AN OLIGONUCLEOTIDE BLOCKS INTERFERON-GAMMA SIGNAL-TRANSDUCTION

Interferon (IFN)-gamma is an important mediator of transplant graft re jection. It induces endothelial cell expression of HLA-DR and intercel lular adhesion molecule-1, which render transplant grafts more suscept ible to rejection by the host. Oligonucleotide 5'-GGG GTT GGT TGT GTT GGG TGT TGT GT-RNH2 (oligo I) blocks multiple IFN-gamma effects in hum an K562 cell cultures. A systematic approach revealed that oligo I has a novel, and potentially important, mode of action-it blocks the bind ing of IFN-gamma to its receptor, thus preventing activation of the IF N-gamma signal transduction pathway. The results are consistent with a n aptamer mechanism of action, because oligo I exerts its inhibitory e ffects by interacting with protein, not intracellular nucleic acid tar gets, such as mRNA or genomic DNA.