Cellular heterogeneity mediates inherent sensitivity-specificity tradeoff in cancer targeting by Synthetic circuits

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 29, 2016, Pages 8133-8138

  Morel, Mathieu ^a,b,c   Shtrahman, Roman ^a   Rotter, Varda ^a   Nissim, Lior ^d   Bar Ziv, Roy H ^a  

^a WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^b ECOLE NORMALE SUPÉRIEURE   (France)

^c SORBONNE UNIVERSITÉ   (France)

^d Massachusetts Institute of Technology   (United States)

Author keywords

Cancer gene therapy; Cell state targeting; Cellular heterogeneity; Mammalian synthetic biology; Synthetic gene circuits

Indexed keywords

SYNTHETIC DNA; CCND1 PROTEIN, HUMAN; CYCLIN D1; HISTONE; REPRESSOR PROTEIN; SYNOVIAL SARCOMA X BREAKPOINT PROTEINS; TUMOR PROTEIN;

CANCER CELL LINE; CELL HETEROGENEITY; CELL POPULATION; COLORECTAL CANCER; CONFERENCE PAPER; GENE AMPLIFICATION; GENE EXPRESSION; HUMAN; HUMAN CELL; NEOPLASM; PRIORITY JOURNAL; PROMOTER REGION; SENSITIVITY AND SPECIFICITY; SINGLE CELL ANALYSIS; CELL DEATH; CELL LINE; FIBROBLAST; GENE REGULATORY NETWORK; GENETICS; HCT 116 CELL LINE; SYNTHETIC BIOLOGY;

CELL DEATH; CELL LINE; CYCLIN D1; FIBROBLASTS; GENE REGULATORY NETWORKS; HCT116 CELLS; HISTONES; HUMANS; NEOPLASM PROTEINS; NEOPLASMS; PROMOTER REGIONS, GENETIC; REPRESSOR PROTEINS; SENSITIVITY AND SPECIFICITY; SYNTHETIC BIOLOGY;

EID: 84978886093     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1604391113     Document Type: Article

References (41)

1. Weber W, Fussenegger M (2011) Emerging biomedical applications of synthetic biology. Nat Rev Genet 13(1):21-35.
2. Bacchus W, Aubel D, Fussenegger M (2013) Biomedically relevant circuit-design strategies in mammalian synthetic biology. Mol Syst Biol 9(691):691.
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(2):95-107.
4. Russell SJ, Peng K-W, Bell JC (2012) Oncolytic virotherapy. Nat Biotechnol 30(7):658-670.
5. Srivastava S, Riddell SR (2015) Engineering CAR-T cells: Design concepts. Trends Immunol 36(8):494-502.
6. Robson T, Hirst DG (2003) Transcriptional targeting in cancer gene therapy. J Biomed Biotechnol 2003(2):110-137.
7. Anderson JC, Voigt CA, Arkin AP (2007) Environmental signal integration by a modular AND gate. Mol Syst Biol 3(133):133.
8. Nissim L, Beatus T, Bar-Ziv R (2007) An autonomous system for identifying and governing a cell's state in yeast. Phys Biol 4(3):154-163.
9. Tamsir A, Tabor JJ, Voigt CA (2011) Robust multicellular computing using genetically encoded NOR gates and chemical 'wires'. Nature 469(7329):212-215.
10. Ausländer S, Ausländer D, Müller M, Wieland M, Fussenegger M (2012) Programmable single-cell mammalian biocomputers. Nature 487(7405):123-127.
11. Lohmueller JJ, Armel TZ, Silver PA (2012) A tunable zinc finger-based framework for Boolean logic computation in mammalian cells. Nucleic Acids Res 40(11):5180-5187.
12. Moon TS, Lou C, Tamsir A, Stanton BC, Voigt CA (2012) Genetic programs constructed from layered logic gates in single cells. Nature 491(7423):249-253.
13. Bonnet J, Yin P, Ortiz ME, Subsoontorn P, Endy D (2013) Amplifying genetic logic gates. Science 340(6132):599-603.
14. Gaber R, et al. (2014) Designable DNA-binding domains enable construction of logic circuits in mammalian cells. Nat Chem Biol 10(3):203-208.
15. Khalil AS, et al. (2012) A synthetic biology framework for programming eukaryotic transcription functions. Cell 150(3):647-658.
16. Ang J, Harris E, Hussey BJ, Kil R, McMillen DR (2013) Tuning response curves for synthetic biology. ACS Synth Biol 2(10):547-567.
17. Nissim L, Bar-Ziv RH (2010) A tunable dual-promoter integrator for targeting of cancer cells. Mol Syst Biol 6(444):444.
18. 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(6047):1307-1311.
19. Levens D, Gupta A (2010) Reliable noise. Science 327(5969):1088-1089.
20. Eldar A, Elowitz MB (2010) Functional roles for noise in genetic circuits. Nature 467(7312):167-173.
21. Meacham CE, Morrison SJ (2013) Tumour heterogeneity and cancer cell plasticity. Nature 501(7467):328-337.
22. Daniel R, Rubens JR, Sarpeshkar R, Lu TK (2013) Synthetic analog computation in living cells. Nature 497(7451):619-623.
23. Barak Y, et al. (2005) Matching fusion protein systems for affinity analysis of two interacting families of proteins: The cohesin-dockerin interaction. J Mol Recognit 18(6):491-501.
24. Karpol A, Barak Y, Lamed R, Shoham Y, Bayer EA (2008) Functional asymmetry in cohesin binding belies inherent symmetry of the dockerin module: Insight into cellulosome assembly revealed by systematic mutagenesis. Biochem J 410(2):331-338.
25. Kim JH, et al. (2011) High cleavage efficiency of a 2A peptide derived from porcine teschovirus-1 in human cell lines, zebrafish and mice. PLoS One 6(4):e18556.
26. Milyavsky M, et al. (2003) Prolonged culture of telomerase-immortalized human fibroblasts leads to a premalignant phenotype. Cancer Res 63(21):7147-7157.
27. Milyavsky M, et al. (2005) Transcriptional programs following genetic alterations in p53, INK4A, and H-Ras genes along defined stages of malignant transformation. Cancer Res 65(11):4530-4543.
28. Buganim Y, et al. (2010) p53 Regulates the Ras circuit to inhibit the expression of a cancer-related gene signature by various molecular pathways. Cancer Res 70(6):2274-2284.
29. Dull T, et al. (1998) A third-generation lentivirus vector with a conditional packaging system. J Virol 72(11):8463-8471.
30. Hanley JA, McNeil BJ (1982) The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143(1):29-36.
31. Rubsam LZ, Boucher PD, Murphy PJ, Ku Kuruga M, Shewach DS (1999) Cytotoxicity and accumulation of ganciclovir triphosphate in bystander cells cocultured with herpes simplex virus type 1 thymidine kinase-expressing human glioblastoma cells. Cancer Res 59(3):669-675.
32. Zomer A, et al. (2015) In vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior. Cell 161(5):1046-1057.
33. Kelm JM, Timmins NE, Brown CJ, Fussenegger M, Nielsen LK (2003) Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types. Biotechnol Bioeng 83(2):173-180.
34. Nyga A, Cheema U, Loizidou M (2011) 3D tumour models: Novel in vitro approaches to cancer studies. J Cell Commun Signal 5(3):239-248.
35. Tanner K, Gottesman MM (2015) Beyond 3D culture models of cancer. Sci Transl Med 7(283):283ps9.
36. Costello JC, et al.; NCI DREAM Community (2014) A community effort to assess and improve drug sensitivity prediction algorithms. Nat Biotechnol 32(12):1202-1212.
37. Conde J, Oliva N, Atilano M, Song HS, Artzi N (2016) Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment. Nat Mater 15(3):353-363.
38. Wilkie S, et al. (2012) Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling. J Clin Immunol 32(5):1059-1070.
39. Kloss CC, Condomines M, Cartellieri M, Bachmann M, Sadelain M (2013) Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Nat Biotechnol 31(1):71-75.
40. Roybal KT, et al. (2016) Precision tumor recognition by T cells with combinatorial antigen-sensing circuits. Cell 164(4):770-779.
41. van't Veer LJ, Bernards R (2008) Enabling personalized cancer medicine through analysis of gene-expression patterns. Nature 452(7187):564-570.