Inhibition of human interferon-gamma biosynthesis by an antisense RNA-expressing vector.
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.
Boeve
C M
CM
Laboratory for Biochemistry, Katholieke Universiteit Leuven, Heverlee, Belgium.
Wyngaerd
A V
AV
De Ley
M
M
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D017931:DNA Primers; D005822:Genetic Vectors; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D016372:RNA, Antisense / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection
D017931:DNA Primers; D016372:RNA, Antisense; D012333:RNA, Messenger; D007371:Interferon-gamma