INHIBITION OF HUMAN INTERFERON-GAMMA EXPRESSION BY ANTISENSE OLIGODEOXYNUCLEOTIDES

We investigated 12 antisense oligodeoxynucleotides, complementary to different regions of the human interferon-gamma (HuIFN-gamma) gene, for their ability to inhibit HuIFN-gamma production in cultures of single donor total leukocytes or lymphocytes (95% purity). Out of seven oligomers, specific for a sequence including the translation initiation codon, 15 to 21 nucleotides long, the one resulting in the greatest inhibition was the 16-mer. An inhibitory effect of 90% could be achieved when the oligomer was added to cultures of lymphocytes in separate doses. Three other 16-mers, complementary to a sequence in the 5' noncoding region, in the coding region, or at the donor splice junction of the third intron respectively, were inhibitory to a lesser extent. Two 16-mers, one complementary to a sequence at the donor splice junction of the second intron and one specific for a sequence in the 3' untranslated region, showed no effect.