Scientists have used gene editing to reprogramme a signal that normally promotes tumour growth into one that shrinks it instead. In a study published in Nature Methods, a team from the First Affiliated Hospital of Shenzhen University, China, showed how they could stop the growth of cancer in cells by modifying part of the CRISPR–Cas9 system.
When mice carrying these modified genes were tested, scientists found their tumours were far smaller than those seen in control animals.
CRISPR-Cas9 is a gene editing platform that is currently being looked at as a means of providing treatments for diseases by targeting cells. Cas9 is an enzyme that cuts a double DNA strand at a point, while CRISPR is a chemical messenger. The latter can guide Cas9 so it binds with a specific part of the genome – meaning scientists can disrupt, edit or insert a new sequence to make it have a new function.
In their study, the team looked used this gene editing technique to target eukaryotic cells. They receive signals to regulate their gene expression. This is what scientists targeted with CRISPR-Cas9.
Scientists manipulated the signalling pathway to regulate gene expression at the site. They modified the component so it became activated by a signal that normally promotes tumour growth. They then brought in two tumour suppressor genes, meaning cancer cells would not grow.
In experiments with mice, they found their technique had an anticancer effect. Cancer cells were injected into mice and after several days, tumours developed. Treated mice were found to have "dramatically smaller" tumours than the control mice.
A long time before patients see benefits
Commenting on the study, Andrew Sharrocks, Professor of Molecular Biology at the University of Manchester, said: "CRISPR technology is a new method for genome editing. These authors report a clever use of this technology to control cancer growth in mice by manipulating the expression of cancer causing genes.
"The really interesting aspect is that they use a system which responds to signals created by the cancer cells themselves as they grow. This then causes specific genes to switch on or off which result in elimination of the cancer. This is an interesting approach and could have many applications in studying cancer biology in mouse models. However at this stage, it is difficult to envisage how this might be applied to treating cancer in humans."
Chris Lord, from the Institute of Cancer Research, added: "It's an interesting idea: using the fundamental nature of a tumour cell to activate a 'suicide' program. The key to translating this technique into the clinic will be to see how specific to the tumour cell the CRISPR activation will be and how specific, in terms of genes, the CRISPR mediated gene cutting will be.
"These are essentially the same two issues you have with all cancer treatments – how specific for the tumour cell and how specific for the target. There is a lot more research needed before this technique can be tested on humans, so it will be a long time before patients see benefit from this advancing technology."