CRISPR-Cas9: Cure or Carcinogen?

CRISPR-Cas9 may increase the risk of cancer in certain cells, according to a recent study from the Karolinska Institute in Sweden.

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, and is a process that serves as "molecular scissors". CRISPR, along with the enzyme Cas9, makes it possible to snip out undesired bits of DNA from cells. Scientists can then control how the broken DNA repairs itself, or even replace the removed DNA with a preferred sequence. This process holds the potential to cure genetic conditions such as cystic fibrosis.

CRISPR has been used in treating mutated genes. But now, Jussi Taipale and his team at the Karolinska Institute in Sweden tried using CRISPR on healthy cells, and the results were alarming.

“When we edited the healthy cells, an alarm went off that there is DNA damage. A protein called p53 got strongly activated and stopped the cells from dividing,” said Taipale.

P53 is a protein associated with tumor suppression. When Taipale and his team performed CRISPR on healthy cells, the p53 often resisted the treatment, making the genetic edits unsuccessful. In some cases, the healthy cells died.

Some healthy cells naturally have a deficiency of p53, making them more at risk of developing tumors and thus cancer, but also allowing them to be more responsive to CRISPR. Unfortunately, this means that when CRISPR is performed on hundreds of healthy cells, it is most successful in cells that are at greater risk for developing cancer, and may even kill off the cells that contain p53.

“If we take a large number of cells and we try to edit all of them, and the p53 gets activated, then there’s a risk that the cells which have already lost the p53 have a growth advantage,” explains Taipale, “and it could be that the normal cells that are less likely to form cancer die. Then we are left with the cells that are already on the path towards cancer.”

Fortunately, through further research it may be possible to minimise these risks. “We tested one cell type, but we cannot possibly, as a single laboratory, test all kinds of cells. So our idea was to post this out for everyone to see, so people could see that this is potentially a problem, and they can test this situation in their own context; so they can design experiments and treatment protocol so that the risk from this source could be minimized,” said Taipale.

Every treatment has its risks, and Taipale still believes CRISPR is very promising. “It has enormous potential. This direction is quite promising. I think there will be many treatments that are based on CRISPR or some related technologies.”