CRISPR gene editing is not quite as precise and as safe as thought

**Mingle** · 07-17-2018, 01:44 AM

A study of CRIPSR suggests we shouldn’t rush into trying out CRISPR genome editing inside people’s bodies just yet. The technique can cause big deletions or rearrangements of DNA, says Allan Bradley of the Wellcome Sanger Institute in the UK, meaning some therapies based on CRISPR may not be quite as safe as we thought.

The CRISPR genome editing technique is revolutionising biology, enabling us to create new varieties of plants and animals and develop treatments for a wide range of diseases.

The CRISPR Cas9 protein works by cutting the DNA of a cell in a specific place. When the cell repairs the damage, a few DNA letters get changed at this spot – an effect that can be exploited to disable genes.

At least, that’s how it is supposed to work. But in studies of mice and human cells, Bradley’s team has found that in around a fifth of cells, CRISPR causes deletions or rearrangements more than 100 DNA letters long. These surprising changes are sometimes thousands of letters long.

Cancer risk
This finding is not a problem for the purposes for which CRISPR is currently being used. But some groups are developing treatments that would involve using CRISPR to edit billions of cells inside the human body. If Bradley is right, there’s a chance that a few of these cells might turn cancerous.

“There’s a risk of causing cancer sometime in a patient’s lifetime,” says Bradley. “We need to understand more before rushing into human clinical trials.”

“I do believe the findings are robust,” says Gaetan Burgio of the Australian National University, an expert on CRISPR who has debunked previous studies questioning the method’s safety. “This is a well-performed study and fairly significant.”

The finding comes just a month after another team reported that there was a cancer risk from gene-editing embryonic stem cells, for a quite different reason. It was also claimed last year that CRISPR causes lots of mutations far from the target site, but Burgio and others pointed out that the study was seriously flawed and it has since been retracted.

Newer techniques
“Overall, this adds more safety challenges to CRISPR-based gene therapies but it doesn’t compromise its use,” says Burgio of the new findings.

Many variations of the CRISPR technique are currently being developed, including base editors that alter specific DNA letters and nickases that do not completely sever the DNA. These methods may prove to be far safer. Some groups are also using modified forms of CRISPR to control how active a gene is instead of directly altering a gene’s DNA.

So why have the thousands of teams using CRISPR failed to discover this before? Because they have been looking for small mutations in a narrow region around the target site. If that whole region is deleted, this approach makes it appear as if there have been no mutations at all. “You find what you look for,” says Bradley.

https://newscientist.com/article/217...fe-as-thought/