Inhibition of human interferon-gamma expression by antisense oligodeoxynucleotides

• Published in: Journal of leukocyte biology 1994-02, Vol.55 (2), p.169-174
• Main Authors: Boeve, Christine M.A., De Ley, Marc
• Format: Article
• Language: English
• Subjects: Base Sequence; Biological and medical sciences; Cells, Cultured; cytokine; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression - drug effects; Humans; hybrid arrested translation; Interferon-gamma - biosynthesis; Kinetics; lymphocytes; Lymphocytes - drug effects; Lymphocytes - immunology; Lymphocytes - metabolism; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Oligonucleotides, Antisense - pharmacology; Structure-Activity Relationship; Time Factors
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/jlb.55.2.169

We investigated 12 antisense oligodeoxynucleotides, complementary to different regions of the human interferon‐γ (HuIFN‐γ) gene, for their ability to inhibit HuIFN‐γ 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. J. Leukoc. Biol. 55: 169–174; 1994.