Abstract
Synthetic biology breakthroughs have facilitated genetic circuit engineering to program cells through novel biological functions, dynamic gene expressions, as well as logic controls. SynBio can also participate in the rapid development of new treatments required for the human lifestyle. Moreover, these technologies are applied in the development of innovative therapeutic, diagnostic, as well as discovery-related methods within a wide range of cellular and molecular applications. In the present review study, SynBio applications in various cellular and molecular fields such as novel strategies for cancer therapy, biosensing, metabolic engineering, protein engineering, and tissue engineering were highlighted and summarized. The major safety and regulatory concerns about synthetic biology will be the environmental release, legal concerns, and risks of the engineered organisms. The final sections focused on limitations to SynBio.
Similar content being viewed by others
References
Nandagopal N, Elowitz MB (2011) Synthetic biology: integrated gene circuits. Science 333(6047):1244–1248
Schmidt M (2012) Synthetic biology: industrial and environmental applications. Wiley, Weinheim
Gruber AR, Lorenz R, Bernhart SH, Neuböck R, Hofacker IL (2008) The vienna RNA websuite. Nucleic Acids Res 36(suppl_2):W70–W74
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(6096):816–821
MacDonald IC, Deans TL (2016) Tools and applications in synthetic biology. Adv Drug Deliv Rev 105:20–34
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
Rodrigues LR, Kluskens LD (2011) Synthetic biology & bioinformatics: prospects in the cancer arena. Comput Biol Appl Bioinform 8:159–186
Shiue E, Prather KL (2012) Synthetic biology devices as tools for metabolic engineering. Biochem Eng J 65:82–89
Chen YY, Galloway KE, Smolke CD (2012) Synthetic biology: advancing biological frontiers by building synthetic systems. Genome Biol 13(2):240
Hermsen R, Tans S, Ten Wolde PR (2006) Transcriptional regulation by competing transcription factor modules. PLoS Comput Biol 2(12):e164
Singh V (2014) Recent advances and opportunities in synthetic logic gates engineering in living cells. Syst Synth Biol 8(4):271–282
Trump BD (2017) Synthetic biology regulation and governance: lessons from TAPIC for the United States, European Union, and Singapore. Health Policy 121(11):1139–1146
Dobrin A, Saxena P, Fussenegger M (2015) Synthetic biology: applying biological circuits beyond novel therapies. Integr Biol 8(4):409–430
Dalchau N, Smith MJ, Martin S, Brown JR, Emmott S, Phillips A (2012) Towards the rational design of synthetic cells with prescribed population dynamics. J R Soc Interface 9(76):2883–2898
Brenner MJ, Cho JH, Wong NM, Wong WW (2018) Synthetic biology: immunotherapy by design. Annu Rev Biomed Eng 20:95–118
DuPage M, Mazumdar C, Schmidt LM, Cheung AF, Jacks T (2012) Expression of tumour-specific antigens underlies cancer immunoediting. Nature 482(7385):405
Shiao SL, Ganesan AP, Rugo HS, Coussens LM (2011) Immune microenvironments in solid tumors: new targets for therapy. Genes Dev 25(24):2559–2572
Chakravarti D, Wong WW (2015) Synthetic biology in cell-based cancer immunotherapy. Trends Biotechnol 33(8):449–461
Kershaw MH, Westwood JA, Parker LL, Wang G, Eshhar Z, Mavroukakis SA et al (2006) A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res 12(20):6106–6115
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
Kudo K, Imai C, Lorenzini P, Kamiya T, Kono K, Davidoff AM et al (2014) T lymphocytes expressing a CD16 signaling receptor exert antibody-dependent cancer cell killing. Can Res 74(1):93–103
Kojima R, Scheller L, Fussenegger M (2018) Nonimmune cells equipped with T-cell-receptor-like signaling for cancer cell ablation. Nat Chem Biol 14(1):42
Gaj T, Gersbach CA, Barbas CF III (2013) ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol 31(7):397–405
Tastanova A, Folcher M, Müller M, Camenisch G, Ponti A, Horn T et al (2018) Synthetic biology-based cellular biomedical tattoo for detection of hypercalcemia associated with cancer. Scie Transl Med 10(437):eaap8562
Chen Z, He A, Liu Y, Huang W, Cai Z (2016) Recent development on synthetic biological devices treating bladder cancer. Synth Syst Biotechnol 1(4):216–220
Foo JL, Ching CB, Chang MW, Leong SSJ (2012) The imminent role of protein engineering in synthetic biology. Biotechnol Adv 30(3):541–549
Ying B-W, Taguchi H, Kondo M, Ueda T (2005) Co-translational involvement of the chaperonin GroEL in the folding of newly translated polypeptides. J Biol Chem 280(12):12035–12040
Kerner MJ, Naylor DJ, Ishihama Y, Maier T, Chang H-C, Stines AP et al (2005) Proteome-wide analysis of chaperonin-dependent protein folding in Escherichia coli. Cell 122(2):209–220
Wang JD, Herman C, Tipton KA, Gross CA, Weissman JS (2002) Directed evolution of substrate-optimized GroEL/S chaperonins. Cell 111(7):1027–1039
Kumar V, Punetha A, Sundar D, Chaudhuri TK (2012) In silico engineering of aggregation-prone recombinant proteins for substrate recognition by the chaperonin GroEL. BMC genomics. BioMed Central, London
Gainza-Cirauqui P, Correia BE (2018) Computational protein design—the next generation tool to expand synthetic biology applications. Curr Opin Biotechnol 52:145–152
Liu DS, Nivón LG, Richter F, Goldman PJ, Deerinck TJ, Yao JZ et al (2014) Computational design of a red fluorophore ligase for site-specific protein labeling in living cells. Proc Natl Acad Sci 111(43):E4551–E4559
Reeve SM, Gainza P, Frey KM, Georgiev I, Donald BR, Anderson AC (2015) Protein design algorithms predict viable resistance to an experimental antifolate. Proc Natl Acad Sci 112(3):749–754
Erb TJ, Jones PR, Bar-Even A (2017) Synthetic metabolism: metabolic engineering meets enzyme design. Curr Opin Chem Biol 37:56–62
Keasling JD (2012) Synthetic biology and the development of tools for metabolic engineering. Metab Eng 14(3):189–195
Brekasis D, Paget MS (2003) A novel sensor of NADH/NAD+ redox poise in Streptomyces coelicolor A3 (2). EMBO J 22(18):4856–4865
Weber W, Link N, Fussenegger M (2006) A genetic redox sensor for mammalian cells. Metab Eng 8(3):273–280
Levskaya A, Weiner OD, Lim WA, Voigt CA (2009) Spatiotemporal control of cell signalling using a light-switchable protein interaction. Nature 461(7266):997
Courbet A, Renard E, Molina F (2016) Bringing next-generation diagnostics to the clinic through synthetic biology. EMBO Mol Med 8(9):987–991
Bhatia P, Chugh A (2013) Synthetic biology based biosensors and the emerging governance issues. Curr Synthetic Syst Biol. https://doi.org/10.4172/2332-0737.1000108
Wei T, Zhang C, Xu X, Hanna M, Zhang X, Wang Y et al (2013) Construction and evaluation of two biosensors based on yeast transcriptional response to genotoxic chemicals. Biosens Bioelectron 44:138–145
Morris MC (2013) Fluorescent biosensors—probing protein kinase function in cancer and drug discovery. Biochimica et Biophysica Acta (BBA) 1834(7):1387–1395
Braff D, Shis D, Collins JJ (2016) Synthetic biology platform technologies for antimicrobial applications. Adv Drug Deliv Rev 105:35–43
Slomovic S, Pardee K, Collins JJ (2015) Synthetic biology devices for in vitro and in vivo diagnostics. Proc Natl Acad Sci 112(47):14429–14435
Carlson ED, Gan R, Hodgman CE, Jewett MC (2012) Cell-free protein synthesis: applications come of age. Biotechnol Adv 30(5):1185–1194
Endo Y, Sawasaki T (2006) Cell-free expression systems for eukaryotic protein production. Curr Opin Biotechnol 17(4):373–380
Smith MT, Wilding KM, Hunt JM, Bennett AM, Bundy BC (2014) The emerging age of cell-free synthetic biology. FEBS Lett 588(17):2755–2761
Sun ZZ, Hayes CA, Shin J, Caschera F, Murray RM, Noireaux V (2013) Protocols for implementing an Escherichia coli based TX-TL cell-free expression system for synthetic biology. JoVE 79:e50762
Sun ZZ, Yeung E, Hayes CA, Noireaux V, Murray RM (2013) Linear DNA for rapid prototyping of synthetic biological circuits in an Escherichia coli based TX-TL cell-free system. ACS Synth Biol 3(6):387–397
Pardee K, Green AA, Ferrante T, Cameron DE, DaleyKeyser A, Yin P et al (2014) Based synthetic gene networks. Cell 159(4):940–954
Carroll MW, Matthews DA, Hiscox JA, Elmore MJ, Pollakis G, Rambaut A et al (2015) Temporal and spatial analysis of the 2014–2015 Ebola virus outbreak in West Africa. Nature 524(7563):97
Green AA, Silver PA, Collins JJ, Yin P (2014) Toehold switches: de-novo-designed regulators of gene expression. Cell 159(4):925–939
Evans A, Ratcliffe E (2017) Rising influence of synthetic biology in regenerative medicine. Eng Biol 1(1):24–29
Davies JA, Cachat E (2016) Synthetic biology meets tissue engineering. Biochem Soc Trans 44(3):696–701
Ye H, Daoud-El Baba M, Peng R-W, Fussenegger M (2011) A synthetic optogenetic transcription device enhances blood-glucose homeostasis in mice. Science 332(6037):1565–1568
Gelain F, Horii A, Zhang S (2007) Designer self-assembling peptide scaffolds for 3-D tissue cell cultures and regenerative medicine. Macromol Biosci 7(5):544–551
Papapostolou D, Howorka S (2009) Engineering and exploiting protein assemblies in synthetic biology. Mol BioSyst 5(7):723–732
Cachat E, Davies J (2011) Application of synthetic biology to regenerative medicine. J Bioeng Biomed Sci 2:003
Davies J (2013) Mechanisms of morphogenesis. Academic Press, New York
Davies JA (2008) Synthetic morphology: prospects for engineered, self-constructing anatomies. J Anat 212(6):707–719
Zalatan JG, Lee ME, Almeida R, Gilbert LA, Whitehead EH, La Russa M et al (2015) Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds. Cell 160(1–2):339–350
Purnick PE, Weiss R (2009) The second wave of synthetic biology: from modules to systems. Nat Rev Mol Cell Biol 10(6):410
Jagadevan S, Banerjee A, Banerjee C, Guria C, Tiwari R, Baweja M et al (2018) Recent developments in synthetic biology and metabolic engineering in microalgae towards biofuel production. Biotechnol Biofuels 11(1):185
Kindsmüller K, Wagner R (2011) Synthetic biology: impact on the design of innovative vaccines. Hum Vaccines 7(6):658–662
Jain A, Bhatia P, Chugh A (2012) Microbial synthetic biology for human therapeutics. Syst Synth Biol 6(1–2):9–22
Trump BD, Cegan JC, Wells E, Keisler J, Linkov I (2018) A critical juncture for synthetic biology. EMBO Rep 19(7):e46153
Zakeri B, Carr PA (2015) The limits of synthetic biology. Trends Biotechnol 33(2):57–58
Serrano L (2007) Synthetic biology: promises and challenges. Mol Syst Biol 3(1):158
Bhutkar A (2005) Synthetic biology: navigating the challenges ahead. J Biolaw Bus 8(2):19–29
Epstein MM, Vermeire T (2016) Scientific opinion on risk assessment of synthetic biology. Trends Biotechnol 34(8):601–603
Wang F, Zhang W (2019) Synthetic biology: recent progress, biosafety and biosecurity concerns, and possible solutions. J Biosaf Biosecur. https://doi.org/10.1016/j.jobb.2018.12.003
Ehni H-J (2008) Dual use and the ethical responsibility of scientists. Arch Immunol Ther Exp 56(3):147
Kuhlau F, Eriksson S, Evers K, Höglund AT (2008) Taking due care: moral obligations in dual use research. Bioethics 22(9):477–487
Nordmann BD (2010) Issues in biosecurity and biosafety. Int J Antimicrob Agents 36:S66–S69
Funding
None.
Author information
Authors and Affiliations
Contributions
All authors collected and analyzed relevant literature, then drafted the manuscript, and critically revised the manuscript for content, finally read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflicts of interest
The authors report that there are no conflicts of interest.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Safaei, M., Mobini, GR., Abiri, A. et al. Synthetic biology in various cellular and molecular fields: applications, limitations, and perspective. Mol Biol Rep 47, 6207–6216 (2020). https://doi.org/10.1007/s11033-020-05565-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-020-05565-6