2018-07-16

More Bad News for CRISPR

STAT: Potential DNA damage from CRISPR has been ‘seriously underestimated,’ study finds
From the earliest days of the CRISPR-Cas9 era, scientists have known that the first step in how it edits genomes — snipping DNA — creates an unholy mess: Cellular repairmen frantically try to fix the cuts by throwing random chunks of DNA into the breach and deleting other random bits. Research published on Monday suggests that’s only the tip of a Titanic-sized iceberg: CRISPR-Cas9 can cause significantly greater genetic havoc than experts thought, the study concludes, perhaps enough to threaten the health of patients who would one day receive CRISPR-based therapy.

The results come hard on the heels of two studies that identified a related issue: Some CRISPR’d cells might be missing a key anti-cancer mechanism and therefore be able to initiate tumors.

The DNA damage found in the new study included deletions of thousands of DNA bases, including at spots far from the edit. Some of the deletions can silence genes that should be active and activate genes that should be silent, including cancer-causing genes.
I do not know much about genetics, but I've it proposed that the lots of "empty" parts of DNA might matter in the same way it matters in computer code. Empty space matters if there's a command such as "skip 20 lines" or if there's a code that says "check if line 14,304 equals A, if yes then X, if not then Y." Cutting DNA would screw up the entire system.
The possibility of adverse consequences from CRISPR’d cells has caused some company officials to argue that if, say, their therapy cures a child of a devastating disease, but increases her risk of cancer, that might be an acceptable trade-off.

That argument may well prevail. In 2003, however, when a boy in a gene therapy trial in France developed leukemia because the repair gene landed in the wrong place in his genome and activated a cancer-causing gene, it shut down gene therapy development on both sides of the Atlantic for years.
This could quickly become a big issue for gene therapies as social mood darkens. Technology is often a casualty during declining mood, particularly if it messes with Nature.

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