Genetic manipulation in pigs.
OBJECTIVE
Recent developments in the field of genetic engineering have made it possible to add, delete or exchange genes from one species to another. This technology has special relevance to the field of xenotransplantation, in which the elimination of a species-specific disparity could make the difference between success and failure of an organ transplant. This review focuses on developments in both the techniques and applications of genetically modified animals.


RESULTS
Advances have been made using existing techniques for genetic modifications of swine and in the development of new, emerging technologies, including enzymatic engineering and the use of small interfering RNA. Applications of the modified animals have provided evidence that genetically modified swine have the potential to overcome both physiologic and immunologic barriers that have previously impeded this field. The use of alpha-1,3-galactosyltransferase gene-knockout animals as donors have shown marked improvements in xenograft survivals.


CONCLUSIONS
Techniques for genetic engineering of swine have been directed toward avoiding naturally existing cellular and antibody responses to species-specific antigens. Organs from genetically engineered animals have enjoyed markedly improved survivals in nonhuman primates, especially in protocols directed toward the induction of tolerance, presumably by avoiding immunization to new antigens.
Sachs
David H
DH
Massachusetts General Hospital, Transplantation Biology Research Center, Boston, Massachusetts 02129, USA. david.sachs@tbrc.mgh.harvard.edu
Galli
Cesare
C
D000818:Animals; D030801:Animals, Genetically Modified; D005700:Galactosyltransferases / Q000172:deficiency / Q000235:genetics*; D055786:Gene Knockout Techniques; D005821:Genetic Techniques; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000235:genetics* / Q000276:immunology; D006801:Humans; D016377:Organ Transplantation; D013045:Species Specificity; D013552:Swine / Q000235:genetics* / Q000276:immunology; D023001:Transplantation Tolerance / Q000235:genetics; D014183:Transplantation, Heterologous; D014312:Trisaccharides / Q000276:immunology
D014312:Trisaccharides; C076569:alpha-galactosyl epitope; D005700:Galactosyltransferases; C530267:alpha-1,3-galactosyltransferase 1, porcine