36 DISCOVERMAGAZINE.COM
MOLEKUUL/SCIENCE SOURCEGENETICS
Researchers continue to wrangle with CRISPR while others debate
the ethics of catching criminals with public genealogy data.
BY JESSICA MCDONALD
CRISPR’s Roller Coaster Safety Ride
The genome-editing tool
CRISPR-Cas9 is revolutionizing
the ield of medicine. The
technology, which took off in
popularity among researchers
about ive years ago, can precisely
edit DNA. The system includes
two components: a DNA-cutting
enzyme, called Cas9, and a piece
of RNA, called guide RNA.A bit of guide RNA targets
a speciic chunk of DNA,
directing Cas9 exactly where in
the genome to snip. But slicing
and dicing DNA isn’t without
risks. Some researchers have been
wary from the get-go, perhaps
rightly so as details emerge about
CRISPR’s sometimes-troubling
safety record.The pro-CRISPR camp scored
a win in March, when Nature
Methods retracted a 2017 paper
that had stirred controversy.
The researchers originally said
their CRISPR-edited mice had
large numbers of so-called
off-target mutations that resulted
from Cas9 cutting at places other
than the intended location. But
the journal pulled the study
because the authors couldn’t show
if the changes came from gene
editing or if they were pre-existing
natural variations.Over the summer, however, a
series of papers looking at other
aspects of CRISPR raised the
specter of cancer. In June, two
Nature Medicine studies reported
a disturbing tendency. The gene
editor was more dificult to use
in healthy cells than in cells that
lacked a key tumor-suppressing
protein called p53. The indings
suggest CRISPR might select for
tumor-prone cells. “If you put
this back into a patient, there’s a
certain risk that these cells that
have a p53 deiciency might cause
cancer in the long term,” says
Bernhard Schmierer, a researcherThe new findings
highlight possible
problems not just
when CRISPR
misses its mark,
but also when it
hits its target.
An illustration
of CRISPR-Cas9