INHIBITION OF XENOREACTIVE NATURAL ANTIBODY-PRODUCTION BY RETROVIRAL GENE-THERAPY

The major barrier to transplantation across discordant species, such a s from pig to human, is rejection mediated by xenoreactive natural ant ibodies (XNA) that bind the carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (alpha Gal) on donor tissues. This epitope is synthesized by the enzyme glucosyltransferase uridine 5'-diphosphate ose:beta-D-g alactosyl-1.4-N-acetyl-D-glucosaminide alpha(1-3)galactosyltransferase (E.C. 2.4.1.151), pr simply alpha GT. When a functional alpha GT gene was introduced by retroviral gene transfer into bone marrow cells, al pha GaL XNA production in a murine model ceased. Thus, genetic enginee ring of bone marrow may overcome humoral rejection of discordant xenog rafts and may be useful for inducing B cell tolerance.