A bumpy road ahead for genetic biocontainment

George, Dalton R.; Danciu, Mark; Davenport, Peter W.; Lakin, Matthew R.; Chappell, James; Frow, Emma K.

doi:10.1038/s41467-023-44531-1

Cited by 4 publications

(1 citation statement)

References 41 publications

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“…In this context, genetic biocontainment involves manipulating microbe genomes to prevent the engineered organism's unintended proliferation, spread, or persistence outside the designated environment [36,37]. Biocontainment strategies have been devised for different microorganisms using genetic code modification [38,39], auxotrophy [40,41], kill switches [42,43], dependence on unnatural amino acids [44,45] and combinations of different systems [46,47].…”

Section: Introductionmentioning

confidence: 99%

Designing a simple and efficient phage biocontainment system using the amber suppressor initiator tRNA

Tsoumbris,

Vincent,

Jaschke

2024

Preprint

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Multidrug-resistant infections are becoming increasingly prevalent worldwide. One of the fastest emerging alternative and adjuvant therapies being proposed is phage therapy. Naturally-isolated phages are used in the vast majority of phage therapy treatments today. Engineered phages are being developed to enhance the effectiveness of phage therapy, but concerns over their potential escape remains a salient issue. To address this problem, we designed a biocontained phage system based on conditional replication using amber stop codon suppression. This system can be easily installed on any natural phage with a known genome sequence. To test the system, we mutated the start codons of three essential capsid genes in the phage φX174 to the amber stop codon (TAG). These phages were able to efficiently infect host cells expressing the amber initiator tRNA, which suppresses the amber stop codon and initiates translation at TAG stop codons. The amber phage mutants were also able to successfully infect host cells and reduce their population on solid agar and liquid culture but could not produce infectious particles in the absence of the amber initiator tRNA or complementing capsid gene. We did not detect any growth-inhibiting effects on E. coli strains known to lack a receptor for φX174, and we show that engineered phages have a limited propensity for reversion. The approach outlined here may be useful to control engineered phage replication in both the lab and clinic.

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Section: Introductionmentioning

confidence: 99%

Designing a simple and efficient phage biocontainment system using the amber suppressor initiator tRNA

Tsoumbris,

Vincent,

Jaschke

2024

Preprint

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Engineered bacterial therapeutics with material solutions

Dey,

Sankaran

2024

Trends in Biotechnology

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Cellular Site-Specific Incorporation of Noncanonical Amino Acids in Synthetic Biology

Niu,

Guo

2024

Chem. Rev.

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Over the past two decades, genetic code expansion (GCE)-enabled methods for incorporating noncanonical amino acids (ncAAs) into proteins have significantly advanced the field of synthetic biology while also reaping substantial benefits from it. On one hand, they provide synthetic biologists with a powerful toolkit to enhance and diversify biological designs beyond natural constraints. Conversely, synthetic biology has not only propelled the development of ncAA incorporation through sophisticated tools and innovative strategies but also broadened its potential applications across various fields. This Review delves into the methodological advancements and primary applications of sitespecific cellular incorporation of ncAAs in synthetic biology. The topics encompass expanding the genetic code through noncanonical codon addition, creating semiautonomous and autonomous organisms, designing regulatory elements, and manipulating and extending peptide natural product biosynthetic pathways. The Review concludes by examining the ongoing challenges and future prospects of GCE-enabled ncAA incorporation in synthetic biology and highlighting opportunities for further advancements in this rapidly evolving field.

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A bumpy road ahead for genetic biocontainment

Abstract: While the research community continues to develop novel proposals for intrinsic biocontainment of genetically engineered organisms, translation to real-world deployment faces several challenges.

Cited by 4 publications

References 41 publications

Designing a simple and efficient phage biocontainment system using the amber suppressor initiator tRNA

Designing a simple and efficient phage biocontainment system using the amber suppressor initiator tRNA

Engineered bacterial therapeutics with material solutions

Cellular Site-Specific Incorporation of Noncanonical Amino Acids in Synthetic Biology

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