Commentary – Nature – Synthetic biology: Building genetic containment

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Synthetic biology: Building genetic containment
Haynes KA (2016) Nat Chem Biol. 12:55-56.

Dr. Karmella Haynes’ News & Views article discussing Chan et al.’s recent work on genetic containment of genetically modified organisms has been published in Nature Chemical Biology, part of the Nature Publishing Group.

Since the 1980s, scientists have worked on designing genetic codes to reinforce containment and control of genetically engineered microbes. New mechanistic studies of “deadman” and “passcode” gene circuits provide a flexible platform to build new safety switches.

The News & Views piece [1] explains the importance of including control mechanisms (a.k.a. biocontainment) in the DNA of genetically engineered microbes (single-celled organisms). The central topic of the piece is the recent paper “‘Deadman’ and ‘Passcode’ microbial kill switches for bacterial containment” [2] by Chan et al. from the Collins group at MIT & Harvard. They explored how custom-built kill switches could be fine-tuned using the intrinsic properties of the building blocks within the switch.

News & Views articles are too short to include all of the best work on a subject area, so I will highlight a few recent and exciting advances on biocontainment here. In the journal PNAS, Cai et. al. from the Beoke group (and the Yeast 2.0 project) reported a system that made genetically modified yeast strictly dependent on a pair of compounds (galactose/ glucose and estradiol) [3 open access]. The compounds are required to allow yeast to maintain histone protein levels, which are essential for cell survival. In Plant Biotechnology, Young and Purton reported the engineering of chloroplast DNA to prevent synthetic DNA from being transferred from genetically modified Chlamydomonas, a single-celled algae, into unintended hosts [4 open access]. In NAR, Gallagher et. al. from the Isaacs group used a combination of riboregulators, auxotrophy, and a toxic gene (nuclease) to reduce the chance of kill switch failure and escape of genetically modified bacteria. They reported escape rates as low as one in one trillion (far lower than the NIH recommendation of one in one hundred million) [5 open access]. I highly recommend these recent articles to anyone who wants to learn more about how engineers are building safety into genetically modified systems.

Articles with active links in the reference list below can be accessed for free online.

  1. Haynes KA. (2016) Synthetic biology: Building genetic containment. Nat Chem Biol. 12:55-56.
  2. Chan CT, Lee JW, Cameron DE, Bashor CJ, Collins JJ. (2016) ‘Deadman’ and ‘Passcode’ microbial kill switches for bacterial containment. Nat Chem Biol. 12:82-86.
  3. Cai Y, Agmon N, Choi WJ, Ubide A, Stracquadanio G5 Caravelli K, Hao H, Bader JS, Boeke JD. (2015) Intrinsic biocontainment: multiplex genome safeguards combine transcriptional and recombinational control of essential yeast genes. PNAS. 2:1803-1808.
  4. Young RE, Purton S. (2015) Codon reassignment to facilitate genetic engineering and biocontainment in the chloroplast of Chlamydomonas reinhardtii. Plant Biotechnol. epub ahead of print.
  5. Gallagher RR, Patel JR, Interiano AL, Rovner AJ, Isaacs FJ. (2015) Multilayered genetic safeguards limit growth of microorganisms to defined environments. NAR. 43:1945-1954.

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