Novel in situ base editing of gut bacteria - inconsistencies, gaps, and anticipated dangers on treated humans, animals, and the entire ecosystem

Recent years have seen an enormous rise in the “editing” of genomes in living organisms. In the openenvironment, this has raised the concern of unwanted mutations and adverse effects on non-targeted species. Aiming for a previously unattained goal, a very recent publication in Nature reports on the in situ base editing of targeted bacterial populations in the mouse gut. The genetic modifications of such bacteria rely on a novel delivery system via a synthetic virus. Such bacteriophages have been engineered to target different bacterial receptors to improve the delivery efficacy of a complex hybrid plasmid that carries the gene editor. This DNA cosmid is predicted to be non-replicative to “prevent” maintenance and dissemination of the synthetic payload. The authors report successful gene-editing in model pathogens, including some pathogenic strains.This paper gives an independent logical appraisal of the design of the synthetic editor, the experiments conducted, and their interpretation. This exposes several inconsistencies with the study and oddities which may, in part, stem from the fact that the authors are seemingly unaware of key dangers of gene editors and their risk assessment, and of related work that demonstrates the danger of microbial evolution in the open environment that may, in turn, foster the emergence of novel pathogens, and the difficulty of conducting microbial population analyses.The analysis also raises issues not mentioned in the paper, indicating the potential for serious consequences of exposed non-target organisms in the open environment or, when applied clinically, to adulterate the genetic makeup of the treated human or animal. In addition to the concern of potentially systemic dissemination and maintenance of the transgenes or products derived from them, urgent questions involve the type of these experiments - which resemble dangerous gain-of-function experiments on viruses and bacteria even though they seem to evade being defined as such. Beyond the potential of grave consequences on treated humans and animals, as well as the entire biosphere, the legal gap and lack of appropriate biosafety and biosecurity oversight may also enable illicit gene technologies and clandestine biological weapons programs.