Scientists have designed a genome processing tool that the bacterial population in Darmmikrobiom Living mice can modify 1 .

The tool-a kind of "base editor"-changed the target gene in more than 90% of a Escherichia coli colony in the mouse arm, without the changed gene to form potentially harmful copies of itself. "We dreamed of being able to," says Xavier, a synthetic biologist, the Eligo Bioscience, a biotechnology company in Paris. The results were published in Nature today.

Several research teams have tried to make genetic changes in intestinal bacteria of mice, but to achieve this in the body was a challenge. 4 , 3 , 2 . So far, base editors that exchange a nucleotide base for another-for example converting an A to a G-without breaking the DNA double strand, are not able to modify sufficiently the target bacterial population in order to be effective. This is because the vectors in which they were delivered only target receptors that are common in bacteria that were cultivated in the laboratory.

innovative delivery system

To overcome these hurdles, constructed duports and his colleagues a delivery vehicle using components of a bacteriophage -a virus that infects bacteria -to different e. Coli receptors that are expressed in the intestinal environment. This vector wore a base editor that specific e. Coli -Gene targeted. The researchers also refined the system to prevent the edited genes from replicating and spreading.

The team introduced the base editor into mice and used it to a e. Change coli -Gen that produces β lactic masis-enzymes that promote bacterial resistance to different types of antibiotics. Around 93% of the targeted bacteria were edited about eight hours after the treatment.

Then the researchers adapted the base editor, so that he a e. Coli -Gengen could modify that produces a protein that is supposed to play a role in several neurodegenerative and autoimmune diseases. The proportion of edited bacteria was around 70%three weeks after the treatment. In the laboratory, the scientists were also able to use the tools to strain stems from e. Coli and Klebsiella pneumoniae that can cause pneumonia. This indicates that the editing system can be adapted to different bacterial strains and types.

This base sedation system represents a “critical progress” in the development of tools that can modify bacteria directly in the intestine, says Chase Beisel, a chemical engineer at the Helmholtz Institute for RNA-based infection research in Würzburg, Germany. The study "opens up the opportunity to work on microbes to combat diseases while preventing the manipulated DNA," he adds.

The next step of duports and his colleagues is the development of mouse models with diseases caused by the microbiome to measure whether specific gene edits have a positive influence on their health.