Studies Suggest CRISPR Gene Editing May Cause Cancer

Studies Suggest CRISPR Gene Editing May Cause Cancer

The CRISPR gene editing tool has attracted considerable interest due to the ease at which it can be used to edit troublesome genes and eradicate a wide range of diseases. CRISPR, coupled with its Cas9 enzyme component, allows genes to be altered or totally removed. While the tool has shown incredible promise and has even been used on humans with positive results, it is not without its problems.

CRISPR can make highly specific edits to genes, but there is still potential for off-target effects that could prove catastrophic for patients. Now, a new potential flaw has been discovered. Two separate studies suggest while CRISPR can make genome edits that will benefit patients, the technique can also increase the risk of patients developing cancer.

Both studies – conducted by Novartis and the Karolinska Institute in Sweden/University of Helsinki in Finland – were recently published in the journal Nature Medicine. Both studies show that cells that have had their genomes edited with CRISPR-Cas9 could trigger the formation of tumors when those cells are introduced into patients.

The studies have shown that in a laboratory setting, use of CRISPR-Cas9 on cells activates a protein called p53 which is used to repair damage to the DNA. The protein has also been shown to prevent the formation of tumors. A lack of p53, or an inability to synthesize the protein, can contribute to the rapid and uncontrollable growth of cells which can become cancerous.

P53 also reduces the efficiency of CRISPR-Cas9 genome editing; therefore, if scientists select the cells where editing has had the intended outcome, it is likely that they will also be selecting cells without p53 or cells that lack the ability to activate p53.

“If transplanted into a patient, as in gene therapy for inherited diseases, such cells could give rise to cancer, raising concerns for the safety of CRISPR-based gene therapies,” said Dr Emma Haapaniemi, first author of the Karolinska Institutet study. Similar conclusions were drawn by researchers at Novartis.

These studies do not signal the end of the road for CRISPR. They just show that further research is required to determine the negative effects from CRISPR gene editing. Further, the studies only demonstrate potentially negative effects with Cas9, and not other CRISPR enzymes such as Cpf1. The problems may not occur if genes are totally removed, as the study only shows p53 arise when genes are edited.

The Karolinska Institutet study – CRISPR/Cas9-genome editing induces a p53-mediated DNA damage response – was published in Nature Medicine on June 11, 2018 – doi: 10.1038/s41591-018-0049-z

The Novartis study – p53 inhibits CRISPR–Cas9 engineering in human pluripotent stem cells – was published in Nature Medicine on the same date – doi: 10.1038/s41591-018-0050-6

Leave a Reply