A team of scientists from the United Kingdom has discovered that the famous and hopeful CRISPR / Cas9 gene editing technology can cause more damage to cells than previously believed, according to a study published in the journal Nature.
Thus, the new research suggests that we should not rush into using CRISPR genome editing within the human body. Not yet. The technique can cause large deletions or even rearrangements of DNA, says Allan Bradley of the Wellcome Sanger Institute (UK), which means that some CRISPR-based therapies may not be as safe as we thought.
To reach this conclusion, the experts carried out an extensive systematic study in both mice and humans, verifying that CRISPR / Cas9 frequently caused extensive mutations. As a consequence, many genetic cells underwent remarkable rearrangements, producing both “deletions” and “insertions” of DNA.
The CRISPR genome editing technique is revolutionizing biology, allowing us to create new varieties of plants and animals and develop treatments for a wide range of diseases.
The CRISPR / Cas9 technique works by cutting a cell’s DNA at a specific location. When the cell repairs the damage, some letters of DNA change at this point, an effect that can be exploited to turn genes off.
At least that’s how it’s supposed to work. But in studies of mice and human cells, Bradley’s team found that in about a fifth of cells, CRISPR caused deletions or rearrangements of more than 100 letters of DNA. These changes can be 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 within the human body. If the experts are right, there is a possibility that some of these cells will turn cancerous.
“There is a risk of causing cancer at some point in a patient’s life,” says Bradley. “We need to understand more before rushing to human clinical trials.”
The finding comes just a month after another team reported that there is a risk of cancer due to the genetic modification of embryonic stem cells, for a completely different reason.
Many variations of the CRISPR technique are currently being developed, including base editors that alter specific DNA letters and do not completely cut DNA. These methods can be much safer. Some groups are also using modified forms of CRISPR to monitor how active a gene is rather than directly altering a gene’s DNA.
Reference: Repair of CRISPR – Cas9-induced double-stranded breaks leads to large deletions and complex rearrangements, Nature Biotechnology (2018). DOI: 10.1038 / Nbt.4192, https://www.nature.com/articles/Nbt.4192
