Inhibition of Xenoreactive Natural Antibody Production by Retroviral Gene Therapy

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Science  18 Sep 1998:
Vol. 281, Issue 5384, pp. 1845-1847
DOI: 10.1126/science.281.5384.1845

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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 Galα1-3Galβ1-4GlcNAc-R (αGal) on donor tissues. This epitope is synthesized by the enzyme glucosyltransferase uridine 5′-diphosphate galactose:β-d-galactosyl-1,4-N-acetyl-d-glucosaminide α(1-3)galactosyltransferase (E.C., or simply αGT. When a functional αGT gene was introduced by retroviral gene transfer into bone marrow cells, αGal 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.

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