Open Competition 2 - Biotechnology

Preventing Porcine Endogenous Retrovirus Transmission in Xenograft Tissues

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

• Project Performance Period: 7/1/2003 - 6/30/2006
• Total project (est.): $2,657,192.00
• Requested ATP funds: $1,968,290.00

Xenotransplantation - therapeutic transfer of organs or tissues from one species to another - may be the most promising solution for overcoming the critical shortage of human organs and tissues available for transplantation. Pigs generally are accepted as being the most suitable source of organs for xenotransplantation into humans, but xenografts - the organs or tissues actually transplanted from pigs - present two serious challenges. One is the rejection of grafts by the human immune system. With prior ATP funding, Revivicor (formerly PPL Therapeutics, Inc.) succeeded in cloning pigs that lack both copies of the gene responsible for making (alpha)1,3-galactosyltransferase ((alpha)1,3GT). This will enable tissues derived from these "double knockout" pigs to have a much higher probability of preventing rejection by humans. The other challenge is the potential transmission risk associated with pig endogenous retrovirus (PERV) infection in patients receiving xenografts. To address this problem, Revivicor proposes to genetically modify (alpha)1,3GT double knockout pigs so the resultant pigs will not produce any functional PERV particles, including those that may arise as a result of recombination events. The technological approach is to develop pigs that are incapable of replicating or propagating PERV or its derivatives. This project holds significant risk because no such mammals have ever been made or described. The current capital-funding climate for biotechnology companies is poor, and the application of this technology to PERV is too early-stage to attract private investment. Success of this project is expected to facilitate regulatory approval of xenotransplants from pigs for human use and pave the way for a readily available supply of donor organs and tissues. Initially, a cure for type 1 diabetes would be attempted, and then definitive treatments for kidney, heart, and liver transplants could arise, improving the quality of life for patients and saving billions of dollars each year in health care costs that now must be spent on patient maintenance. A new xenotransplantation industry providing extensive economic benefits would likely develop. In time, this technology also could lead to the genetic engineering of disease-resistant animals for agriculture.

For project information:

David Ayares, (540) 961-5559
missing

ATP Project Manager

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