Abstract
Improvements in DNA-editing technologies have enabled engineering of microorganisms at the gene, network and genome level, helping to elucidate causal links between genotypes and phenotypes, and facilitating the targeted exploration of complex phenotype landscapes. DNA sequencing and genome engineering are synergistic technologies: understanding genetic and phenotypic diversity establishes a platform for pursuing many goals in biological design. Multiplex genome modification techniques have enabled combinatoric genomic variations across populations, exploring large numbers of genotype–phenotype landscapes in living cells. The combination of DNA synthesis and in vivo genome editing establishes the ability to fundamentally redesign systems from refactored pathways to whole-genome recoding. The future of genome editing will require the combination of de novo synthesis and in vivo genome evolution integrated with functional screens and selections to isolate variants exhibiting a desired phenotype.

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