Almost half of all cancers carry the same broken gene, and for years, drugs meant to fix it have come up short.
Now researchers at UC Berkeley, UCSF and the Gladstone Institutes have tried something completely different. Instead of repairing the broken gene, their new CRISPR tool hunts down the cells carrying it and shreds their DNA until the cell dies.
In a healthy body, a protein called p53 works like a safety switch. It tells damaged cells to stop growing or to quietly self-destruct before they turn into a tumor. When p53 breaks, that switch stops working and cancer cells start to multiply unchecked. It's broken in roughly half of all cancers, one of the most common failures behind the disease.
Some cancer drugs work by shutting down a gene that is stuck in the on position. A broken p53 is the opposite problem, only tougher. The useful part is switched off, and there's no easy chemical way to flip it back on. Scientists have chased that goal for years, with no standard treatment to show for it. Researchers even call cancers like these "undruggable."
Destroying cells instead of fixing them
So the team stopped trying to fix the gene at all. CRISPR is famous now as a gene-editing tool, but in nature it began as a defense system that destroys invading viruses by cutting up their genetic material.
The researchers pointed that destroy mode at cancer instead, building a tool that searches for cells carrying the specific cancer mutation and, the moment it finds one, cuts that cell's DNA to pieces until the cell dies.
Jingkun Zeng, the study's first author, said he "wanted to destroy abnormal cells, precisely and safely." That is the opposite of most gene-editing work, which usually tries to repair a gene or switch it off. The team published its results in the journal Nature.
It worked in lab tests. The tool destroyed cells carrying the cancer mutation while leaving cells with the normal version of the gene almost completely alone. It can also be reprogrammed to go after other mutations, not just this one, which could make it useful well beyond a single kind of cancer.
But this is early, and a long way from a treatment. So far the tool has been tested on cells in the lab and in mice, never in people.
To reach the tumors in the mice, the team wrapped its instructions in tiny fat bubbles. Those early results looked promising but modest. The biggest hurdle now is getting the tool into enough of the right cells safely, which the team calls its next challenge. There's no treatment yet.
Nature CRISPR cancer study, UCSF study summary, CRISPR Medicine mouse-test analysis
