Open Competition - Biotechnology (October 1999)

Cloning Pigs: A Solution to Overcoming Rejection in Organs for Transplantation

Sponsor: Revivicor, Inc. (formerly PPL Therapeutics, Inc.)

• Project Performance Period: 11/1/1999 - 10/31/2002
• Total project (est.): $3,480,806.00
• Requested ATP funds: $2,000,000.00

Thousands of Americans die each year while waiting for organ transplants, primarily because of a growing shortage of organs from human donors. A promising but problematic solution is the use of pig organs and tissue. However a significant obstacle is hyperacute rejection (HAR) of the transplanted tissue, triggered when the human immune system recognizes a specific sugar molecule on the surface of pig cells and organs. Currently the impact of HAR can be reduced but not eliminated. In a three-year ATP project, PPL Therapeutics, Inc., proposes to accelerate the medical use of pig organs by genetically altering pig cells to prevent HAR. The company will "knock out" (inactivate) the pig gene that modifies the sugar molecule, which in turn activates the human immune response. This piece of the experimental work has been particularly difficult. However PPL has recently achieved success in this homologous recombination technology in a related system -- the sheep. Thus, this team is poised to be the first to successfully genetically engineer a pig cell. These genetically altered cells will then be used to clone pigs whose organs and tissues do not have any residues of this sugar. If successful, the ATP project is expected to reduce the risk of crucial follow-on research sufficiently to attract private-sector investors and to make the transplant of pig organs and tissues both viable and commercially feasible. The use of pig organs would offer tremendous health, economic, and social benefits by providing sufficient organs to meet the demand, reducing the tens of billions of dollars now spent annually caring for patients with organ failure, and improving their quality of life. PPL projects a market for animal transplants of nearly $6.5 billion within 10 years of launch. In addition, the new technology will create new industries and enable advances in other fields, such as treatment of vascular disease, the science of embryology, and development of animal models for human diseases. PPL sought private-sector partners to share the risk of this research but was told that a genetically altered pig would need to be created first. The parent company of PPL is based in the United Kingdom, but the ATP-funded research and any resulting manufacturing will be carried out in the United States. The University of Washington (Seattle, Wash.) will be subcontracted to assist with the genetic alterations.

For project information:

Karla Gragg, (540) 961-5559
kgragg@ppl-therapeutics.com

ATP Project Manager

Mrunal Chapekar, (301) 975-6846
mrunal.chapekar@nist.gov