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Science 18 September 1998:
Vol. 281. no. 5384, pp. 1845 - 1847
DOI: 10.1126/science.281.5384.1845
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Reports

Inhibition of Xenoreactive Natural Antibody Production by Retroviral Gene Therapy

Jennifer L. Bracy, David H. Sachs, John Iacomini *

The major barrier to transplantation across discordant species, such as from pig to human, is rejection mediated by xenoreactive natural antibodies (XNA) that bind the carbohydrate epitope Galalpha 1-3Galbeta 1-4GlcNAc-R (alpha Gal) on donor tissues. This epitope is synthesized by the enzyme glucosyltransferase uridine 5'-diphosphate galactose:beta -D-galactosyl-1,4-N-acetyl-D-glucosaminide alpha (1-3)galactosyltransferase (E.C. 2.4.1.151), or simply alpha GT. When a functional alpha GT gene was introduced by retroviral gene transfer into bone marrow cells, alpha Gal XNA production in a murine model ceased. Thus, genetic engineering of bone marrow may overcome humoral rejection of discordant xenografts and may be useful for inducing B cell tolerance.

J. L. Bracy, Cellular and Molecular Biology Program, Allegheny University of the Health Sciences, 2900 Queen Lane, Philadelphia, PA 19129, USA, and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149-5210, 13th Street, Boston, MA 02129, USA. D. H. Sachs and J. Iacomini, Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149-5210, 13th Street, Boston, MA 02129, USA.
*   To whom correspondence should be addressed. E-mail: iacomini{at}helix.mgh.harvard.edu

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