Studies Find CRISPR May Increase Cancer Risk, But That's Not All There Is To The Story

CRISPR's not dead yet. CI Photos/Shutterstock

Robin Andrews 12 Jun 2018, 16:37

Although still in the proof-of-concept phase, the gene-editing tool CRISPR-Cas 9 –  an ancient bacterial defense mechanism co-opted to our own needs – will almost certainly change the world.

There’s much we need to learn about it, though, and a new Nature Medicine study highlights that fact. Led by Novartis Institutes for Biomedical Research in Cambridge, a pharmaceutical company based in Switzerland, their work with CRISPR found that it tends to kill off embryonic stem cells, those that can differentiate into any cell type in the human body.

It appears that the gene-editing techniques double-strand breaks – snips in both strands of DNA’s double helix – are, as the authors of the paper term it, “toxic,” which leads to a die-off of most stem cells. They report that this effect was less apparent in previous studies because the techniques’ efficiency was lower.

What’s particularly concerning is that in the remaining stem cells can contain a malfunctioning gene named p53. When this gene is working, it helps cells to deal with stressors, and instructs damaged cells to die or stop replicating, which makes it a powerful anti-cancer gene. As a new, separate study focusing on p53 elucidates, a malfunction of this gene causes at least half of all cancers.

The problem is that p53 reduces the efficiency of CRISPR gene-editing. CRISPR is inadvertently going for cells without a functioning p53 gene because it’s better at fixing them, but this essentially leaves behind edited cells with cancer-prone mutations in them.

This study therefore suggests that there’s a risk that the CRISPR editing of embryonic stem cells may up the risk of cancer down the line, but precisely what that risk may be remains unclear.

As it happens, yet another CRISPR/p53 Nature Medicine paper by a different team – this time led by Stockholm’s Karolinska Institute – has also been published this week. Although these researchers were probing cells found in the human retina, the outcome was the same as the aforementioned work: CRISPR leads to a selection of cells with a dysfunctional p53 gene.

Dr Alena Pance, a senior staff scientist at the Wellcome Trust Sanger Institute – and who wasn’t involved in the latter study – explained to Science Media Centre that these results were certainly important, but there's a huge caveat.

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