A new research revealed that the CRISPR–Cas9 genome editing technique may increase cancer risk

Genome editing is a technology that genetic material can be added, removed, or altered at particular locations in the genome. CRISPR-Cas9 is short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9. This system is faster, cheaper, more accurate, and more efficient than other existing genome editing methods, so is popular with researchers.

CRISPR-Cas9 is a molecular machine first discovered in bacteria that can be programmed to go to an exact place in the genome, where it cuts the DNA. These precise ‘molecular scissors’ can be used to correct faulty pieces of DNA and are currently being used 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 anemia.

Recently, a study entitled “CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response” was published in the journal of Nature Medicine, which found that therapeutic use of gene editing with CRISPR-Cas9 technique may inadvertently increase the risk of cancer. Researchers say that more studies are required to guarantee the safety of these ‘molecular scissors’ for gene-editing therapies.

In the study, genome editing by CRISPR–Cas9 induces a p53-mediated DNA damage response and cell cycle arrest in immortalized human retinal pigment epithelial cells, leading to a selection against cells with a functional p53 pathway. Inhibition of p53 prevents the damage response and increases the rate of homologous recombination from a donor template. These results suggest that p53 inhibition may improve the efficiency of genome editing of untransformed cells and that p53 function should be monitored when developing cell-based therapies utilizing CRISPR–Cas9.

Scientists from Karolinska Institutet and the University of Helsinki report that use of CRISPR-Cas9 in human cells in a laboratory setting can activate p53 protein, which acts as a cell’s ‘first aid kit’ for DNA breaks. Once active, p53 reduces the efficiency of CRISPR-Cas9 gene editing. Thus, cells that do not have p53 or are unable to activate it show better gene editing. Unfortunately, however, lack of p53 is also known to contribute to making cells grow uncontrollably and become cancerous.

“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, researcher and co-first author of the study. “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.”

In conclusion, CRISPR-Cas9 is a powerful tool with staggering therapeutic potential, however, like all medical treatments, CRISPR-Cas9-based therapies might have side effects. The patients and caregivers should realize this point. Through the study, future work on the mechanisms that trigger p53 in response to CRISPR-Cas9 will be critical in improving the safety of CRISPR-Cas9-based therapies.

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