Next-generation biocontainment systems for engineered organisms

Next-generation biocontainment systems for engineered organisms

Play all audios:

Loading...

ABSTRACT The increasing use of engineered organisms for industrial, clinical, and environmental applications poses a growing risk of spreading hazardous biological entities into the


environment. To address this biosafety issue, significant effort has been invested in creating ways to confine these organisms and transgenic materials. Emerging technologies in synthetic


biology involving genetic circuit engineering, genome editing, and gene expression regulation have led to the development of novel biocontainment systems. In this perspective, we highlight


recent advances in biocontainment and suggest a number of approaches for future development, which may be applied to overcome remaining challenges in safeguard implementation. Access through


your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Access Nature and 54 other Nature


Portfolio journals Get Nature+, our best-value online-access subscription $29.99 / 30 days cancel any time Learn more Subscribe to this journal Receive 12 print issues and online access


$259.00 per year only $21.58 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are


calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS


CELL-FREE GENE EXPRESSION Article 15 July 2021 AN ENDORIBONUCLEASE-BASED FEEDFORWARD CONTROLLER FOR DECOUPLING RESOURCE-LIMITED GENETIC MODULES IN MAMMALIAN CELLS Article Open access 10


November 2020 CAS9-ASSISTED BIOLOGICAL CONTAINMENT OF A GENETICALLY ENGINEERED HUMAN COMMENSAL BACTERIUM AND GENETIC ELEMENTS Article Open access 07 March 2024 REFERENCES * Khalil, A. S.


& Collins, J. J. Synthetic biology: applications come of age. _Nat. Rev. Genet._ 11, 367–379 (2010). Article  CAS  PubMed  PubMed Central  Google Scholar  * Lee, J. W. et al. Systems


metabolic engineering of microorganisms for natural and non-natural chemicals. _Nat. Chem. Biol._ 8, 536–546 (2012). Article  CAS  PubMed  Google Scholar  * Cameron, D. E., Bashor, C. J.


& Collins, J. J. A brief history of synthetic biology. _Nat. Rev. Microbiol._ 12, 381–390 (2014). Article  CAS  PubMed  Google Scholar  * Berg, P., Baltimore, D., Brenner, S., Roblin, R.


O. & Singer, M. F. Summary statement of the Asilomar conference on recombinant DNA molecules. _Proc. Natl Acad. Sci. USA_ 72, 1981–1984 (1975). Article  CAS  PubMed  PubMed Central 


Google Scholar  * Berg, P., Baltimore, D., Brenner, S., Roblin, R. O. III & Singer, M. F. Asilomar conference on recombinant DNA molecules. _Science_ 188, 991–994 (1975). Article  CAS 


PubMed  Google Scholar  * Wilson, D. J. NIH guidelines for research involving recombinant DNA molecules. _Account. Res._ 3, 177–185 (1993). Article  PubMed  Google Scholar  * Sears, M. K. et


al. Impact of Bt corn pollen on monarch butterfly populations: a risk assessment. _Proc. Natl Acad. Sci. USA_ 98, 11937–11942 (2001). Article  CAS  PubMed  PubMed Central  Google Scholar  *


Stanley-Horn, D. E. et al. Assessing the impact of Cry1Ab-expressing corn pollen on monarch butterfly larvae in field studies. _Proc. Natl Acad. Sci. USA_ 98, 11931–11936 (2001). Article 


CAS  PubMed  PubMed Central  Google Scholar  * Snow, A. A. Transgenic crops why gene flow matters. _Nat. Biotechnol._ 20, 542 (2002). Article  CAS  PubMed  Google Scholar  * Giovannetti, M.


The ecological risks of transgenic plants. _Riv. Biol._ 96, 207–223 (2003). PubMed  Google Scholar  * Hills, M. J., Hall, L., Arnison, P. G. & Good, A. G. Genetic use restriction


technologies (GURTs): strategies to impede transgene movement. _Trends Plant Sci_. 12, 177–183 (2007). Article  CAS  PubMed  Google Scholar  * Quist, D. & Chapela, I. H. Transgenic DNA


introgressed into traditional maize landraces in Oaxaca, Mexico. _Nature_ 414, 541–543 (2001). Article  CAS  PubMed  Google Scholar  * Colomer-Lluch, M., Imamovic, L., Jofre, J. &


Muniesa, M. Bacteriophages carrying antibiotic resistance genes in fecal waste from cattle, pigs, and poultry. _Antimicrob. Agents Chemother._ 55, 4908–4911 (2011). Article  CAS  PubMed 


PubMed Central  Google Scholar  * Moe-Behrens, G. H., Davis, R. & Haynes, K. A. Preparing synthetic biology for the world. _Front. Microbiol._ 4, 5 (2013). THIS REVIEW PROVIDES A


DETAILED SUMMARY OF THE DEVELOPMENT OF PIONEERING BIOCONTAINMENT SYSTEMS. Article  PubMed  PubMed Central  Google Scholar  * Dana, G. V., Kuiken, T., Rejeski, D. & Snow, A. A. Synthetic


biology: four steps to avoid a synthetic-biology disaster. _Nature_ 483, 29 (2012). Article  CAS  PubMed  Google Scholar  * Wright, O., Stan, G. B. & Ellis, T. Building-in biosafety for


synthetic biology. _Microbiology_ 159, 1221–1235 (2013). Article  CAS  PubMed  Google Scholar  * Schmidt, M. & de Lorenzo, V. Synthetic bugs on the loose: containment options for deeply


engineered (micro)organisms. _Curr. Opin. Biotechnol._ 38, 90–96 (2016). Article  CAS  PubMed  Google Scholar  * Schmidt, M. & Pei, L. in _Hydrocarbon and Lipid Microbiology Protocols:


Synthetic and Systems Biology - Tools_ (eds. McGenity, T.J., Timmis, K.N. & Nogales, B.) 185–199 (Springer Berlin Heidelberg, Berlin, Heidelberg, 2016). * Oliver, M. J., Quisenberry, J.


E., Trolinder, N. L. G. & Keim, D. H. Control of plant gene expression. US Patent 5,723,765 (1998).  * Naldini, L. et al. In vivo gene delivery and stable transduction of nondividing


cells by a lentiviral vector. _Science_ 272, 263–267 (1996). Article  CAS  PubMed  Google Scholar  * Dull, T. et al. A third-generation lentivirus vector with a conditional packaging system.


_J. Virol._ 72, 8463–8471 (1998). CAS  PubMed  PubMed Central  Google Scholar  * Burns, J. C., Friedmann, T., Driever, W., Burrascano, M. & Yee, J. K. Vesicular stomatitis virus G


glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells. _Proc. Natl Acad. Sci. USA_ 90, 8033–8037


(1993). Article  CAS  PubMed  PubMed Central  Google Scholar  * Steidler, L. et al. Biological containment of genetically modified _Lactococcus lactis_ for intestinal delivery of human


interleukin 10. _Nat. Biotechnol._ 21, 785–789 (2003). THIS ARTICLE DESCRIBES ONE OF THE EARLIEST CLINICAL STUDIES INVOLVING A PROBIOTIC STRAIN EQUIPPED WITH A BIOCONTAINMENT SYSTEM. Article


  CAS  PubMed  Google Scholar  * Bahey-El-Din, M., Casey, P. G., Griffin, B. T. & Gahan, C. G. Efficacy of a _Lactococcus lactis_ ΔpyrG vaccine delivery platform expressing chromosomally


integrated hly from _Listeria monocytogenes_. _Bioeng. Bugs_ 1, 66–74 (2010). Article  PubMed  PubMed Central  Google Scholar  * Ronchel, M. C. & Ramos, J. L. Dual system to reinforce


biological containment of recombinant bacteria designed for rhizoremediation. _Appl. Environ. Microbiol._ 67, 2649–2656 (2001). Article  CAS  PubMed  PubMed Central  Google Scholar  *


Lajoie, M. J. et al. Genomically recoded organisms expand biological functions. _Science_ 342, 357–360 (2013). Article  CAS  PubMed  PubMed Central  Google Scholar  * Rovner, A. J. et al.


Recoded organisms engineered to depend on synthetic amino acids. _Nature_ 518, 89–93 (2015). THIS PAPER (ALONG WITH THE ONE IN REF. 28) PRESENTS THE DEVELOPMENT OF SYNTHETIC AUXOTROPH-BASED


BIOCONTAINMENT SYSTEMS REQUIRING AN UNNATURAL AMINO ACID FOR THE SYNTHESIS OF ESSENTIAL PROTEINS, IN TWO PARALLEL STUDIES. Article  CAS  PubMed  PubMed Central  Google Scholar  * Mandell, D.


J. et al. Biocontainment of genetically modified organisms by synthetic protein design. _Nature_ 518, 55–60 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Callura, J. M.,


Dwyer, D. J., Isaacs, F. J., Cantor, C. R. & Collins, J. J. Tracking, tuning, and terminating microbial physiology using synthetic riboregulators. _Proc. Natl Acad Sci. USA_ 107,


15898–15903 (2010). Article  PubMed  PubMed Central  Google Scholar  * Gallagher, R. R., Patel, J. R., Interiano, A. L., Rovner, A. J. & Isaacs, F. J. Multilayered genetic safeguards


limit growth of microorganisms to defined environments. _Nucleic Acids Res._ 43, 1945–1954 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Cai, Y. et al. Intrinsic


biocontainment: multiplex genome safeguards combine transcriptional and recombinational control of essential yeast genes. _Proc. Natl Acad. Sci. USA_ 112, 1803–1808 (2015). Article  CAS 


PubMed  PubMed Central  Google Scholar  * Agmon, N. et al. Low escape-rate genome safeguards with minimal molecular perturbation of_ Saccharomyces cerevisiae_. _Proc. Natl Acad. Sci. USA_


114, E1470–E1479 (2017). Article  CAS  PubMed  PubMed Central  Google Scholar  * Huang, S. et al. Coupling spatial segregation with synthetic circuits to control bacterial survival. _Mol.


Syst. Biol._ 12, 859 (2016). Article  PubMed  PubMed Central  Google Scholar  * Chan, C. T., Lee, J. W., Cameron, D. E., Bashor, C. J. & Collins, J. J. ‘Deadman’ and ‘Passcode’ microbial


kill switches for bacterial containment. _Nat. Chem. Biol._ 12, 82–86 (2016). THIS ARTICLE DESCRIBES ONE OF THE FIRST SAFEGUARD SYSTEMS DESIGNED TO PROVIDE PROGRAMMABLE CONDITIONS FOR


BIOCONTAINMENT. Article  CAS  PubMed  Google Scholar  * Molina, L., Ramos, C., Ronchel, M. C., Molin, S. & Ramos, J. L. Construction of an efficient biologically contained _pseudomonas


putida_ strain and its survival in outdoor assays. _Appl. Environ. Microbiol._ 64, 2072–2078 (1998). CAS  PubMed  PubMed Central  Google Scholar  * Contreras, A., Molin, S. & Ramos, J.


L. Conditional-suicide containment system for bacteria which mineralize aromatics. _Appl. Environ. Microbiol._ 57, 1504–1508 (1991). CAS  PubMed  PubMed Central  Google Scholar  * Weaver, K.


E. The par toxin-antitoxin system from _Enterococcus faecalis_ plasmid pAD1 and its chromosomal homologs. _RNA Biol._ 9, 1498–1503 (2012). Article  CAS  PubMed  PubMed Central  Google


Scholar  * Durand, S., Jahn, N., Condon, C. & Brantl, S. Type I toxin-antitoxin systems in _Bacillus subtilis_. _RNA Biol._ 9, 1491–1497 (2012). Article  CAS  PubMed  Google Scholar  *


Diago-Navarro, E. et al. parD toxin-antitoxin system of plasmid R1–basic contributions, biotechnological applications and relationships with closely-related toxin-antitoxin systems. _FEBS


J._ 277, 3097–3117 (2010). Article  CAS  PubMed  Google Scholar  * Yagura, M., Nishio, S. Y., Kurozumi, H., Wang, C. F. & Itoh, T. Anatomy of the replication origin of plasmid ColE2-P9.


_J. Bacteriol._ 188, 999–1010 (2006). Article  CAS  PubMed  PubMed Central  Google Scholar  * del Solar, G., Giraldo, R., Ruiz-Echevarría, M. J., Espinosa, M. & Díaz-Orejas, R.


Replication and control of circular bacterial plasmids. _Microbiol. Mol. Biol. Rev._ 62, 434–464 (1998). PubMed  PubMed Central  Google Scholar  * Caliando, B. J. & Voigt, C. A. Targeted


DNA degradation using a CRISPR device stably carried in the host genome. _Nat. Commun._ 6, 6989 (2015). Article  CAS  PubMed  Google Scholar  * Chavez, A. et al. Precise Cas9 targeting


enables genomic mutation prevention. _Proc. Natl Acad. Sci. USA_ https://doi.org/10.1073/pnas.1718148115 (2018). * Callaway, E. ‘Minimal’ cell raises stakes in race to harness synthetic


life. _Nature_ 531, 557–558 (2016). Article  CAS  PubMed  Google Scholar  * Johns, N. I., Blazejewski, T., Gomes, A. L. & Wang, H. H. Principles for designing synthetic microbial


communities. _Curr. Opin. Microbiol._ 31, 146–153 (2016). Article  PubMed  PubMed Central  Google Scholar  * Mee, M. T., Collins, J. J., Church, G. M. & Wang, H. H. Syntrophic exchange


in synthetic microbial communities. _Proc. Natl Acad. Sci. USA_ 111, E2149–E2156 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar  * Wang, K., Neumann, H., Peak-Chew, S. Y. &


Chin, J. W. Evolved orthogonal ribosomes enhance the efficiency of synthetic genetic code expansion. _Nat. Biotechnol._ 25, 770–777 (2007). Article  CAS  PubMed  Google Scholar  * Neumann,


H., Wang, K., Davis, L., Garcia-Alai, M. & Chin, J. W. Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome. _Nature_ 464, 441–444 (2010). Article  CAS


  PubMed  Google Scholar  * Terasaka, N., Hayashi, G., Katoh, T. & Suga, H. An orthogonal ribosome-tRNA pair via engineering of the peptidyl transferase center. _Nat. Chem. Biol._ 10,


555–557 (2014). Article  CAS  PubMed  Google Scholar  * Soye, B. J. D., Patel, J. R., Isaacs, F. J. & Jewett, M. C. Repurposing the translation apparatus for synthetic biology. _Curr.


Opin. Chem. Biol._ 28, 83–90 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Marlière, P. et al. Chemical evolution of a bacterium’s genome. _Angew. Chem. Int. Edn. Engl._


50, 7109–7114 (2011). THIS ARTICLE INVOLVED THE ENGINEERING OF A BACTERIAL STRAIN THAT IS CAPABLE OF USING 5-CHLOROURACIL TO REPLACE THYMINE IN DNA, WHICH IS ONE OF THE FIRST EXAMPLES OF A


XENOBIOLOGICAL SYSTEM. Article  CAS  Google Scholar  * Pinheiro, V. B. et al. Synthetic genetic polymers capable of heredity and evolution. _Science_ 336, 341–344 (2012). THIS PAPER PRESENTS


THE DEVELOPMENT OF XENOBIOLOGICAL SYSTEMS THAT REPLACE CANONICAL NUCLEOSIDES WITH DIFFERENT TYPES OF SYNTHETIC ANALOGS. Article  CAS  PubMed  PubMed Central  Google Scholar  * Malyshev, D.


A. et al. A semi-synthetic organism with an expanded genetic alphabet. _Nature_ 509, 385–388 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar  * Adamala, K. P., Martin-Alarcon,


D. A., Guthrie-Honea, K. R. & Boyden, E. S. Engineering genetic circuit interactions within and between synthetic minimal cells. _Nat. Chem._ 9, 431–439 (2017). THIS ARTICLE DESCRIBES


THE CAPABILITY OF A CELL-FREE SYSTEM TO REPLACE LIVING ENTITIES IN A RANGE OF APPLICATIONS IN BIOMEDICINE AND BIOTECHNOLOGY. Article  CAS  PubMed  Google Scholar  * Pardee, K. et al.


Paper-based synthetic gene networks. _Cell_ 159, 940–954 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar  * Pardee, K. et al. Rapid, low-cost detection of Zika virus using


programmable biomolecular components. _Cell_ 165, 1255–1266 (2016). Article  CAS  PubMed  Google Scholar  * Pardee, K. et al. Portable, on-demand biomolecular manufacturing. _Cell_ 167,


248–259.e12 (2016). Article  CAS  PubMed  Google Scholar  * Dudley, Q. M., Karim, A. S. & Jewett, M. C. Cell-free metabolic engineering: biomanufacturing beyond the cell. _Biotechnol.


J._ 10, 69–82 (2015). Article  CAS  PubMed  Google Scholar  * Garamella, J., Marshall, R., Rustad, M. & Noireaux, V. The All _E. coli_ TX-TL Toolbox 2.0: A platform for cell-free


synthetic biology. _ACS Synth. Biol._ 5, 344–355 (2016). Article  CAS  PubMed  Google Scholar  * Hong, S. H. et al. Cell-free protein synthesis from a release factor 1 deficient _Escherichia


coli_ activates efficient and multiple site-specific nonstandard amino acid incorporation. _ACS Synth. Biol._ 3, 398–409 (2014). Article  CAS  PubMed  Google Scholar  * Lu, T. K. &


Koeris, M. S. The next generation of bacteriophage therapy. _Curr. Opin. Microbiol._ 14, 524–531 (2011). Article  PubMed  Google Scholar  * Krom, R. J., Bhargava, P., Lobritz, M. A. &


Collins, J. J. Engineered phagemids for nonlytic, targeted antibacterial therapies. _Nano. Lett._ 15, 4808–4813 (2015). Article  CAS  PubMed  Google Scholar  * Bikard, D. et al. Exploiting


CRISPR-Cas nucleases to produce sequence-specific antimicrobials. _Nat. Biotechnol._ 32, 1146–1150 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar  * Citorik, R. J., Mimee, M.


& Lu, T. K. Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases. _Nat. Biotechnol._ 32, 1141–1145 (2014). Article  CAS  PubMed  PubMed Central  Google


Scholar  * Ando, H., Lemire, S., Pires, D. P. & Lu, T. K. Engineering modular viral scaffolds for targeted bacterial population editing. _Cell Syst_. 1, 187–196 (2015). Article  CAS 


PubMed  PubMed Central  Google Scholar  * Yosef, I., Manor, M., Kiro, R. & Qimron, U. Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria.


_Proc. Natl Acad. Sci. USA_ 112, 7267–7272 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Champer, J., Buchman, A. & Akbari, O. S. Cheating evolution: engineering gene


drives to manipulate the fate of wild populations. _Nat. Rev. Genet._ 17, 146–159 (2016). Article  CAS  PubMed  Google Scholar  * DiCarlo, J. E., Chavez, A., Dietz, S. L., Esvelt, K. M.


& Church, G. M. Safeguarding CRISPR-Cas9 gene drives in yeast. _Nat. Biotechnol._ 33, 1250–1255 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Gantz, V. M. & Bier,


E. Genome editing. The mutagenic chain reaction: a method for converting heterozygous to homozygous mutations. _Science_ 348, 442–444 (2015). Article  CAS  PubMed  PubMed Central  Google


Scholar  * Gantz, V. M. et al. Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito _Anopheles stephensi_. _Proc. Natl Acad. Sci. USA_ 112,


E6736–E6743 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Hammond, A. et al. A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector


_Anopheles gambiae_. _Nat. Biotechnol._ 34, 78–83 (2016). Article  CAS  PubMed  Google Scholar  * Wright, O., Delmans, M., Stan, G. B. & Ellis, T. GeneGuard: a modular plasmid system


designed for biosafety. _ACS Synth. Biol._ 4, 307–316 (2015). Article  CAS  PubMed  Google Scholar  * Molin, S. et al. Conditional suicide system for containment of bacteria and plasmids.


_Nat. Biotechnol._ 5, 1315–1318 (1987). Article  CAS  Google Scholar  * Bej, A. K., Perlin, M. H. & Atlas, R. M. Model suicide vector for containment of genetically engineered


microorganisms. _Appl. Environ. Microbiol._ 54, 2472–2477 (1988). CAS  PubMed  PubMed Central  Google Scholar  * Knudsen, S. M. & Karlström, O. H. Development of efficient suicide


mechanisms for biological containment of bacteria. _Appl. Environ. Microbiol._ 57, 85–92 (1991). CAS  PubMed  PubMed Central  Google Scholar  * Poulsen, L. K., Larsen, N. W., Molin, S. &


Andersson, P. A family of genes encoding a cell-killing function may be conserved in all gram-negative bacteria. _Mol. Microbiol._ 3, 1463–1472 (1989). Article  CAS  PubMed  Google Scholar


  * Braat, H. et al. A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn’s disease. _Clin. Gastroenterol. Hepatol._ 4, 754–759 (2006). Article  CAS  PubMed  Google


Scholar  * Meinhardt, S. et al. Novel insights from hybrid LacI/GalR proteins: family-wide functional attributes and biologically significant variation in transcription repression. _Nucleic


Acids Res._ 40, 11139–11154 (2012). Article  CAS  PubMed  PubMed Central  Google Scholar  * Meinhardt, S. & Swint-Kruse, L. Experimental identification of specificity determinants in the


domain linker of a LacI/GalR protein: bioinformatics-based predictions generate true positives and false negatives. _Proteins_ 73, 941–957 (2008). Article  CAS  PubMed  PubMed Central 


Google Scholar  * Taylor, N. D. et al. Engineering an allosteric transcription factor to respond to new ligands. _Nat. Methods_ 13, 177–183 (2016). Article  CAS  PubMed  Google Scholar 


Download references ACKNOWLEDGEMENTS We thank E. Cameron for his critical review and editing of the manuscript. The work was supported by the Wyss Institute for Biologically Inspired


Engineering, the Paul G. Allen Frontiers Group, the Defense Threat Reduction Agency grant HDTRA1-14-1-0006, and Air Force Office of Scientific Research grant FA9550-14-1-0060. J.W.L. was


also supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2018R1C1B3007409), and by


the Marine Biotechnology Program (Marine BioMaterials Research Center) funded by the Ministry of Oceans and Fisheries, Korea. C.T.Y.C. was also supported by the University of Texas System


Rising STARs Program and by the Welch Foundation (grant # BP-0037). AUTHOR INFORMATION Author notes * These authors contributed equally: Jeong Wook Lee, Clement T. Y. Chan. AUTHORS AND


AFFILIATIONS * Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA Jeong Wook Lee, Shimyn Slomovic & James J. Collins * Department of Chemical


Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea Jeong Wook Lee * Institute for Medical Engineering & Science, Massachusetts Institute of


Technology (MIT), Cambridge, MA, USA Clement T. Y. Chan & James J. Collins * Department of Biological Engineering, MIT, Cambridge, MA, USA Clement T. Y. Chan & James J. Collins *


Synthetic Biology Center, MIT, Cambridge, MA, USA Clement T. Y. Chan & James J. Collins * Department of Biology, The University of Texas at Tyler, Tyler, TX, USA Clement T. Y. Chan *


Department of Chemistry and Biochemistry, The University of Texas at Tyler, Tyler, TX, USA Clement T. Y. Chan * Harvard–MIT Program in Health Sciences and Technology, Cambridge, MA, USA


James J. Collins * Broad Institute of MIT and Harvard, Cambridge, MA, USA James J. Collins Authors * Jeong Wook Lee View author publications You can also search for this author inPubMed 


Google Scholar * Clement T. Y. Chan View author publications You can also search for this author inPubMed Google Scholar * Shimyn Slomovic View author publications You can also search for


this author inPubMed Google Scholar * James J. Collins View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to James J.


Collins. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. ADDITIONAL INFORMATION PUBLISHER’S NOTE: Springer Nature remains neutral with regard to


jurisdictional claims in published maps and institutional affiliations. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Lee, J.W., Chan, C.T.Y.,


Slomovic, S. _et al._ Next-generation biocontainment systems for engineered organisms. _Nat Chem Biol_ 14, 530–537 (2018). https://doi.org/10.1038/s41589-018-0056-x Download citation *


Received: 03 May 2017 * Accepted: 09 March 2018 * Published: 16 May 2018 * Issue Date: June 2018 * DOI: https://doi.org/10.1038/s41589-018-0056-x SHARE THIS ARTICLE Anyone you share the


following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer


Nature SharedIt content-sharing initiative