“Gene scissors” may increase cancer risk

According to researchers from the University of Helsinki and Karolinska Institute, gene editing using CRISPR-Cas9 may inadvertently increase cancer risk. A team in Novartis Research Institute in Boston also independently obtained similar results.

CRISPR-Cas9 can be programmed to remove and replace gene defects in the DNA. It is a promising biological tool for medical treatments, and the method is currently tested in clinical trials for cancer immunotherapy in the US and China. New trials are expected to be launched soon to treat inherited blood disorders such as sickle cell anaemia.

In two independent studies published today in the journal Nature Medicine, scientists at the Karolinska Institute, the University of Helsinki and the Novartis Research Institute in Boston report that the use of CRISPR-Cas9 may trigger a mechanism designed to protect cells from DNA damage. 

As the result, the cells which lack this mechanism, linked to protein known as p53, edit much better than normal cells. This can lead to a situation where genome edited cell populations have increased numbers of cells in which this important mechanism is missing.  

“By picking cells that have successfully repaired the damaged gene we intended to fix, we might inadvertently also pick cells without functional p53”, says Dr Emma Haapaniemi from Karolinska Institute, the first author of the other study. 

“If transplanted into a patient, as in gene therapy for inherited diseases, such cells could give rise to cancer risk, raising concerns for the safety of CRISPR-based gene therapies.”

The team found that by decreasing activity of p53 in a cell, they could be efficiently edited with CRISPR-Cas9. However, it the safety of it is uncertain. 

The research was lead by Professor Jussi Taipale from the University of Helsinki, and the University of Cambridge.

According to him, there is a lot of potential in CRISPR-Cas9 but more research is needed on its possible side effects and how they could be prevented.

“We are not saying that CRISPR-Cas9 is bad or dangerous. Like with any medical treatment, there are always side effects and potential harm from treatment, and this should be balanced against the benefits of the treatment.”

Contact information:
Emma Haapaniemi, emma.haapaniemi@ki.se
Jussi Taipale, jussi.taipale@helsinki.fi, tel. +358 504486335

Haapaniemi, E et al. CRISPR/Cas9-genome editing induces a p53-mediated DNA damage response. Nature Medicine, 11 June 2018, DOI: 10.1038/S41591-018-0049-Z.

Ihry, R et al. P53 inhibits CRISPR/CAS9 engineering in human pluripotent stem cells. Nature Medicine, 11 June 2018 .