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Use of genetically modified bacteria for drug delivery in humans: Revisiting the safety aspect.


ABSTRACT: The use of live, genetically modified bacteria as delivery vehicles for biologics is of considerable interest scientifically and has attracted significant commercial investment. We have pioneered the use of the commensal gut bacterium Bacteroides ovatus for the oral delivery of therapeutics to the gastrointestinal tract. Here we report on our investigations of the biological safety of engineered B. ovatus bacteria that includes the use of thymineless death as a containment strategy and the potential for the spread of transgenes in vivo in the mammalian gastrointestinal tract. We demonstrate the ability of GM-strains of Bacteroides to survive thymine starvation and overcome it through the exchange of genetic material. We also provide evidence for horizontal gene transfer in the mammalian gastrointestinal tract resulting in transgene-carrying wild type bacteria. These findings sound a strong note of caution on the employment of live genetically modified bacteria for the delivery of biologics.

SUBMITTER: Wegmann U 

PROVIDER: S-EPMC5442108 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Use of genetically modified bacteria for drug delivery in humans: Revisiting the safety aspect.

Wegmann Udo U   Carvalho Ana Lucia AL   Stocks Martin M   Carding Simon R SR  

Scientific reports 20170523 1


The use of live, genetically modified bacteria as delivery vehicles for biologics is of considerable interest scientifically and has attracted significant commercial investment. We have pioneered the use of the commensal gut bacterium Bacteroides ovatus for the oral delivery of therapeutics to the gastrointestinal tract. Here we report on our investigations of the biological safety of engineered B. ovatus bacteria that includes the use of thymineless death as a containment strategy and the poten  ...[more]

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