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Precision gene editing tool could increase cancer risk in patients

Scientists urge caution before leaping ahead with gene-editing treatments.

A powerful gene editing tool with the potential to revolutionise medicine could also increase the risk of cancer, scientists have warned.

The “molecular scissors” technology known as CRISPR-Cas9 is capable of making highly precise changes to DNA.

It has already transformed laboratory research into inherited diseases, stem cells and embryonic development.

In future, it could also form the basis of personalised treatments for genetic disorders such as cystic fibrosis and muscular dystrophy, and cancer immunotherapy.

But there is a catch, according to a new study by researchers from Cambridge University and the Karolinska Institute in Sweden.

Like with any medical treatment, there are always side effects or potential harm and this should be balanced against the benefits of the treatment Professor Jussi Taipale

CRISPR-Cas9 appears to work most effectively on cells lacking a mechanism that protects them from DNA damage.

As a result it is likely to pick out abnormal cells that can sow the seeds of cancer, the research suggests.

Patients given DNA-editing treatment could end up with larger numbers of these potentially dangerous cells ticking like time bombs in their organs or blood stream.

Lead scientist Professor Jussi Taipale, from Cambridge University’s Department of Biochemistry, said: “CRISPR-Cas9 is a very promising biological tool, both for research purposes and for potential life-saving medical treatments, and so has understandably led to great excitement within the scientific community.

“We don’t want to sound alarmist, and are not saying that CRISPR-Cas9 is bad or dangerous.

“This is clearly going to be a major tool for use in medicine, so it’s important to pay attention to potential safety concerns.

“Like with any medical treatment, there are always side effects or potential harm and this should be balanced against the benefits of the treatment.”

CRISPR-Cas9 was discovered in bacteria which developed the system to defend themselves against viruses.

It works by first homing in on a precise location in the double-helix DNA molecule and then cutting both strands to snip away a faulty section. The defective DNA can then be replaced.

The research showed how in normal cells, slicing up DNA using CRISPR-Cas9 triggered activation of an alarm signal anti-cancer protein called p53.

This in turn led to rapid repair of the damage, making editing more difficult.

Cells lacking the p53 pathway were much more susceptible to CRISPR-Cas9 editing, but also more at risk of turning cancerous.

The pathway is absent in around half of all tumour cells.

Co-author Dr Emma Haapaniemi, from the Karolinska Institute, said: “We managed to edit cancer cells easily, but when we tried to edit normal, healthy cells, very little happened.”

The scientists found that the process led to the “strong selection” of cells unable to generate p53.

Artificially reducing p53 activity made it easier to edit cells with the cancer-protective pathway, but raised the risk of tumour-triggering mutations.

Prof Taipale said: “Although we don’t yet understand the mechanisms behind the activation of p53, we believe that researchers need to be aware of the potential risks when developing new treatments.

“This is why we decided to publish our findings as soon as we discovered that cells edited with CRISPR-Cas9 can go on to become cancerous.”

The research appears in the latest issue of the journal Nature Medicine alongside similar results independently reported by US scientists from the Novartis Research Institute in Boston.

Genetics expert Professor Darren Griffin, from the University of Kent, said: “Almost any treatment that has the power to do good has the power to do harm and this finding should be considered in this broader context.

“As we learn more about the CRISPR-Cas9 system and how it can be used, this study will inevitably be considered a significant finding.”

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