Inspired by bacteria’s defense strategies

Study in Nature Biotechnology: Scientists from the Beisel lab and partner institutions pioneer a novel method for genome editing

2025-09-18

(Press-News.org) Targeted editing of genetic information has advanced at an extraordinary pace in recent years. Tools such as the CRISPR-Cas9 “gene scissors” and base editing—a technique that makes precise, single-letter changes to DNA without cutting it—have already become standard in research and clinical development. These technologies are being used to treat genetic disorders, enhance crop resistance, and engineer bacteria for biotechnological purposes.

Turning the battle between bacteria and viruses into scientific progress

Researchers at the Helmholtz Institute for RNA-based Infection Research (HIRI), a site of the Braunschweig Helmholtz Centre for Infection Research (HZI) in cooperation with the Julius-Maximilians-Universität Würzburg (JMU), have developed a new method for precisely editing DNA. The HIRI team also cooperated with North Carolina State University in the USA and ETH Zurich in Switzerland. Their aim was to make genetic changes in bacteria, plants, and human cells even more accurate and gentle. The results have now been published online ahead of print in the journal Nature Biotechnology.

The team took inspiration from a natural bacterial defense system against viruses known as bacteriophages. To fight off these invaders, bacteria use two enzymes, DarT2 and DarG. During a viral infection, DarT2 attaches a chemical marker to the DNA, blocking replication and halting viral spread. In the absence of a threat, DarG shuts down DarT2 and actively removes the marker. This finely tuned mechanism helps prevent the virus from spreading—and now serves as the foundation for a new genome editing approach.

This newly developed form of attachment has been named “append editing” by the researchers. “For the first time, this allows us to achieve new types of genetic modifications not possible with previous methods,” the scientists explain.

To understand the mechanism, DNA can be imagined as a notebook in which each page consists of a long chain of letters. While traditional gene-editing techniques typically remove or replace individual letters within this chain, append editing introduces a small chemical group—ADP-ribose molecules—at a specific site. This addition functions like a “sticky note” affixed to a particular letter. The chemical marker convinces the cell to change this DNA with high precision and minimal disruption. The type of change, however, depended on the organism in which it was introduced.

“DarT2”—Pioneering a New Era of Genome Editing

Unlike previous technologies, where the same tools produce similar results across all organisms, the effects of the append editing method were different between bacteria and eukaryotes, such as fungi, plants, and human cells. „We observed that append editing led to the incorporation of large edits in bacteria based on a provided template, while in eukaryotic cells, the modified DNA base changed identity,” explains Chase Beisel, affiliated department head at HIRI. „This was one of the most surprising findings—that the outcome of DNA repair could be very different between organisms,” adds Constantinos Patinios, a former postdoc in Beisel’s lab.

Researchers see numerous potential applications for this tool. “Our append editing method greatly expands the toolkit of genome research and opens new doors for precision biotechnology and medical therapy development,” says Darshana Gupta, a doctoral student at HIRI. Specifically, microbes could be modified in a targeted manner—for example, to optimize naturally beneficial bacteria in the human body or to study pathogens more effectively. In human cells, precise editing could one day help to gently correct inherited diseases and provide new insights into DNA repair processes.

Further research is still needed before such applications can reach clinical practice. However, the scientists are confident: “DarT2 is another great example of the use of bacterial defenses in genome research,” says Harris Bassett, who is completing his PhD in Beisel’s lab.

Funding
The work was supported by the U.S. National Institutes of Health, the European Research Council (ERC) via a Consolidator Grant and under the EU Horizon 2020 program, the North Carolina Biotechnology Center, as well as a collaborative research project with the agricultural company Syngenta. Additional support came from doctoral fellowships awarded by the German Academic Exchange Service (DAAD), a fellowship from the Vogel Foundation Dr Eckernkamp, and the international graduate program “RNAmed – Future Leaders in RNA-Based Medicine” of the Elite Network of Bavaria. Further funding was provided by the U.S. National Science Foundation (NSF), the NOMIS Foundation, the Lotte and Adolf Hotz-Sprenger Foundation, and the Swiss National Science Foundation (SNSF).

Text: Jörg Fuchs

This press release is also available on our website: https://www.helmholtz-hzi.de/en/media-center/newsroom/news-detail/inspired-by-bacterias-defense-strategies/

Helmholtz Institute for RNA-based Infection Research:
The Helmholtz Institute for RNA-based Infection Research (HIRI) is the first institution of its kind worldwide to combine ribonucleic acid (RNA) research with infection biology. Based on novel findings from its strong basic research program, the institute’s long-term goal is to develop innovative therapeutic approaches to better diagnose and treat human infections. HIRI is a site of the Braunschweig Helmholtz Centre for Infection Research (HZI) in cooperation with the Julius-Maximilians-Universität Würzburg (JMU) and is located on the Würzburg Medical Campus. More information at www.helmholtz-hiri.de.

Helmholtz Centre for Infection Research:
Scientists at the Helmholtz Centre for Infection Research (HZI) in Braunschweig and its other sites in Germany are engaged in the study of bacterial and viral infections and the body’s defense mechanisms. They have a profound expertise in natural compound research and its exploitation as a valuable source for novel anti-infectives. As member of the Helmholtz Association and the German Center for Infection Research (DZIF) the HZI performs translational research laying the ground for the development of new treatments and vaccines against infectious diseases. www.helmholtz-hzi.de/en

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Inspired by bacteria’s defense strategies

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