Therapeutic gene editing may increase cancer risk

Using the recognized DNA-altering CRISPR-Cas9 technique to treat diseases may inadvertently increase the risk of cancer, according to a new study co-supervised by Bernhard Schmierer (Karolinska Institutet) who heads the High Throughput Genome Engineering unit at SciLifeLab. The results are published in Nature Medicine.

CRISPR-Cas9 is a molecular machine that can be programmed to find a precise place in the genome, where it cuts the DNA. The approach can be used to correct defective pieces of the genome and is currently being tested as an immunotherapeutic treatment for cancer in clinical trials in the US and China.

The current study utilizes cultured human cells to show that CRISPR-Cas9 can activate the protein p53, which responds to faulty DNA and triggers DNA repair mechanisms. Once active, p53 reduces the efficiency of CRISPR-Cas9 gene editing. Hence, using cells that lack p53 or are unable to activate it show better gene editing results.

However, the absence of p53 is also known to contribute to making cells grow uncontrollably and become cancerous. This contradiction is a clear signal that further studies are required in order to guarantee the safety of these ‘molecular scissors’ for gene-editing therapies.

Read a press release by Karolinska Institutet

Read the full paper in Nature Medicine