Researchers have refined CRISPR-Cas9, the breakthrough genome editing system, to dramatically cut down on errors in the editing process.

The refinements have reduced what is known as “off-target editing” to an undetectable level in the species they were tested on, addressing one of the biggest technical issues with the system.

It is hoped that the improvement will allay fears relating to genome editing, which has been the subject of significant ethical concerns, although the researchers, from Harvard and MIT, are under no illusions about resistance to the technology.

“Many of the safety concerns are related to off-target effects,” said Feng Zhang, study co-author and M. Keck Career Development Professor of Biomedical Engineering in the departments of Brain and Cognitive Sciences and Biological Engineering at the Massachusetts Institute of Technology.

“We hope the development of eSpCas9 will help address some of those concerns, but we certainly don’t see this as a magic bullet.”

At present CRISPR-Cas9 works by making targeted modifications to a cell’s DNA using the enzyme Cas9. This protein is able to precisely modify a given location in the DNA by using short RNA as a kind of signpost: the given short RNA will have the same sequence as the location targeted.

It’s a highly effective system that allows Cas9 to cut its target site with extreme efficiency, but there is a flaw: once the Cas9 gets inside the cell, it can bind to and cut other sites that are not the intended target, an action that is known as “off-target editing”.

This seemingly minor error can be disastrous, resulting in changes to gene expressions or rendering genes entirely non-functioning, which in turn can cause issues such as cancer.

The researchers’ breakthrough concerns the creation of an improved version of Cas9, which cuts unintended sites dramatically less, to the point where off-target editing was at undetectable levels in the sample cases used to test the improved enzyme, known as “enhanced” S. pyogenes Cas9 (eSpCas9).

This enhanced enzyme has three mutated amino acids, which in the original Cas9 are positively charged, but were replaced with neutral versions, a change that has had a significant impact on the level of off-target editing.

Having published a paper in the journal Science today about the breakthrough, the researchers are now making eSpCas9 immediately available to researchers around the world.

They also believe that other variants of the CRISPR genome editing system, which use different proteins, could also benefit from a similar adjustment.

In time, the research could even prove vital in using CRISPR to tackle genetic disorders in humans, although this is still a considerable way off.

“The field is advancing at a rapid pace, and there is still a lot to learn before we can consider applying this technology for clinical use,” said Zhang.