14 | NewScientist | 8 September 2018NEWS & TECHNOLOGY
Chelsea WhyteCRISPR gene-editing has been
used to improve muscle function
in dogs with a condition similar to
Duchenne muscular dystrophy
(DMD) – and the technique might
one day lead to a treatment for
humans. The study represents the
first use of CRISPR gene-editing in
a living large animal.
People with DMD have a genetic
mutation that makes them unable
to produce dystrophin, a protein
that maintains muscle structure
and function. The condition canresult in heart or lung failure.
In 2010, Richard Piercy at the
Royal Veterinary College in
London and his colleagues
identified the same mutation in a
Cavalier King Charles spaniel that
was brought into the veterinary
hospital showing muscle
weakness. They found relatives
of that dog and bred them with
beagles. Three of the resulting
pups have now been used to testa potential treatment for DMD.
Today there is only one
approved DMD treatment to
elevate dystrophin levels. In
clinical trials, this drug treatment
had modest effects: people taking
it could produce dystrophin but
only at about 0.4 per cent the
levels seen in healthy individuals.
The gene-editing treatment has
been able to restore up to 92 per
cent of the dystrophin expression
in the beagles’ heart tissue, 58 per
cent in the diaphragm and 64 per
cent in the biceps.
This method relies on CRISPR
Cas9, a genome editing enzyme
that cuts a cell’s DNA in a specific
spot, guided there by RNA.
The team injected a virus
carrying CRISPR and its RNA
molecular guide into the skeletal
muscle and heart tissue of two one-
month old beagles with the DMD
mutation. It is the first time CRISPR
has been used in live animals of
such a large size, says Eric Olson
at the University of Texas
Southwestern Medical Center.
Six weeks later, they analysed the
dogs’ muscles and sequenced
their genomes before comparing
them with a dog with the same
mutation, and a healthy dog.“We looked through the
microscope and it was jaw-
dropping,” says Olson. “Virtually
all of the muscle fibres showed
high levels of dystrophin
underlying every membrane.
We were exuberant.”
However, he says it is not
known whether the treatment
would have such dramatic effects
in the human version of the
condition (Science, doi.org/ctgz).
Melissa Spencer at the
University of California, Los
Angeles, says the results are a
great first step towards a
treatment, but she cautions thatthey require more safety testing.
“The Cas9 protein expresses
for a long time, so the immune
system could attack it. We need a
better assessment of the immune
response, and we also need to be
sure CRISPR isn’t cutting off-
target,” Spencer says.
Recently, concerns have been
raised that CRISPR does indeed
cut off-target – snipping up DNA
where it isn’t supposed to. Olson
says they didn’t see evidence that
this was happening in the dogs,
and blood tests were normal after
the treatment.
Piercy adds that he hopes the
treatment could lead to a routine
therapy for dogs with muscle
disease, as well. ■CRISPR helps dogs’
muscle disease
RVC“ Virtually all of the muscle
fibres showed high levels
of dystrophin. We were
exuberant”
THE cleaner wrasse has become the
first fish to pass the mirror test – a
classic experiment used to gauge
self-awareness in animals.
Until now, only relatively intelligent
animals – such as apes and elephants –
have passed the test, which shows
whether an individual can recognise
itself. To see if fish may also be
self-aware, Masanori Kohda at OsakaFish passes
mirror test for
first time
City University, Japan, and his
colleagues put 10 wild cleaner wrasses
in individual tanks with a mirror.
During the first few days, seven
of the fish attacked their mirror
images. But these fish then began
to dash towards the mirror and
dance – unusual behaviours that
have never been observed before.
The team put a coloured gel onto
the heads of eight of these fish, in
positions that could be seen only
using the mirror. Seven of the fish
spent significantly more time in front
of the mirror in poses that let them
observe the mark on their head. Someeven tried to scrape it off (bioRxiv,
doi.org/cthm). According to the team,
this means cleaner wrasses are as
successful at recognising themselves
in a mirror as elephants.
However, Gordon Gallup of the
University at Albany, New York, who
invented the mirror test, is not
convinced. Cleaner wrasses eat
parasites living on other fish. These
wrasses probably mistook the marks
for parasites on the skin of other fish,
Gallup says. Yvaine Ye ■See page 10 and page 28 for more on
self-awareness and intelligenceSome of these dogs have a genetic
muscle condition – but which?Cleaner wrasse are only about the
size of a human fingerHELMUT CORNELI/ALAMY