A new DNA-editing mechanism discovered in bacteria may outdo CRISPR

A unique bacterial molecule could allow scientists to reengineer genomes, enabling them to insert, delete or flip large segments of DNA. This technique is described in three recent papers Nature and Nature Communications, using jumping genes that naturally insert themselves into genomes.

According to Sandro Fernandez Atteide, a structural biologist at the University of Sydney in Australia and an author on the Nature Communications paper, “If it works in other cells, it could be a game changer. This opens up a new field in gene editing.

This system, guided by a 'bridge’ RNA, has successfully edited genes in bacteria and in vitro, although its efficiency in human cells remains uncertain. If modifiable, its small size and ability to modify DNA sequences thousands of bases long could revolutionize gene editing.

CRISPR-Cas9 has often faced misleading headlines. It can rewrite small gene segments but is not the versatile cut-and-paste system that some stories suggest. Typically, it only replaces a few DNA bases by first breaking the DNA and using the cell’s repair systems. This can cause unexpected genetic damage.

Researchers are turning to multiple gene editing for targeted therapies

As CRISPR advances in human medicine, researchers aim to improve their gene-editing tools to insert entire genes or multiple genes into specific locations. This approach could lead to treatments for individuals with multiple mutations in one gene, streamlining treatment. Also, editing multiple genes enables the engineering of immune cells to fight cancer from different angles, ensuring precise gene insertion into the genome.

Patrick Hsu, a bioengineer at the nonprofit Ark Institute in Palo Alto, California, and co-author of two Nature papers, emphasized the future goal of engineering whole regions of the genome rather than individual sites.

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To find suitable tools, Hsu and his colleagues investigated various enzymes that help move mobile DNA elements between locations in bacteria. They focused on a specific group of transposable elements, specifically called IS110.

Enables versatile DNA modifications

IS110 enzymes use a unique RNA-based system for targeting, the team discovered. One end of the RNA binds to the DNA segment intended to insert, while the other end binds the DNA fragment at the insertion site in the genome. This RNA acts as a bridge between the two DNA segments, and the team calls these molecules 'bridge RNAs’.

One sequence identifies the target location in the genome, similar to CRISPR, and the other specifies the segment of DNA to be altered. This system adds, deletes, or modifies DNA sequences of any length.

Current methods achieve these tasks, but they often require multiple steps and leave unwanted DNA fragments. Hsu noted that bridge editing avoids scarring, providing precise control over gene manipulation.

This ability goes beyond genetic modification; It can modify the genomes of plants and animals to a large extent.

„What we want to do is go beyond inserting individual genes to perform chromosome-level genetic engineering,” noted Hsu.

Published in Research Nature On June 27.

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About the editor

Bojan Stojkowski Bojan Stojkovski is a freelance journalist based in Skopje, North Macedonia, covering foreign policy and technology for more than a decade. His work has appeared in Foreign Policy, ZDNet, and Nature.

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