1038/nbt1021)
21. Hartenbach S, Daoud-El Baba M, Weber W, Fussenegger M. 2007 An engineered L-arginine sensor of Chlamydia pneumoniae enables arginine-adjustable transcription control in mammalian cells and mice. Nucleic Acids Res. 35, e136. (doi:10.1093/nar/gkm652)
22. Rossger K, Charpin-El-Hamri G, Fussenegger M. 2014 Bile acid-controlled transgene expression in mammalian cells and mice. Metab. Eng. 21, 81-90. (doi:10.1016/j.ymben.2013.11.003)
23. Weber W, Bacchus W, Daoud-El Baba M, Fussenegger M. 2007 Vitamin H-regulated transgene expression in mammalian cells. Nucleic Acids Res. 35, e116. (doi:10.1093/nar/gkm466)
24. Weber W, Lienhart C, Baba MD, Fussenegger M. 2009 A biotin-triggered genetic switch in mammalian cells and mice. Metab. Eng. 11, 117-124. (doi:10.1016/j.ymben.2008.12.001)
25. Kennedy MJ, Hughes RM, Peteya LA, Schwartz JW, Ehlers MD, Tucker CL. 2010 Rapid blue-light-mediated induction of protein interactions in living cells. Nat. Methods 7, 973-975. (doi:10.1038/nmeth.1524)
26. Xie M, Ye H, Hamri GC, Fussenegger M. 2014 Antagonistic control of a dual-input mammalian gene switch by food additives. Nucleic Acids Res. 42, e116. (doi:10.1093/nar/gku545)
27. Mullick A et al. 2006 The cumate gene-switch: a system for regulated expression in mammalian cells. BMC Biotechnol. 6, 43. (doi:10.1186/1472-6750-6-43)
28. No D, Yao TP, Evans RM. 1996 Ecdysone-inducible gene expression in mammalian cells and transgenic mice. Proc. Natl Acad. Sci. USA 93, 3346-3351. (doi:10.1073/pnas.93.8.3346)
29. Palli SR, Kapitskaya MZ, Potter DW. 2005 The influence of heterodimer partner ultraspiracle/retinoid X receptor on the function of ecdysone receptor. FEBS J. 272, 5979-5990. (doi:10.1111/j.1742-4658.2005.05003.x)
30. Weber W, Luzi S, Karlsson M, Sanchez-Bustamante CD, Frey U, Hierlemann A, Fussenegger M. 2009 A synthetic mammalian electro-genetic transcription circuit. Nucleic Acids Res. 37, e33. (doi:10.1093/nar/gkp014)
31. Liang J, McLachlan MJ, Zhao H. 2013 Orthogonal control of endogenous gene expression in mammalian cells using synthetic ligands. Biotechnol. Bioeng. 110, 1419-1429. (doi:10.1002/bit.24807)
32. Weber W et al. 2002 Macrolide-based transgene control in mammalian cells and mice. Nat. Biotechnol. 20, 901-907. (doi:10.1038/nbt731)
33. Weber W, Schoenmakers R, Keller B, Gitzinger M, Grau T, Daoud-El Baba M, Sander P, Fussenegger M. 2008 A synthetic mammalian gene circuit reveals antituberculosis compounds. Proc. Natl Acad. Sci. USA 105, 9994-9998. (doi:10.1073/pnas.0800663105)
34. Braselmann S, Graninger P, Busslinger M. 1993 A selective transcriptional induction system for mammalian cells based on Gal4-estrogen receptor fusion proteins. Proc. Natl Acad. Sci. USA 90, 1657-1661. (doi:10.1073/pnas.90.5.1657)
35. Wang Y, Xu J, Pierson T, O0 Malley BW, Tsai SY. 1997 Positive and negative regulation of gene expression in eukaryotic cells with an inducible transcriptional regulator. Gene Therapy 4, 432-441. (doi:10.1038/sj.gt.3300402)
36. Wang YL, Omalley BW, Tsai SY, Omalley BW. 1994 A regulatory system for use in gene-transfer. Proc. Natl Acad. Sci. USA 91, 8180-8184. (doi:10.1073/pnas.91.17.8180)
37. Liberles SD, Diver ST, Austin DJ, Schreiber SL. 1997 Inducible gene expression and protein translocation using nontoxic ligands identified by a mammalian three-hybrid screen. Proc. Natl Acad. Sci. USA 94, 7825-7830. (doi:10.1073/pnas.94.15.7825)
38. Collingwood TN, Butler A, Tone Y, Clifton-Bligh RJ, Parker MG, Chatterjee VK. 1997 Thyroid hormone-mediated enhancement of heterodimer formation between thyroid hormone receptor beta and retinoid X receptor. J. Biol. Chem. 272, 13 060-13 065. (doi:10.1074/jbc.272.20.13060)
39. Zhao HF, Boyd J, Jolicoeur N, Shen SH. 2003 A coumermycin/novobiocin-regulated gene expression system. Hum. Gene Therapy 14, 1619-1629. (doi:10.1089/104303403322542266)
40. Roscilli G, Rinaudo CD, Cimino M, Sporeno E, Lamartina S, Ciliberto G, Toniatti C. 2002 Long-term and tight control of gene expression in mouse skeletal muscle by a new hybrid human transcription factor. Mol. Therapy J. Am. Soc. Gene Therapy 6, 653-663. (doi:10.1016/S1525-0016(02) 90717-3)
41. Auslander D, Wieland M, Auslander S, Tigges M, Fussenegger M. 2011 Rational design of a small molecule-responsive intramer controlling transgene expression in mammalian cells. Nucleic Acids Res. 39, e155. (doi:10.1093/nar/gkr829)
42. Wyborski DL, Short JM. 1991 Analysis of inducers of the E. coli lac repressor system in mammalian cells and whole animals. Nucleic acids Res. 19, 4647-4653. (doi:10.1093/nar/19.17.4647)
43. Hu MC, Davidson N. 1987 The inducible lac operator-repressor system is functional in mammalian cells. Cell 48, 555-566. (doi:10.1016/0092-8674(87)90234-0)
44. Hu MC, Davidson NA. 1990 Combination of derepression of the lac operator-repressor system with positive induction by glucocorticoid and metal ions provides a high-level-inducible gene expression system based on the human metallothionein-iia promoter. Mol. Cell Biol. 10, 6141-6151.
45. Brown M, Figge J, Hansen U, Wright C, Jeang KT, Khoury G, Livingston DM, Roberts TM. 1987 Lac repressor can regulate expression from a hybrid sv40 early promoter containing a lac operator in animal cells. Cell 49, 603-612. (doi:10.1016/0092-8674(87)90536-8)
46. Cronin CA, Gluba W, Scrable H. 2001 The lac operator-repressor system is functional in the mouse. Genes Dev. 15, 1506-1517. (doi:10.1101/gad.892001)
47. Yazawa M, Sadaghiani AM, Hsueh B, Dolmetsch RE. 2009 Induction of protein - protein interactions in live cells using light. Nat. Biotechnol. 27, 941-945. (doi:10.1038/nbt.1569)
48. Wang X, Chen X, Yang Y. 2012 Spatiotemporal control of gene expression by a light-switchable transgene system. Nat. Methods 9, 266-269. (doi:10.1038/nmeth.1892)
49. Malphettes L, Weber CC, El-Baba MD, Schoenmakers RG, Aubel D, Weber W, Fussenegger M. 2005 A novel mammalian expression system derived from components coordinating nicotine degradation in Arthrobacter nicotinovorans pAO1. Nucleic Acids Res. 33, e107. (doi:10.1093/nar/gni107)
50. Tascou S, Sorensen TK, Glenat V, Wang M, Lakich MM, Darteil R, Vigne E, Thuillier V. 2004 Stringent rosiglitazone-dependent gene switch in muscle cells without effect on myogenic differentiation. Mol. Therapy 9, 637-649. (doi:10.1016/j.ymthe.2004.02.013)
51. Gitzinger M, Kemmer C, El-Baba MD, Weber W, Fussenegger M. 2009 Controlling transgene expression in subcutaneous implants using a skin lotion containing the apple metabolite phloretin. Proc. Natl Acad. Sci. USA 106, 10 638-10 643. (doi:10.1073/pnas.0901501106)
52. Weber W, Link N, Fussenegger M. 2006 A genetic redox sensor for mammalian cells. Metab. Eng. 8, 273-280. (doi:10.1016/j.ymben.2005.12.004)
53. Weber W et al. 2003 Streptomyces-derived quorum-sensing systems engineered for adjustable transgene expression in mammalian cells and mice. Nucleic acids Res. 31, e71. (doi:10.1093/nar/gng071)
54. Folcher M, Xie M, Spinnler A, Fussenegger M. 2013 Synthetic mammalian trigger-controlled bipartite transcription factors. Nucleic Acids Res. 41, e134. (doi:10.1093/nar/gkt405)
55. Weber W et al. 2003 Conditional human VEGF-mediated vascularization in chicken embryos using a novel temperature-inducible gene regulation (TIGR) system. Nucleic Acids Res. 31, e69. (doi:10.1093/nar/gng069)
56. Neddermann P, Gargioli C, Muraglia E, Sambucini S, Bonelli F, De Francesco R, Cortese R. 2003 A novel, inducible, eukaryotic gene expression system based on the quorum-sensing transcription factor TraR. EMBO Rep. 4, 159-165. (doi:10.1038/sj.embor.embor734)
57. Urlinger S, Baron U, Thellmann M, Hasan MT, Bujard H, Hillen W. 2000 Exploring the sequence space for tetracycline-dependent transcriptional activators: novel mutations yield expanded range and sensitivity. Proc. Natl Acad. Sci. USA 97, 7963-7968. (doi:10.1073/pnas.130192197)
58. Bacchus W, Lang M, El-Baba MD, Weber W, Stelling J, Fussenegger M. 2012 Synthetic two-way communication between mammalian cells. Nat. Biotechnol. 30, 991-996. (doi:10.1038/nbt.2351)
59. Kemmer C, Gitzinger M, Daoud-El Baba M, Djonov V, Stelling J, Fussenegger M. 2010 Self-sufficient control of urate homeostasis in mice by a synthetic circuit. Nat. Biotechnol. 28, 355-360. (doi:10.1038/nbt.1617)
60. Gitzinger M, Kemmer C, Fluri DA, El-Baba MD, Weber W, Fussenegger M. 2012 The food additive vanillic acid controls transgene expression in mammalian cells and mice. Nucleic Acids Res. 40, e37. (doi:10.1093/nar/gkr1251)
61. Magnenat L, Schwimmer LJ, Barbas III CF, 2008 Drug-inducible and simultaneous regulation of endogenous genes by single-chain nuclear receptor-based zinc-finger transcription factor gene switches. Gene Therapy 15, 1223-1232. (doi:10.1038/gt.2008.96)
62. Rivera VM et al. 1996 A humanized system for pharmacologic control of gene expression. Nature Med. 2, 1028-1032. (doi:10.1038/nm0996-1028)
63. Beerli RR, Schopfer U, Dreier B, Barbas III CF. 2000 Chemically regulated zinc finger transcription factors. J. Biol. Chem. 275, 32 617-32 627. (doi:10.1074/jbc.M005108200)
64. Schwimmer LJ, Gonzalez B, Barbas III CF. 2012 Benzoate X receptor zinc-finger gene switches for drug-inducible regulation of transcription. Gene Therapy 19, 458-462. (doi:10.1038/gt.2011.112)
65. An CI, Trinh VB, Yokobayashi Y. 2006 Artificial control of gene expression in mammalian cells by modulating RNA interference through aptamer - small molecule interaction. RNA 12, 710-716. (doi:10.1261/rna.2299306)
66. Kumar D, An CI, Yokobayashi Y. 2009 Conditional RNA interference mediated by allosteric ribozyme. J. Am. Chem. Soc. 131, 13 906-13 907. (doi:10.1021/ja905596t)
67. Beisel CL, Chen YY, Culler SJ, Hoff KG, Smolke CD. 2011 Design of small molecule-responsive microRNAs based on structural requirements for drosha processing. Nucleic Acids Res. 39, 2981-2994. (doi:10.1093/nar/gkq954)
68. Culler SJ, Hoff KG, Smolke CD. 2010 Reprogramming cellular behavior with RNA controllers responsive to endogenous proteins. Science 330, 1251-1255. (doi:10.1126/science.1192128)
69. Ketzer P, Haas SF, Engelhardt S, Hartig JS, Nettelbeck DM. 2012 Synthetic riboswitches for external regulation of genes transferred by replication-deficient and oncolytic adenoviruses. Nucleic Acids Res. 40, e167. (doi:10.1093/nar/gks734)
70. Boorsma M, Nieba L, Koller D, Bachmann MF, Bailey JE, Renner WA. 2000 A temperature-regulated replicon-based DNA expression system. Nat. Biotechnol. 18, 429-432. (doi:10.1038/74493)
71. Szulc J, Wiznerowicz M, Sauvain MO, Trono D, Aebischer P. 2006 A versatile tool for conditional gene expression and knockdown. Nat. Methods 3, 109-116. (doi:10.1038/nmeth846)
72. Kim DS, Gusti V, Dery KJ, Gaur RK. 2008 Ligand-induced sequestering of branchpoint sequence allows conditional control of splicing. BMC Mol. Biol. 9, 23. (doi:10.1186/1471-2199-9-23)
73. Chen YY, Jensen MC, Smolke CD. 2010 Genetic control of mammalian T-cell proliferation with synthetic RNA regulatory systems. Proc. Natl Acad. Sci. USA 107, 8531-8536. (doi:10.1073/pnas.1001721107)
74. Auslander S, Ketzer P, Hartig JS. 2010 A ligand-dependent hammerhead ribozyme switch for controlling mammalian gene expression. Mol. Biosyst. 6, 807-814. (doi:10.1039/b923076a)
75. Werstuck G, Green MR. 1998 Controlling gene expression in living cells through small molecule - RNA interactions. Science 282, 296-298. (doi:10.1126/science.282.5387.296)
76. Hara T, Saito H, Inoue T. 2013 Directed evolution of a synthetic RNA - protein module to create a new translational switch. Chem. Commun. 49, 3833-3835. (doi:10.1039/c3cc38688k)
77. Kodama K, Komatsu S, Ueda Y, Takayama T, Yajima J, Nanto S, Matsuoka H, Saito S, Hirayama A. 2010 Stabilization and regression of coronary plaques treated with pitavastatin proven by angioscopy and intravascular ultrasound: the together trial. Circ. J. 74, 1922-1928. (doi:10.1253/circj.CJ-10-0038)
78. Stripecke R, Oliveira CC, McCarthy JE, Hentze MW. 1994 Proteins binding to 5′ untranslated region sites: a general mechanism for translational regulation of mRNAs in human and yeast cells. Mol. Cell. Biol. 14, 5898-5909. (doi:10.1128/MCB.14.9.5898)
79. Nishimura K, Fukagawa T, Takisawa H, Kakimoto T, Kanemaki M. 2009 An auxin-based degron system for the rapid depletion of proteins in nonplant cells. Nat. Methods 6, 917-922. (doi:10.1038/nmeth.1401)
80. Miyazaki Y, Imoto H, Chen LC, Wandless TJ. 2012 Destabilizing domains derived from the human estrogen receptor. J. Am. Chem. Soc. 134, 3942-3945. (doi:10.1021/ja209933r)
81. Rivera VM et al. 2000 Regulation of protein secretion through controlled aggregation in the endoplasmic reticulum. Science 287, 826-830. (doi:10.1126/science.287.5454.826)
82. Los GV et al. 2008 Halotag: a novel protein labeling technology for cell imaging and protein analysis. ACS Chem. Biol. Chem. Biol. 3, 373-382. (doi:10.1021/cb800025k)
83. Neklesa TK, Tae HS, Schneekloth AR, Stulberg MJ, Corson TW, Sundberg TB, Raina K, Holley SA, Crews CM. 2011 Small-molecule hydrophobic tagging-induced degradation of halotag fusion proteins. Nat. Chem. Biol. 7, 538-543. (doi:10.1038/nchembio.597)
84. Nomura Y, Zhou LL, Miu A, Yokobayashi Y. 2013 Controlling mammalian gene expression by allosteric hepatitis delta virus ribozymes. ACS Synth. Biol. 2, 684-689. (doi:10.1021/sb400037a)
85. Schneekloth Jr JS, Fonseca FN, Koldobskiy M, Mandal A, Deshaies R, Sakamoto K, Crews CM. 2004 Chemical genetic control of protein levels: selective in vivo targeted degradation. J. Am. Chem. Soc. 126, 3748-3754. (doi:10.1021/ja039025z)
86. Banaszynski LA, Chen LC, Maynard-Smith LA, Ooi AG, Wandless TJ. 2006 A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules. Cell 126, 995-1004. (doi:10.1016/j.cell.2006.07.025)
87. Bonger KM, Chen LC, Liu CW, Wandless TJ. 2011 Small-molecule displacement of a cryptic degron causes conditional protein degradation. Nat. Chem. Biol. 7, 531-537. (doi:10.1038/nchembio.598)
88. Iwamoto K, Hamada H, Eguchi Y, Okamoto M. 2011 Mathematical modeling of cell cycle regulation in response to DNA damage: exploring mechanisms of cell-fate determination. Biosystems 103, 384-391. (doi:10.1016/j.biosystems.2010.11.011)
89. Jacob F, Monod J. 1961 Genetic regulatory mechanisms in the synthesis of proteins. J. Mol. Biol. 3, 318-356. (doi:10.1016/S0022-2836(61)80072-7)
90. Yu J, Zhang L, Hwang PM, Rago C, Kinzler KW, Vogelstein B. 1999 Identification and classification of p53-regulated genes. Proc. Natl Acad. Sci. USA 96, 14 517-14 522. (doi:10.1073/pnas.96.25.14517)
91. Kistner A, Gossen M, Zimmermann F, Jerecic J, Ullmer C, Lubbert H, Bujard H. 1996 Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc. Natl Acad. Sci. USA 93, 10 933-10 938. (doi:10.1073/pnas.93.20.10933)
92. Gossen M, Freundlieb S, Bender G, Muller G, Hillen W, Bujard H. 1995 Transcriptional activation by tetracyclines in mammalian cells. Science 268, 1766-1769. (doi:10.1126/science.7792603)
93. Weber W, Fussenegger M. 2004 Approaches for trigger-inducible viral transgene regulation in gene-based tissue engineering. Curr. Opin. Biotechnol. 15, 383-391. (doi:10.1016/j.copbio.2004.07.003)
94. Weber W, Fussenegger M. 2006 Pharmacologic transgene control systems for gene therapy. J. Gene Med. 8, 535-556. (doi:10.1002/jgm.903)
95. Nordstrom JL. 2002 Antiprogestin-controllable transgene regulation in vivo. Curr. Opin. Biotechnol. 13, 453-458. (doi:10.1016/S0958-1669(02)00356-7)
96. Chong H, Ruchatz A, Clackson T, Rivera VM, Vile RG. 2002 A system for small-molecule control of conditionally replication-competent adenoviral vectors. Mol. Therapy J. Am. Soc. Gene Therapy 5, 195-203. (doi:10.1006/mthe.2002.0531)
97. Mittal V. 2004 Improving the efficiency of RNA interference in mammals. Nat. Rev. Genet. 5, 355-365. (doi:10.1038/nrg1323)
98. Weber F, Wagner V, Rasmussen SB, Hartmann R, Paludan SR. 2006 Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses. J. Virol. 80, 5059-5064. (doi:10.1128/JVI.80.10.5059-5064.2006)
99. Zhang H, Kolb FA, Brondani V, Billy E, Filipowicz W. 2002 Human dicer preferentially cleaves dsRNAs at their termini without a requirement for ATP. EMBO J. 21, 5875-5885. (doi:10.1093/emboj/cdf582)
100. Deans TL, Cantor CR, Collins JJ. 2007 A tunable genetic switch based on RNAi and repressor proteins for regulating gene expression in mammalian cells. Cell 130, 363-372. (doi:10.1016/j.cell.2007.05.045)
101. Mayer G. 2009 The chemical biology of aptamers. Angew. Chem. Int. Ed. Engl. 48, 2672-2689. (doi:10.1002/anie.200804643)
102. Saito H, Kobayashi T, Hara T, Fujita Y, Hayashi K, Furushima R, Inoue T. 2010 Synthetic translational regulation by an L7Ae-kink-turn RNP switch. Nat. Chem. Biol. 6, 71-78. (doi:10.1038/nchembio.273)
103. Iwamoto M, Bjorklund T, Lundberg C, Kirik D, Wandless TJ. 2010 A general chemical method to regulate protein stability in the mammalian central nervous system. Chem. Biol. 17, 981-988. (doi:10.1016/j.chembiol.2010.07.009)
104. Gogarten JP, Senejani AG, Zhaxybayeva O, Olendzenski L, Hilario E. 2002 Inteins: structure, function, and evolution. Annu. Rev. Microbiol. 56, 263-287. (doi:10.1146/annurev.micro.56.012302.160741)
105. Anraku Y, Mizutani R, Satow Y. 2005 Protein splicing: its discovery and structural insight into novel chemical mechanisms. IUBMB Life 57, 563-574. (doi:10.1080/15216540500215499)
106. Lockless SW, Muir TW. 2009 Traceless protein splicing utilizing evolved split inteins. Proc. Natl Acad. Sci. USA 106, 10 999-11 004. (doi:10.1073/pnas.0902964106)
107. Elleuche S, Poggeler S. 2010 Inteins, valuable genetic elements in molecular biology and biotechnology. Appl. Microbiol. Biotechnol. 87, 479-489. (doi:10.1007/s00253-010-2628-x)
108. Mootz HD, Muir TW. 2002 Protein splicing triggered by a small molecule. J. Am. Chem. Soc. 124, 9044-9045. (doi:10.1021/ja026769o)
109. Mootz HD, Blum ES, Tyszkiewicz AB, Muir TW. 2003 Conditional protein splicing: a new tool to control protein structure and function in vitro and in vivo. J. Am. Chem. Soc. 125, 10 561-10 569. (doi:10.1021/ja0362813)
110. Shi J, Muir TW. 2005 Development of a tandem protein trans-splicing system based on native and engineered split inteins. J. Am. Chem. Soc. 127, 6198-6206. (doi:10.1021/ja042287w)
111. Selgrade DF, Lohmueller JJ, Lienert F, Silver PA. 2013 Protein scaffold-activated protein transsplicing in mammalian cells. J. Am. Chem. Soc. 135, 7713-7719. (doi:10.1021/ja401689b)
112. Daniel R, Rubens JR, Sarpeshkar R, Lu TK. 2013 Synthetic analog computation in living cells. Nature 497, 619-623. (doi:10.1038/nature12148)
113. Rinaudo K, Bleris L, Maddamsetti R, Subramanian S, Weiss R, Benenson Y. 2007 A universal RNAi-based logic evaluator that operates in mammalian cells. Nat. Biotechnol. 25, 795-801. (doi:10.1038/nbt1307)
114. Auslander S, Auslander D, Muller M, Wieland M, Fussenegger M. 2012 Programmable single-cell mammalian biocomputers. Nature 487, 123-127.
115. Kramer BP, Fischer C, Fussenegger M. 2004 Biologic gates enable logical transcription control in mammalian cells. Biotechnol. Bioeng. 87, 478-484. (doi:10.1002/bit.20142)
116. Weber W, Stelling J, Rimann M, Keller B, Daoud-El Baba M, Weber CC, Aubel D, Fussenegger M. 2007 A synthetic time-delay circuit in mammalian cells and mice. Proc. Natl Acad. Sci. USA 104, 2643-2648. (doi:10.1073/pnas.0606398104)
117. Greber D, Fussenegger M. 2010 An engineered mammalian band-pass network. Nucleic Acids Res. 38, e174. (doi:10.1093/nar/gkq671)
118. Kramer BP, Fussenegger M. 2005 Hysteresis in a synthetic mammalian gene network. Proc. Natl Acad. Sci. USA 102, 9517-9522. (doi:10.1073/pnas.0500345102)
119. Nissim L, Bar-Ziv RH. 2010 A tunable dual-promoter integrator for targeting of cancer cells. Mol. Syst. Biol. 6, 444. (doi:10.1038/msb.2010.99)
120. Lohmueller JJ, Armel TZ, Silver PA. 2012 A tunable zinc finger-based framework for Boolean logic computation in mammalian cells. Nucleic Acids Res. 40, 5180-5187. (doi:10.1093/nar/gks142)
121. Bhaya D, Davison M, Barrangou R. 2011 CRISPR - Cas systems in Bacteria and Archaea: versatile small RNAs for adaptive defense and regulation. Annu. Rev. Genet. 45, 273-297. (doi:10.1146/annurev-genet-110410-132430)
122. Westra ER, Buckling A, Fineran PC. 2014 CRISPR - Cas systems: beyond adaptive immunity. Nat. Rev. Microbiol. 12, 317-326. (doi:10.1038/nrmicro3241)
123. Cho SW, Kim S, Kim JM, Kim JS. 2013 Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat. Biotechnol. 31, 230-232. (doi:10.1038/nbt.2507)
124. Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM. 2013 RNA-guided human genome engineering via Cas9. Science 339, 823-826. (doi:10.1126/science.1232033)
125. Cong L et al. 2013 Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819-823. (doi:10.1126/science.1231143)
126. Qi LS, Larson MH, Gilbert LA, Doudna JA, Weissman JS, Arkin AP, Lim WA. 2013 Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell 152, 1173-1183. (doi:10.1016/j.cell.2013.02.022)
127. Jinek M, Charpentier E, Chylinski K, Doudna CJH, Lim W, Qi L. 2013 Methods and compositions for RNA-directed target DNA modification and for RNA-directed modulation of transcription. U.S. Patent 20140068797 A1, March 6, 2014.
128. Farzadfard F, Perli SD, Lu TK. 2013 Tunable and multifunctional eukaryotic transcription factors based on CRISPR/CAS. ACS Synth. Biol. 2, 604-613. (doi:10.1021/sb400081r)
129. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. 2012 A programmable dual-RNA - guided DNA endonuclease in adaptive bacterial immunity. Science 337, 816-821. (doi:10.1126/science.1225829)
130. Maeder ML, Linder SJ, Cascio VM, Fu Y, Ho QH, Joung JK. 2013 CRISPR RNA-guided activation of endogenous human genes. Nat. Methods 10, 977-979. (doi:10.1038/nmeth.2598)
131. Perez-Pinera P et al. 2013 RNA-guided gene activation by CRISPR-CAS9-based transcription factors. Nat. Methods 10, 973-976. (doi:10.1038/nmeth.2600)
132. Kiani S, Beal J, Ebrahimkhani MR, Huh J, Hall RN, Xie Z, Li Y, Weiss R. 2014 CRISPR transcriptional repression devices and layered circuits in mammalian cells. Nat. Methods 11, 723-726. (doi:10.1038/nmeth.2969)
133. Nissim L, Perli SD, Fridkin A, Perez-Pinera P, Lu TK. 2014 Multiplexed and programmable regulation of gene networks with an integrated RNA and CRISPR/CAS toolkit in human cells. Mol. Cell 54, 698-710. (doi:10.1016/j.molcel.2014.04.022)
134. Kramer BP, Viretta AU, Daoud-El-Baba M, Aubel D, Weber W, Fussenegger M. 2004 An engineered epigenetic transgene switch in mammalian cells. Nat. Biotechnol. 22, 867-870. (doi:10.1038/nbt980)
135. Greber D, El-Baba MD, Fussenegger M. 2008 Intronically encoded siRNAs improve dynamic range of mammalian gene regulation systems and toggle switch. Nucleic Acids Res. 36, e101. (doi:10.1093/nar/gkn443)
136. Gillette MU, Sejnowski TJ. 2005 Physiology: biological clocks coordinately keep life on time. Science 309, 1196-1198. (doi:10.1126/science.1111420)
137. Schibler U, Sassone-Corsi P. 2002 A web of circadian pacemakers. Cell 111, 919-922. (doi:10.1016/S0092-8674(02)01225-4)
138. Kaasik K, Lee CC. 2004 Reciprocal regulation of haem biosynthesis and the circadian clock in mammals. Nature 430, 467-471. (doi:10.1038/nature02724)
139. Lahav G. 2004 The strength of indecisiveness: oscillatory behavior for better cell fate determination. Sci. STKE 2004, pe55.
140. Covert MW, Leung TH, Gaston JE, Baltimore D. 2005 Achieving stability of lipopolysaccharide-induced NF-kappa B activation. Science 309, 1854-1857. (doi:10.1126/science.1112304)
141. Tigges M, Marquez-Lago TT, Stelling J, Fussenegger M. 2009 A tunable synthetic mammalian oscillator. Nature 457, 309-312. (doi:10.1038/nature07616)
142. Tigges M, Denervaud N, Greber D, Stelling J, Fussenegger M. 2010 A synthetic low-frequency mammalian oscillator. Nucleic Acids Res. 38, 2702-2711. (doi:10.1093/nar/gkq121)
143. Mather W, Bennett MR, Hasty J, Tsimring LS. 2009 Delay-induced degrade-and-fire oscillations in small genetic circuits. Phys. Rev. Lett. 102, 068105. (doi:10.1103/PhysRevLett.102.068105)
144. Purcell O, Savery NJ, Grierson CS, di Bernardo M. 2010 A comparative analysis of synthetic genetic oscillators. J. R. Soc. Interface R. Soc. 7, 1503-1524. (doi:10.1098/rsif.2010.0183)
145. Stricker J, Cookson S, Bennett MR, Mather WH, Tsimring LS, Hasty J. 2008 A fast, robust and tunable synthetic gene oscillator. Nature 456, 516-519. (doi:10.1038/nature07389)
146. IOM (Institute of Medicine). 2011 The science and applications of synthetic and systems biology. Washington, DC: The National Academies Press.
147. Burrill DR, Inniss MC, Boyle PM, Silver PA. 2012 Synthetic memory circuits for tracking human cell fate. Genes Dev. 26, 1486-1497. (doi:10.1101/gad.189035.112)
148. Xie Z, Wroblewska L, Prochazka L, Weiss R, Benenson Y. 2011 Multi-input RNAi-based logic circuit for identification of specific cancer cells. Science 333, 1307-1311. (doi:10.1126/science.1205527)
149. O'Shaughnessy EC, Palani S, Collins JJ, Sarkar CA. 2011 Tunable signal processing in synthetic map kinase cascades. Cell 144, 119-131. (doi:10.1016/j.cell.2010.12.014)
150. Bardwell L. 2011 Synthetic biology: modulating the map kinase module. Curr. Biol. 21, R249-R251. (doi:10.1016/j.cub.2011.02.042)
151. Ye H, Daoud-El Baba M, Peng RW, Fussenegger MA. 2011 Synthetic optogenetic transcription device enhances blood-glucose homeostasis in mice. Science 332, 1565-1568. (doi:10.1126/science.1203535)
152. Stanley SA, Gagner JE, Damanpour S, Yoshida M, Dordick JS, Friedman JM. 2012 Radio-wave heating of iron oxide nanoparticles can regulate plasma glucose in mice. Science 336, 604-608. (doi:10.1126/science.1216753)
153. Ye H, Aubel D, Fussenegger M. 2013 Synthetic mammalian gene circuits for biomedical applications. Curr. Opin. Chem. Biol. 17, 910-917. (doi:10.1016/j.cbpa.2013.10.006)
154. Grupp SA et al. 2013 Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N. Engl. J. Med. 368, 1509-1518. (doi:10.1056/NEJMoa1215134)
155. Ye HF, Charpin-El Hamri G, Zwicky K, Christen M, Folcher M, Fussenegger M. 2013 Pharmaceutically controlled designer circuit for the treatment of the metabolic syndrome. Proc. Natl Acad. Sci. USA 110, 141-146. (doi:10.1073/pnas.1216801110)
156. Citorik RJ, Mimee M, Lu TK. 2014 Bacteriophage-based synthetic biology for the study of infectious diseases. Curr. Opin. Microbiol. 19C, 59-69. (doi:10.1016/j.mib.2014.05.022)
157. Yacoby I, Shamis M, Bar H, Shabat D, Benhar I. 2006 Targeting antibacterial agents by using drugcarrying filamentous bacteriophages. Antimicrob. Agents Chemother. 50, 2087-2097. (doi:10.1128/AAC.00169-06)
158. Jacobsson K, Frykberg L. 1996 Phage display shotgun cloning of ligand-binding domains of prokaryotic receptors approaches 100% correct clones. BioTechniques 20, 1070-1081.
159. Jönsson K, Guo BP, Monstein HJ, Mekalanos JJ, Kronvall G. 2004 Molecular cloning and characterization of two Helicobacter pylori genes coding for plasminogen-binding proteins. Proc. Natl Acad. Sci. USA 101, 1852-1857.
160. Temme K et al. 2012 Modular control of multiple pathways using engineered orthogonal T7 polymerases. Nucleic Acids Res. 40, 8773-8781. (doi:10.1093/nar/gks597)
161. Noireaux V, Bar-Ziv R, Libchaber A. 2003 Principles of cell-free genetic circuit assembly. Proc. Natl Acad. Sci. USA 100, 12 672-12 677.
162. Kim J, White KS, Winfree E. 2006 Construction of an in vitro bistable circuit from synthetic transcriptional switches. Mol. Syst. Biol. 2, 68. (doi:10.1038/msb4100099)
163. Friedland AE, Lu TK, Wang X, Shi D, Church G, Collins JJ. 2009 Synthetic gene networks that count. Science, 324, 1199-1202. (doi:10.1126/science.1172005)
164. Bonnet J, Yin P, Ortiz ME, Subsoontorn P, Endy D. 2013 Amplifying genetic logic gates. Science 340, 599-603. (doi:10.1126/science.1232758)
165. Datsenko KA, Wanner BL. 2000 One-step inactivation of chromosomal genes in Escherichia coli k-12 using PCR products. Proc. Natl Acad. Sci. USA 97, 6640-6645. (doi:10.1073/pnas.120163297)
166. Husseiny MI, Hensel M. 2005 Rapid method for the construction of Salmonella enterica serovar Typhimurium vaccine carrier strains. Infect. Immun. 73, 1598-1605. (doi:10.1128/IAI.73.3.1598-1605.2005)
167. Beloin C, Deighan P, Doyle M, Dorman CJ. 2003 Shigella flexneri 2a strain 2457T expresses three members of the H-NS-like protein family: characterization of the Sfh protein. Mol. Genet. Genomics 270, 66-77. (doi:10.1007/s00438-003-0897-0)
168. Yamamoto S, Izumiya H, Morita M, Arakawa E, Watanabe H. 2009 Application of λ Red recombination system to Vibrio cholerae genetics: simple methods for inactivation and modification of chromosomal genes. Gene 438, 57-64. (doi:10.1016/j.gene.2009.02.015)
169. Derbise A, Lesic B, Dacheux D, Ghigo JM, Carniel E. 2003 A rapid and simple method for inactivating chromosomal genes in Yersinia. FEMS Immunol. Med. Microbiol. 38, 113-116. (doi:10.1016/S0928-8244(03)00181-0)
170. Lesic B, Rahme LG. 2008 Use of the λ Red recombinase system to rapidly generate mutants in Pseudomonas aeruginosa. BMC Mol. Biol. 9, 20. (doi:10.1186/1471-2199-9-20)
171. Lu TK, Collins JJ. 2007 Dispersing biofilms with engineered enzymatic bacteriophage. Proc. Natl Acad. Sci. USA 104, 11 197-11 202. (doi:10.1073/pnas.0704624104)
172. Westwater C, Kasman LM, Schofield DA, Werner PA, Dolan JW, Schmidt MG, Norris JS. 2003 Use of genetically engineered phage to deliver antimicrobial agents to bacteria: an alternative therapy for treatment of bacterial infections. Antimicrob. Agents Chemother. 47, 1301-1307. (doi:10.1128/AAC.47.4.1301-1307.2003)
173. Edgar R, Friedman N, Molshanski-Mor S, Qimron U. 2012 Reversing bacterial resistance to antibiotics by phage-mediated delivery of dominant sensitive genes. Appl. Environ. Microbiol. 78, 744-751. (doi:10.1128/AEM.05741-11)
174. Schmidt M, Ganguli-Mitra A, Torgersen H, Kelle A, Deplazes A, Biller-Andorno N. 2009 A priority paper for the societal and ethical aspects of synthetic biology. Syst. Synth. Biol. 3, 3-7. (doi:10.1007/s11693-009-9034-7)
175. Bedau MA, Parke EC, Tangen U, Hantsche-Tangen B. 2009 Social and ethical checkpoints for bottom-up synthetic biology, or protocells. Syst. Synth. Biol. 3, 65-75. (doi:10.1007/s11693-009-9039-2)
176. Rabinow P, Bennett G. 2009 Synthetic biology: ethical ramifications 2009. Syst. Synth. Biol. 3, 99-108. (doi:10.1007/s11693-009-9042-7)
177. Aubel D, Morris R, Lennon B, Rimann M, Kaufmann H, Folcher M, Bailey JE, Thompson CJ, Fussenegger M. 2001 Design of a novel mammalian screening system for the detection of bioavailable, non-cytotoxic streptogramin antibiotics. J. Antibiot. 54, 44-55. (doi:10.7164/antibiotics.54.44)
178. Baulard AR, Betts JC, Engohang-Ndong J, Quan S, McAdam RA, Brennan PJ, Locht C, Besra GS. 2000 Activation of the pro-drug ethionamide is regulated in mycobacteria. J. Biol. Chem. 275, 28 326-28 331.
179. Gonzalez-Nicolini V, Fux C, Fussenegger M. 2004 A novel mammalian cell-based approach for the discovery of anticancer drugs with reduced cytotoxicity on non-dividing cells. Invest. New Drugs 22, 253-262. (doi:10.1023/B:DRUG.0000026251.00854.77)
180. Gonzalez-Nicolini V, Fussenegger M. 2005 In vitro assays for anticancer drug discovery: a novel approach based on engineered mammalian cell lines. Anticancer Drugs 16, 223-228. (doi:10.1097/00001813-200503000-00001)
181. Filmore D. 2004 It's a GPCR world. Cell-based screening assays and structural studies are fueling G-protein coupled receptors as one of the most popular classes of investigational drug targets. Mod. Drug Discov. 7, 24-28.
182. Xiao X, Min JL, Wang P, Chou KC. 2013 Predict drug - protein interaction in cellular networking. Curr. Top. Med. Chem. 13, 1707-1712. (doi:10.2174/15680266113139990121)
183. Esbenshade TA. 2005 G protein-coupled receptors as targets for drug discovery. In G protein-coupled receptors in drug discovery (eds KH Lundstrom, ML Chiu). Boca Raton, FL: Taylor and Francis.
184. PerkinElmer Inc. Receptor activation. See http://www.perkinelmer.co.uk/pages/020/cellularimaging/assays/receptoractivation.xhtml (accessed 16 March 2015).
185. Barnea G, Strapps W, Herrada G, Berman Y, Ong J, Kloss B, Axel R, Lee KJ. 2008 The genetic design of signaling cascades to record receptor activation. Proc. Natl Acad. Sci. USA 105, 64-69. (doi:10.1073/pnas.0710487105)
186. Seifert R, Wenzel-Seifert K, Kobilka BK. 1999 GPCR-G alpha fusion proteins: molecular analysis of receptor - G-protein coupling. Trends Pharmacol. Sci. 20, 383-389. (doi:10.1016/S0165-6147(99) 01368-1)
187. Li F, Vijayasankaran N, Shen AY, Kiss R, Amanullah A. 2010 Cell culture processes for monoclonal antibody production. mAbs 2, 466-479. (doi:10.4161/mabs.2.5.12720)
188. Marx U et al. 1997 Monoclonal antibody production - the report and recommendations of ECVAM workshop 23. Atla-Altern. Lab. Anim. 25, 121-137.
189. McLeod J, James DC. 2011 Engineering protein folding and secretion in eukaryotic cell factories. In Comprehensive biotechnology (ed. M Moo-Young). Amsterdam, The Netherlands: Elsevier Science and Technology Books.
190. Dinnis DM, James DC. 2005 Engineering mammalian cell factories for improved recombinant monoclonal antibody production: lessons from nature? Biotechnol. Bioeng. 91, 180-189. (doi:10.1002/bit.20499)