“This is an important study because past research has shown that PERV released from some pig cells can infect human cells in-vitro,” said Clive Patience Ph.D. Associate Director, Immerge BioTherapeutics Inc., and lead investigator of this study. “Although the use of porcine tissues has tremendous potential to alleviate the shortage of donor organs, the inadvertent transmission of PERV to organ recipients has been a major safety concern.”
In this study, Dr. Patience et al. characterize three sub-classes of PERV (A, B and C) that are found in the herd of inbred miniature swine. Following repeat testing on up to four occasions, results showed that families of animals could be identified that possesses a consistent non-transmitting phenotype. In addition, it is possible that replication competent PERV-A viruses may not be present in the genomic DNA of these miniature swine, as only recombinations between PERV-A and PERV-C were identified within infected human cells.
The need to find new sources for donor organs is a critical one, and the demand is growing each day. There are currently more than 79,000 people on the U.S. transplant waiting list and potentially an equal number that never make the list because of the strict criteria needed to ensure that precious organs go to those candidates that are most likely to be successful recipients. More than 16 people die each day waiting for a transplant. Xenotransplantation may offer new hope for these people.
Another Milestone Reached
In January, Immerge BioTherapeutics and the University of Missouri reported in the on-line edition of the journal Science that they had knocked out a gene from this same strain of miniature swine that produces a key sugar molecule (a1,3-galactosyltransferase or GGTA) responsible for triggering the vigorous rejection process that historically occurs following xenotransplantation. The aggressive (hyperacute) rejection response happens when human antibodies attach to sugar molecules on the surface of the transplanted pig organ’s cells. Once they attach, the antibodies kill the cells. With this gene eliminated, there is no sugar for the antibodies to attach to, so the rejection cascade cannot begin.
“These two studies show that animals within this herd of miniature swine have the potential to be an ideal source for xenotransplantation,” said Julia Greenstein, Ph.D., CEO and President, Immerge BioTherapeutics Inc. “While there is still much work to be done, we are very excited that we have moved the science of xenotransplantation forward several steps toward clinical application.”
Immerge BioTherapeutics was formed in September 2000, as a joint venture between Novartis Pharma AG and BioTransplant Incorporated. The company, which began operations in January 2001, focuses its research efforts toward developing therapeutic applications for xenotransplantation. The name of the company derives from its use of immunology to address the challenges of conducting transplants between species.
Journal
Journal of Virology