Refactored genetic codes enable bidirectional genetic isolation

Zürcher, Jérôme F.; Robertson, Wesley E.; Kappes, Tomás; Petris, Gianluca; Elliott, T. S. J.; Salmond, George P. C.; Chin, Jason W.

doi:10.1126/science.add8943

Cited by 37 publications

(32 citation statements)

References 45 publications

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“…Recent studies also show the GRO with altered genetic code is resistant to viral infections and transfer of mobile genetic elements. 29,30 Despite these exciting achievements using E. coli as the model organism, much less progress has been made in the eukaryotic system, which is more suitable for expression of proteins that require post-translational modifications and folding. The genome-wide substitution of the TAG stop codon by TAA in the design of Sc2.0 yeast aims to free a blank codon for GCE; however, it is still challenging to completely repurpose the specificity of eRF1, the single omnipotent release factor required for cell viability.…”

Section: ■ Viability and Functional Testingmentioning

confidence: 99%

“…By introducing the orthogonal aminoacyl-tRNA synthetase/tRNA pairs into the GRO, robust biocontainment systems relying on ncAA have been developed, which could prohibit unwanted propagation of GRO in open environments. Recent studies also show the GRO with altered genetic code is resistant to viral infections and transfer of mobile genetic elements. , …”

Section: Applications Of Synthetic Genomicsmentioning

confidence: 99%

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Synthetic Genomics: Repurposing Biological Systems for Applications in Engineering Biology

Fu,

Shen

2024

ACS Synth. Biol.

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Substantial improvements in DNA sequencing and synthesis technologies and increased understanding of genome biology have empowered the development of synthetic genomics. The ability to design and construct engineered living cells boosted up by synthetic chromosomes provides opportunities to tackle enormous current and future challenges faced by humanity and the planet. Here we review the progresses, considerations, challenges, and future direction of the "design−build−test−learn" cycle used in synthetic genomics. We also discuss future applications enabled by synthetic genomics as this emerging field shapes and revolutionizes biomanufacturing and biomedicine.

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Section: ■ Viability and Functional Testingmentioning

confidence: 99%

Section: Applications Of Synthetic Genomicsmentioning

confidence: 99%

Synthetic Genomics: Repurposing Biological Systems for Applications in Engineering Biology

Fu,

Shen

2024

ACS Synth. Biol.

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“…Rare codons could also be systematically removed from the M. florum genome (Isaacs et al, 2011;Fredens et al, 2019), allowing codon reassignment and strict biocontainment measures. Artificial genetic codes could be developed and tested by swapping tRNA anticodons, thereby improving resistance to viruses and mobile genetic genetic elements (Zürcher et al, 2022;Nyerges et al, 2023) (Figure 2F). Genes with related functions could be regrouped into modules, reorganizing and streamlining the entire genome for engineering purposes (Hutchison et al, 2016;Coradini et al, 2020) (Figure 2G).…”

Section: Is the Genome Of M Florum Minimal?mentioning

confidence: 99%

Mesoplasma florum: a near-minimal model organism for systems and synthetic biology

Matteau,

Duval,

Baby

et al. 2024

Front. Genet.

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Mesoplasma florum is an emerging model organism for systems and synthetic biology due to its small genome (∼800 kb) and fast growth rate. While M. florum was isolated and first described almost 40 years ago, many important aspects of its biology have long remained uncharacterized due to technological limitations, the absence of dedicated molecular tools, and since this bacterial species has not been associated with any disease. However, the publication of the first M. florum genome in 2004 paved the way for a new era of research fueled by the rise of systems and synthetic biology. Some of the most important studies included the characterization and heterologous use of M. florum regulatory elements, the development of the first replicable plasmids, comparative genomics and transposon mutagenesis, whole-genome cloning in yeast, genome transplantation, in-depth characterization of the M. florum cell, as well as the development of a high-quality genome-scale metabolic model. The acquired data, knowledge, and tools will greatly facilitate future genome engineering efforts in M. florum, which could next be exploited to rationally design and create synthetic cells to advance fundamental knowledge or for specific applications.

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“…Likewise, reassignment to endogenous amino acids can be used to create two-way barrier to genetic interaction with natural organisms. 67 However, there are constraints surrounding tRNA crosstalk and the dependence of many aminoacyl-tRNA synthetases on the anticodon for tRNA recognition. Thistype of recoding may find itself in tension with the goals of biosecurity screening of synthetic DNA.…”

Section: Genetic Safeguardsmentioning

confidence: 99%