The much-hyped editing tool, CRISPR-Cas9 has already revolutionized the fields of genetics and medicine. The technique, which entered the public eye around 5 years ago, can edit DNA with astonishing precision. The technique has two main components: a DNA-snipping enzyme known as Cas9, and a snippet of RNA, called Guide RNA.
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The Guide RNA targets specific parts of the DNA, basically telling Cas9 where to cut. The technique works well, but it is not without risk. Some researchers have been cautious, and this year shed some light on a not perfect safety record.
In March, Nature Methods retracted a controversial 2017 paper, in which researchers had said their CRISPR’d mice subjects had large amounts of ‘off-target mutations’, which resulted from Cas9 cutting in places it wasn’t suppose to. The journal was forced to pull the study and paper after the authors could not show that the mutations were from gene editing, or if they were pre-existing.
New research indicates issues when CRISPR missed it’s target, but also when it hit.
Over the course of the summer, a series of papers emerged that suggested CRISPR edits could lead to cancer. In June, two studies published in Nature Medicine reported the possible link. CRISPR is much harder to use in healthy cells that in cells that lack the protein p53 – p53 being a key tumor suppressing protein. The findings suggested that CRISPR might pick tumor-prone cells in particular.
“If you put this back into a patient, there’s a certain risk that these cells tht have a p53 deficiency might cause cancer in the long term” – Bernhard Schmierer, Senior author & researcher at Karolinska Institute in Sweden
In July, a paper in Nature Biotechnology published a paper by UK geneticists that CRISPR had sometimes swapped, flipper or even removed large chunks of DNA at target sites. These big changes could be issues if they happen to one of hundreds of different cancer-causing genes.
The findings have highlighted possible issues – and not just when CRISPR missed it’s target, but when it was able to hit it as well. Gaétan Burgio, a geneticist at the Australian National University who was not involved in any of the studies published, is confident that the problems can be overcome. He’s also certain that there will be more of these troubling findings coming to light.
“There are a lot of things we don’t know about CRISPR systems…So I would expect more of this in the future”