PPL PRODUCES WORLD'S FIRST CLONED PIGS
A major step towards successful production of Xeno
organs for human use
PPL Therapeutics Plc is pleased to announce that on 5th March 2000, five
piglets, all healthy, were born as a result of nuclear transfer (cloning)
using adult cells. This is the first time cloned pigs have been
successfully produced from adult cells. DNA from blood samples taken from
the piglets was shown in independent tests to be identical to DNA from the
cells used to produce the piglets but clearly different from DNA taken
from the surrogate mother. The DNA tests were carried out by Celera-AgGEN
on coded samples. The cell samples had been provided to the testing
company before the piglets were born.
The successful cloning of these pigs is a major step in achieving PPL's
xenograft objectives. It opens the door to making modified pigs whose
organs and cells can be successfully transplanted into humans; the only
near term solution to solving the worldwide organ shortage crisis. Pigs
are the preferred species for xenotransplantation on scientific and
ethical grounds. Clinical trials could start in as little as four years
and analysts believe the market could be worth $6 billion for solid organs
alone, with as much again possible from cellular therapies, eg.
transplantable cells that produce insulin for treatment of diabetes.
Nuclear transfer in pigs has proved to be more difficult than for other
livestock, in part because pig reproductive biology is inherently more
intractable, and partly because pigs need a minimum number of viable
foetuses to maintain pregnancy, whereas sheep and cows, for example, need
only one.
The method used to produce the five female piglets, to be named Millie,
Christa, Alexis, Carrel and Dotcom, was different from that used to
produce "Dolly" in that it used additional inventive steps for which a
patent application has been filed. The work was carried out by PPL's US
staff in Blacksburg, Virginia, partly supported by an ATP Award from the
US Government's National Institute of Standards and Technology. This award
has as its objective the production of a "knock-out" pig, i.e. a pig which
has a specific gene inactivated. The ability to clone pigs is the first
essential step in achieving this objective.
The gene to be inactivated is alpha 1-3 gal transferase. This gene is
responsible for adding to pig cells a particular sugar group recognised by
the human immune system as foreign and which therefore triggers an immune
response leading to hyperacute rejection in humans of the transplanted
organ. PPL has already achieved the required targeted gene knock out in
pig cells, using the same patented technology that led to the lambs Cupid
and Diana.
Alan Colman, PPL's Research Director said:
"In continuing its proud tradition of achieving world firsts - first to
clone an adult mammal, Dolly (with the Roslin Institute), first to achieve
gene knock-out in livestock, and now first to clone pigs - PPL has built
up the technical expertise and intellectual property to be the first to
produce the type of pig which should become the industry standard for
xenotransplantation - a pig lacking the alpha 1-3 gal transferase gene."
Dave Ayares, VP Research at PPL Inc, said:
"We are delighted. Earlier ultrasonic scans suggested we might have three
or possibly four developing fetuses. The fifth was a bit of a surprise but
it is easy in pigs for a fetus to hide beneath another during ultrasound
scans. Solving nuclear transfer in pigs was quite a challenge, so ultimate
success is all the more rewarding. This was a great team effort by all at
PPL."
In addition to today's announcement, PPL's xenograft programme has already
made considerable progress in that potential solutions for all the four
known causes of xenograft rejection have been devised and shown to work in
cell based experiments. In addition to the gene knock-out discussed above
that is required to prevent hyperacute rejection, three more genes will
need to be introduced into pigs or into pig cells to control the two
causes of delayed xenograft rejection. Finally, potential transplant
patients will be given a transfusion containing modified cells, taken from
the carefully selected strain of pigs that will supply the organs, which
will "tolerise" the patient and thereby reduce long term rejection.
Ron James, Managing Director of PPL, said:
"We are unaware of any other group that has as comprehensive an approach
to xenotransplantation as PPL. All the known technical hurdles have been
overcome. It is now a case of combining the various strategies into one
male and one female pig, and breeding from these."
"An end to the chronic organ shortage is now in sight. The next step for
PPL is to repeat the pig cloning experiment to produce knock-out pigs. We
are looking at various ways to fund our xenograft programme, including
discussions with potential marketing partners."
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NewsFor more information contact:
PPL Therapeutics plc:
April D'Arcy
Tel: +44 (0) 131 440 4777
