OMG, GMO! Intrinsic biosafety for the here and now

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Ollie Wright, Guy-Bart Stan, Tom Ellis

Imperial College, United Kingdom

As applications of synthetic biology move from the realms of ideas and laboratory-confined research towards real-world implementation, concerns over biosafety are being raised. Re-engineered, self-replicating cells may produce undesired consequences if they escape or overwhelm their intended environment, or if the synthetic information they contain (often plasmid-borne) is utilised by indigenous organisms. To address these biosafety issues, multiple mechanisms for constraining microbial replication and horizontal gene transfer have been proposed. These include the use of host-construct dependencies such as toxin-antitoxin pairs, conditional plasmid replication, or auxotrophies. While refactoring of the existing genetic code or tailoring of orthogonal systems offer future promise of more stringent ‘firewalls’ between natural and synthetic cells, here we focus on what level of biosafety can be achieved currently using the approaches cited above. To maximise system redundancy, such devices are utilised in parallel. An in vivo screen with a high selection coefficient for horizontal gene transfer is introduced, and subsequently used to assess overall efficacy of the systems for biocontainment. Comparison of these results with the theoretical levels desired for maximal biosafety is also made.