Biocontainment of genetically modified organisms by synthetic protein design

Abstract

Genetically modified organisms (GMOs) are increasingly deployed at large scales and in open environments. Genetic biocontainment strategies are needed to prevent unintended proliferation of GMOs in natural ecosystems. Existing biocontainment methods are insufficient either because they impose evolutionary pressure on the organism to eject the safeguard, because they can be circumvented by environmentally available compounds, or because they can be overcome by horizontal gene transfer (HGT). Here we computationally redesign essential enzymes in the first organism possessing an altered genetic code to confer metabolic dependence on nonstandard amino acids for survival. The resulting GMOs cannot metabolically circumvent their biocontainment mechanisms using environmentally available compounds, and they exhibit unprecedented resistance to evolutionary escape via mutagenesis and HGT. This work provides a foundation for safer GMOs that are isolated from natural ecosystems by reliance on synthetic metabolites.

Anomaly handling and the politics of gene drives

“…This strategy of developing technical approaches to fit regulatory and policy goals, including safety, appears frequently in bioengineering (Isaacs et al 2011;Mandell et al 2015;Rovner et al 2015), and is receiving significant attention within gene drive research and development. For example, a majority of scientists engaged in early gene drive development outlined a set of confinement strategies to be employed whenever gene drive work is conducted (Akbari et al 2015).…”

Systems metabolic engineering as an enabling technology in accomplishing sustainable development goals

“…SysME can be employed to develop biocontainment system to avoid uncontrolled proliferation of the engineered organisms that can possibly perturb the natural ecosystem. Early biocontainment systems developed used auxotrophs in which only cells that have been supplied with exogenous metabolites (Steidler et al ., 2003; Wright et al ., 2013) or non‐natural amino acids (Mandell et al ., 2015; Rovner et al ., 2015) could grow. Of notable engineering feats in biocontainment systems are microbial kill switches with synthetic regulatory circuits developed recently (Chan et al ., 2016).…”

Whole genome synthesis: from poliovirus to synthetic yeast

“…Therefore, making an organism's genome, which contains all information a living organism requires, is a good alternative. Second, despite the fact that modifying one genome is facilitated by recent advances in genomeediting technologies, it still takes years to make a small but pervasive change throughout the genome such as eliminating one codon from E. coli [9][10][11][12][13][14]. Third, there are lots of things that may not be feasible, if not impossible, to test without a designer genome bearing these pervasive changes.…”

“…Recently, CRISPR-Cas9 gene drive systems were designed to prevent unintended genome editing occurring through the escape of lab strains [46]. Studies in bacterial systems have developed genome safeguards based on the TAG codon-engineered strains (REcoli) and orthogonal tRNA synthetase systems [12,13], and on riboregulation of essential genes [47].…”