Inhibition of human interferon-gamma biosynthesis by an antisense RNA-expressing vector

• Published in: Molecular pharmacology Vol. 49; no. 1; pp. 58 - 62
• Main Authors: Boeve, C M, Wyngaerd, A V, De Ley, M
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.01.1996
• Subjects: Animals; Base Sequence; Cell Line; CHO Cells; Cricetinae; DNA Primers; Genetic Vectors; Humans; Interferon-gamma - antagonists & inhibitors; Interferon-gamma - biosynthesis; Interferon-gamma - genetics; Mice; Molecular Sequence Data; RNA, Antisense - genetics; RNA, Antisense - pharmacology; RNA, Messenger - genetics; Transfection
• ISSN: 0026-895X; 1521-0111

We applied antisense RNA technology for reducing the level of human IFN-gamma (HuIFN-gamma) expression. An antisense RNA vector containing the full-length HuIFN-gamma cDNA in the opposite orientation was electroporated into cells constitutively producing very high levels of the cytokine. Approximately 53% of the resulting clones exhibited a specific HuIFN-gamma inhibition of an average of 95.5%. The results of reverse transcription-polymerase chain reaction and Northern blot analyses revealed that the antisense effect originated from a specific reduction of the targeted mRNA caused by antisense RNA expression. This very effective antisense RNA strategy can have possible therapeutic applications in treating diseases where HuIFN-gamma is known to play a negative role, such as in certain autoimmune diseases.