release, Tuesday 14th March 2000
David Ayares, VP of Research and Development
|Dr Ron James,
PPL Therapeutics plc
Telephone: 0131 440 4777
PPL THERAPEUTICS INC
PPL PRODUCES WORLDS FIRST CLONED PIGS
A major step towards successful production of
Blacksburg, VA PPL Therapeutics Inc 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 PPLs 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 fetuses 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 PPLs US staff in Blacksburg, Virginia, partly supported by an ATP Award from the US Governments 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 recognized 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, PPLs 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 of 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 our ultimate success was all the more rewarding. This was a great team effort by all at PPL."
In addition to todays announcement, PPLs xenograft program 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 "tolerize" 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 program, including discussions with potential marketing partners."
Notes to Editors