14 | New Scientist | 19 February 2022
SEVERAL groups are vying to be
the first to transplant organs from
genetically modified pigs into
people as part of a clinical trial.
One of the contenders is a team in
China that last year was the first to
complete a human trial of CRISPR
genome-edited pig skin grafts.
“We plan to do heart or liver
xenotransplants within 2022, but
we do not have a specific timetable
at this moment,” says Lijin Zou
at the First Affiliated Hospital of
Nanchang University in China.
“We are completing all
the technical and medical
preparations, including the
preparation of surgeons and
the ICU team for solid organ
xenotransplants,” he says.
“We are in the middle of seeking
all the necessary approvals.”
Teams around the world are
genetically modifying pigs to
make their organs less likely to be
rejected by the human immune
system. Zou’s team has removed
three genes from a strain of
miniature pig and added eight
human genes. The changes are
similar to those made to the pig
whose heart was transplanted into
David Bennett at the University of
Maryland School of Medicine on
7 January. This transplant, which
made headlines worldwide, was
done as a last resort rather than as
part of a trial. The pig came from a
line created by US firm Revivicor.
Last year, Zou’s team carried out
a clinical trial involving 16 people
with burns. With severe burns, it
is often necessary to temporarily
cover the wounds with skin
from human cadavers or pigs
to prevent infection and the loss
of fluid and to help prepare the
site for a skin graft taken from
elsewhere on the body.In the trial, each person had
a “Xeno X” skin graft from the
modified pigs placed alongside a
material derived from unmodified
pigs. No drugs were given to stop
their bodies rejecting the grafts.
The material from unmodified
pigs never linked up with blood
vessels in the human tissue to
get a blood supply, and lasted just
eight days. Skin from human
cadavers also typically lasts eight
days when used in this way.
The skin from the modified pigs
quickly developed a blood supply.
The grafts did start to be rejected,
as expected, but survived for25 days, after which they were
removed. None of the people
treated had any adverse reactions
or developed infections (medRxiv,
doi.org/hgmp).
“Our unprecedented work
demonstrates that the Xeno X skin
could be an effective treatment for
severe burns, particularly when
human cadaveric skin is in short
supply,” says Zou.
Other researchers say thatthe results are encouraging.
“The availability of a modified
xenograft that lasts longer could
be of significant benefit to patients
with large and deep wounds,”
says Adam Singer at Stony Brook
University in New York.
Zou says his team will now
expand the trial and include
people with life-threatening
burns. The team is also making
further genetic changes to pigs
to improve the skin. It might
eventually be possible to create
pigs whose skin looks and
functions just like human skin for
long-term replacement, he says.
The team also hopes to get the
go-ahead to transplant organs
from modified pigs into people
about to die while waiting for a
human organ. Initially, the pig
organs would be a temporary
measure, to be replaced by ones
from humans. The team is likely
to start with heart transplants.
“The Chinese project looks
promising,” says Herbert Haller
at the Trauma Hospital Berlin
in Germany. But long-term trials
need to be done, he says.
Several groups in the US are also
awaiting approval to commence
such trials. Muhammad
Mohiuddin at the Universityof Maryland School of Medicine,
whose team transplanted the
Revivicor pig heart into Bennett,
says his team is seeking approval
for a clinical trial from the US Food
and Drug Administration (FDA).
“However, the FDA wants us to
do further non-human primate
studies before they give us this
permission,” says Mohiuddin.
Hearts from normal-sized pigs
can grow too large after being
transplanted. In the pig line that
provided the heart for Bennett,
Revivicor has deleted a gene for a
growth hormone receptor to try to
prevent this. Zou thinks his team’s
use of miniature pigs will prove
to be an advantage in this regard.
In 2021, two teams temporarily
transplanted Revivicor pig kidneys
into people diagnosed as brain
dead, and at least one of the teams
aims to start clinical trials soon.
“We are very hopeful that we would
be able to implement a phase I trial
later this year,” said Jayme Locke
at the University of Alabama at
Birmingham at a press conference
on 20 January. “We do have a herd
of pigs that would be ready.”
Also in the race is a US company
called eGenesis that has, in
collaboration with a Chinese firm
called Qihan Biotech, created
pigs with even more extensive
changes than those modified
by Zou’s team and Revivicor.
“We are meeting with the
FDA in the middle of this year
for both our kidney and [insulin-
producing] islet cell programmes,”
says a spokesperson for eGenesis.
“With their guidance, we will
move our programmes into the
clinic as quickly as possible.”
Neither Qihan Biotech nor
a US xenotransplant company
called Makana Therapeutics,
part of bioengineering firm
Recombinetics, responded
to questions about their plans
for clinical trials. ❚“ It might eventually be
possible to create pigs
whose skin looks and
functions like human skin”XenotransplantationPE
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YPig organ trials may start soon
After completing a human trial of modified pig skin grafts last year, a team in China
hopes to start the first pig organ transplant trial, reports Michael Le PagePigs could be genetically
engineered to provide
transplant organsNews