2019-01-01_Discover

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January/February 2019^ DISCOVER^37


FROM TOP: MONICA SCHROEDER/SCIENCE SOURCE; SALK INSTITUTE; HANNAH GRUNWALD


CRISPR’s New Target


The CRISPR field has mainly focused on
editing DNA, but many diseases could be
treated by altering RNA, the molecule
that carries out DNA’s instructions.
Unlike DNA edits, RNA changes
aren’t permanent, so targeting the
messenger molecule might mean
fewer safety risks.
In March in the journal Cell,
researchers at the Salk Institute unveiled
a new CRISPR enzyme that does just that.

Researchers conducted their initial tests in
cells from patients with a particular type
of dementia where proteins called tau
build up to unhealthy levels; the new
CRISPR system successfully rebalanced
tau levels.
Its name, CasRx, hints at its future
in medicine, according to lead
investigator Patrick Hsu. “It’s absolutely
inspired by our vision of its therapeutic
potential,” he says.

at the Karolinska Institute in
Sweden, and a senior author of
one of the studies.
And in July, U.K. geneticists
reported in Nature Biotechnology
that CRISPR sometimes
removed, ipped or swapped
surprisingly large chunks of
DNA at on-target sites. These
large-scale rearrangements could
be an issue if they involve one
of hundreds of potential cancer-
causing genes.
The new indings highlight
possible problems not just when
CRISPR misses its mark, but also
when it hits its target.
Gaétan Burgio, a geneticist at
Australian National University
who was not involved in the

aforementioned studies, is conident
that researchers can overcome the
problem, just as he’s conident there
will be more indings like these to

come. “There are a lot of things
we don’t know about the CRISPR
system,” he says. “So I would expect
more of this in the future.”

Mammalian Gene Drive Stuck in First Gear


So-called gene drives, which use
genetic engineering to preferentially
pass on specific genes to offspring,
can doom a species. Some
controversial proposals have called
for using them on mosquitoes to
eliminate malaria, or to rid islands of
invasive rodents. While CRISPR-based
gene drives have shown promise in
insects, no one had deployed one in
mammals — until now.
In July, researchers announced
the milestone in mice, although the
results scuttled optimism for a quick
pest-control solution. To prove how

this might work one day, a team at
the University of California, San Diego,
attempted to spread a mutation that
would turn the rodents white. But
only females copied over the change,
and sometimes with errors.
“It is much easier in mosquitoes
and flies,” says Australian National
University’s Gaétan Burgio, who
was not involved with the research.
Ultimately, he says, given technical
hurdles and biological differences
specific to mammals, he’s skeptical
a gene drive will work on them in
the wild anytime soon.

CRISPR-Cas9
Once the Cas9 enzyme and guide RNA enter
a cell, the RNA directs Cas9 to a specific
spot on the organism’s genome. There,
the enzyme can cut the targeted
sequence of genes.

Guide RNA

Cas9

Section of guide RNA
that matches genome

Targeted genome
to be cut

CRISPR failed to
turn all of these
pups white.

CasRx (pink) in
human cells (gray)
Free download pdf