New Israeli tech gives accuracy boost to microscopic scissors for DNA editing

The CRISPR technique snips DNA, but what if it cuts the wrong location in the genome without scientists realizing? Software innovation provides alerts

Nathan Jeffay is The Times of Israel's health and science correspondent

Scientists analyzing DNA helix and editing genome within organisms, CRISPR technology (elenabs via iStock by Getty Images)
Scientists analyzing DNA helix and editing genome within organisms, CRISPR technology (elenabs via iStock by Getty Images)

Israeli scientists have developed a “quality assurance” method for genome editing, which they say has the power to make it easier to translate DNA technologies from theory to treatments.

The CRISPR genome editing system works by cutting DNA with microscopic “scissors” and fixing it. The method is deployed to address some genetic disorders, and there are huge efforts to expand its use.

But one of the teething troubles is accuracy. “Like every house has an address you use to find it, every gene has an ‘address’ that we use to target CRISPR editing, but sometimes there is a lack of accuracy and the tiny ‘scissors’ go to the wrong place,” said molecular biologist Dr. Ayal Hendel of Bar Ilan University.

He has pioneered a new method for assessing, with an unprecedented level of accuracy, how many mistakes creep in when a genome editing tool is used, and where the mistakes occur. An academic paper on the breakthrough is due to appear on Monday in the peer-reviewed journal Nature Communications.

Hendel said his tech — software that is already available for download — will give scientists a chance to fix errors quickly, potentially saving them months they may otherwise invest in developing inaccurate tools. It is also intended to prevent the false alarms that currently slow research by flagging problems that don’t exist.

An illustration of the genome editing technique, with scissors showing where DNA is to be “cut.” (Tel Aviv University)

Hendel said that his innovation allows a new level of precision in the assessment of tools before they are submitted for clinical trials.

He hopes it will help speed up the search for cures for sickle cell disease and severe combined immunodeficiency, which is often called “bubble boy disease.”

“This can help with the development of genome editing as it will be much easier to test new tools and then submit them for approval, or quickly realize there is a problem and send them for redevelopment,” he told The Times of Israel. “It can significantly speed up the time it takes from concept to medical use.”

Dr. Ayal Hendel (courtesy of Dr. Ayal Hendel)

There are currently machines that look for problems with a planned genome edit, but they are prone to pick up existing complications in a patient’s’ DNA and mistake this for a problem with the edit.

Together with Bar Ilan colleagues and Zohar Yakhini, a professor at IDC Herzliya and the Technion-Israel Institute of Technology, Hendel has developed software that takes readings from existing machines and eliminates 99 percent of “false positives.” This means it discounts almost all problems that appear to arise from DNA editing but which are actually unrelated to the edit.

At the same time, it analyzes the machines’ result in such a way that it catches “false negatives,” namely instances when there appears to be no problem with the edit, but there is.

“Essentially, we’re getting rid of the noise that currently exists when we try to assess the accuracy of genome editing, and reducing instances when we miss problems,” said Hendel.

He said that the technology will push forward the use of CRISPR.

“It’s relevant when someone develops a CRISPR approach to treat or cure a genetic disease, using the tiny scissors, and they want to prove the accuracy of the tool to regulators like America’s Food and Drug Administration.

“They need to show that it cuts the DNA in the right place, and not in the wrong place. They can use our tool to assess and illustrate the extent of accuracy, and if the accuracy is not up to standard, they can redesign their technology.

“This can potentially help support a growing field of research by testing new breakthroughs with high precision,” he said.

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