Xenotransplantation and Gene Therapy - Christopher G. McGregor

Overview

Xenotransplantation

For all of its success, transplantation has only a small fraction of the impact that it might have on medicine. This limitation is not medical or scientific but rather societal – there is a severe and very urgent shortage of donors. More than 90,000 Americans are currently on the waiting list for transplantation with only 25,000 organs available annually. Seventeen people die each day while awaiting transplant.

One potential approach to address the donor shortage is xenotransplantation, which involves transplanting living organs, tissues and cells from one species to another. The idea of conducting animal-to-human transplants is not a new one. Indeed, xenotransplantation has been tried at various times during the past 95 years. Recent scientific study has revealed that there exist specific molecular hurdles to carrying out pig-to-human xenografts and that these hurdles can be addressed in a definitive manner by the genetic engineering of animals. The success of this endeavor has stimulated the imagination of many in the field of transplantation. Research studies include:

• Genetic Engineering Research. As part of the xenotransplantation research program, Mayo Clinic scientists have been studying the human immune system and genetically engineering pig organs so that they do not trigger the standard human immune response that destroys organs. To accommodate this research, Mayo Clinic has constructed a specialized, high-tech transgenic facility.
• Preclinical Research. Mayo Clinic transplant scientists and physicians are studying pig xenotransplantation using transgenic pig donors. The preclinical research is aimed at developing a clinical xenotransplantation program at Mayo.
• Immunosuppression and Rejection. The principal focus in the xenotransplantation laboratory is optimization of immunosuppression following xenotransplantation with specific studies on the pathophysiology of vascular rejection.

Gene therapy

Gene therapy, defined as the treatment of disease using the transfer of genetic material into tissues in vivo, has emerged as a potential approach to many diseases that are inadequately treated with current therapy. Transplantation may be an ideal setting for gene therapy as the donor organ is available for genetic modification between the times of procurement and implantation when the organ is not required to function. The potential targets for effective gene therapy include the treatment of acute and chronic rejection of the transplanted heart. In the Mayo laboratory, funded by the National Institutes of Health, new systems of delivering genes efficiently to the transplanted heart are being developed as well as studies on the effects of successful delivery of novel gene products. These gene therapy studies are in collaboration with the new Molecular Medicine Program at Mayo Rochester.