SBIR-STTR Award

Severe shortages of human donor organs and cells for transplantation have resulted in great interest in the use of pigs as organ donors. Associated with the clear benefits of xenotransplantation is the risk of infection of the recipient with porcine microorganisms introduced along with the donor organ. Of primary concern are those organisms that can be transferred in a latent state in the xenograft recipient. Retroviruses fall into this category. Endogenous retroviruses form a normal part of the genomic DNA of all pig cells and thus can not be removed by techniques such as barrier derivation that clears other microorganisms. As such, porcine endogenous retroviruses (PERV) represent a particularly problematic safety concern for xenotransplantation. All breeds of pig tested to date produce PERV capable of infecting human cells. BioTransplant has identified a particular haplotype of animals within its inbred miniature swine herd that does not produce PERV capable of infecting human cells. Consequently these animals might represent a source of safer organs for xenotransplantation. Characterization of these animals is proposed in this Phase I application. PROPOSED COMMERCIAL APPLICATIONS: The critical worldwide shortage of donor organs and ever-increasing waiting lists for organ recipients have long been recognized. Xenotransplantation is a long-term solution to this chronic shortage. A roadblock to the acceptance of this strategy has been concern about the risk for transmission of pathogens from the donor to the host. BioTransplant has developed a herd of miniature swine that do not produce porcine endogenous retrovirus capable of infecting human cells. This quality provides a significant commercial advantage for their use as the herd of choice for xenotransplantation

Xenotransplantation has the potential to provide organs for the 60,000 patients waiting for transplants, and to therefore eliminate the 4,000 deaths occur every year due to a lack of donor organs. For the safety of the general public, it is essential that the organs be supplied with a minimized microbiological burden to prevent new zoonotic infections spreading in the human population. The innovative aim of this research proposal is to develop the DID haplotype miniature swine as the donor animal of choice for xenotransplantation. These animals are unique amongst all strains of pig tested due to their absence of infectious human-tropic pig endogenous retrovirus (PERV). PERV, and other latent organisms such as herpesviruses, represent a particular microbiological safety concern for xenotransplantation. The studies proposed seek to determine the genetic basis for the lack of human-tropic PERV. Once defined, the information may facilitate the breeding of other breeds of PERV-free animals. Pig herpesviruses are another serious safety concern for xenotransplantation. Studies seek to investigate the biology of a recently discovered porcine gamma-herpesvirus. The development of technologies that enable both the control and eradication of this agent are proposed. PROPOSED COMMERCIAL APPLICATION: In excess of 60,000 people are currently waiting for organ transplants due to a lack of donor organs. Xenotransplantation has the potential to relieve this shortage. The unique absence of human-tropic PERV in the inbred D/D haplotype miniature swine make it ideal to be developed as the animal of choice to supply the tissues used for all xenotransplants.