Monday, June 11, 2018

CRISPR-edited cells might cause cancer, two studies find


E
diting cells’ genomes with CRISPR-Cas9 might increase the risk that the altered cells, intended to treat disease, will trigger cancer, two studies published on Monday warn — a potential game-changer for the companies developing CRISPR-based therapies.
In the studies, published in Nature Medicine, scientists found that cells whose genomes are successfully edited by CRISPR-Cas9 have the potential to seed tumors inside a patient. That could make some CRISPR’d cells ticking time bombs, according to researchers from Sweden’s Karolinska Institute and, separately, Novartis.
Another leading CRISPR scientist, who asked not to be named because of involvement with genome-editing companies, called the new data “pretty striking,” and raised concerns that a potential fatal flaw in some uses of CRISPR had “been missed.”

The Karolinska and Novartis groups tested CRISPR on different kinds of human cells — retinal cells and pluripotent stem cells, respectively. But they found essentially the same phenomenon. Standard CRISPR-Cas9 works by cutting both strands of the DNA double helix. That injury causes a cell to activate a biochemical first-aid kit orchestrated by a gene called p53, which either mends the DNA break or makes the cell self-destruct.CRISPR-edited cells might cause cancer, two studies find
The flip side of p53 repairing CRISPR edits, or killing cells that accept the edits, is that cells that survive with the edits do so precisely because they have a dysfunctional p53 and therefore lack this fix-it-or-kill-it mechanism.
The reason why that could be a problem is that p53 dysfunction can cause cancer. And not just occasionally. P53 mutations are responsible for nearly half of ovarian cancers; 43 percent of colorectal cancers; 38 percent of lung cancers; nearly one-third of pancreatic, stomach, and liver cancers; and one-quarter of breast cancers, among others.
The p53 finding doesn’t mean CRISPR is toast. For one thing, “the two papers present preliminary results,” biochemist Bernhard Schmierer of the Karolinska, co-leader of its study, told STAT. “It is unclear if the findings translate into cells actually used in current clinical studies.”

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