WORLD’S FIRST CLONED DOUBLE KNOCK-OUT PIGS
LACK BOTH COPIES OF GENE INVOLVED IN HYPERACUTE REJECTION IN HUMANS
PPL Therapeutics Plc ("PPL"), one of the leading biopharmaceutical companies in
the application of transgenic technologies is pleased to announce it has
produced the World’s first double gene ‘knock-out’ piglets which were born as a
result of using PPL’s proprietary gene targeting technology and nuclear transfer
(cloning). Earlier this year PPL announced the birth of pigs in which a single
copy of the alpha 1,3 galactosyl transferase (GT) gene had been knocked out -
the single ‘knock-out’ pigs. This development is an extension of that work.
Four healthy piglets were born at PPL Therapeutics Inc, USA on 25 July, 2002 and
continue to do well. A fifth piglet died shortly after birth of unknown causes.
The gene that has been double ‘knocked-out’ in these pigs is responsible for
making an enzyme that adds a sugar to the surface of pig cells which is
recognised by the human immune system as foreign. This pig sugar (alpha 1,3
galactose) triggers an immune response in the human patient, leading to
hyperacute rejection of the transplanted organ or cell within minutes. The
ability to delete or ‘knock-out’ both copies of the gene, therefore, provides a
vital step in producing pigs with organs and cells which can be used in humans.
Because both copies of the gene have been inactivated, tissues from these pigs
have been shown to be completely devoid of the pig sugar that cause the
hyperacute rejection to take place.
As announced earlier in the year, PPL is in the process of ‘spinning out’ its
regenerative medicine programme (xenografts and stem cells), of which the
knock-out pig programme is part, in order to focus its resources on its lead
protein products, recAAT for hereditary emphysema, Fibrin 1, and BSSL. It is
also the Board’s belief that the resources required to bring a product to market
in the area of regenerative medicine will be significant and beyond the current
resources of PPL. The announcement today, however, recognises another key
milestone for PPL in the area of xenotransplantation and demonstrates the
company’s leading-edge position in this rapidly developing field. The company
intends to have completed the spin-out by the end of the year.
As part of PPL’s ongoing collaboration with the University of Pittsburgh’s
Thomas E. Starzl Transplant Institute, organs and cells from these double
knock-out pigs will be used in pivotal transplantation studies aimed at testing
for elimination of hyperacute rejection and long term survival of these
The ‘knock-out’ work was carried out by PPL Therapeutics Inc, PPL’s US
subsidiary located in Blacksburg, Virginia, and was partly supported by an ATP
Grant from the US Government’s National Institute of Standards and Technology (NIST).
In addition to these double knock-out pigs, the company has generated more than
60 male and female single gene GT knock-out pigs since the first litter was born
in December 2001, demonstrating that this technology is now a reliable and
reproducible tool for making very precise genetic changes in these animals.
David Ayares, COO and VP of Research at PPL Therapeutics Inc said:
"This advance brings us closer to the promise of a potential solution to the
world-wide shortage of organs and cells for transplantation."
Geoff Cook, Chief Executive Officer said:
"This is an important step for PPL demonstrating our leading position in this
exciting area. The news will support our efforts in spinning out PPL’s
regenerative medicine business, that will then enable us to focus on our core
For more information contact:
PPL Therapeutics plc:
Tel +44 (0)131 440 4777
Financial PR Enquiries:
Tel +44 (0)20 7796 4133
Notes to Editors:
PPL Therapeutics is a biopharmaceutical company which is one of the world’s
leaders in the application of transgenic animal technologies to the development
and production of human proteins for therapeutic and nutritional applications.
PPL has a broad pipeline of diverse protein products including AAT, the
Company’s lead product, which is currently in Phase II clinical trials for
cystic fibrosis. AAT is also under development for the treatment of congenital
deficiency. PPL’s other lead products are fibrinogen and bile salt stimulated
Transgenic production of human proteins involves the introduction of copies of
human DNA into the genetic material of another species. The resulting transgenic
animals express the human gene product (protein) in the mammary gland allowing
its collection and purification during lactation. The technique offers the
opportunity to produce human proteins economically and in potentially unlimited
PPL has a world wide exclusive licence from the Roslin Institute to use the
Institute’s intellectual property relating to nuclear transfer (cloning) in the
field of production of proteins for pharmaceutical and nutraceutical use in the
milk of ruminant livestock and rabbits.