Fu Z F, Wickstrom E, Jiang M, Corisdeo S, Yang J, Dietzschold B, Koprowski H
Department of Microbiology and Immunology, Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Antisense Nucleic Acid Drug Dev. 1996 Summer;6(2):87-93. doi: 10.1089/oli.1.1996.6.87.
To develop antirabies virus-specific agents, eight oligodeoxynucleotides (ODN) complementary to either rabies virus genomic RNA (negative polarity) or rabies virus transcripts (mRNA) were synthesized and tested for their activity to inhibit rabies virus infection in cell cultures. It was found that the ODN RH+1 complementary to rabies virus genomic RNA blocked almost completely rabies virus infection at concentrations as low as 2 microM, whereas ODN complementary to viral transcripts did poorly even at concentrations as high as 20 microM. The antigenomic ODN also has the ability to inhibit cell-to-cell spread of rabies virus, which is an indicator for protection of rabies virus infection in vivo. These results indicate that ODN complementary to rabies virus genomic RNA have strong ability to inhibit rabies virus infection in cell culture and may have the potential to be used for therapy in clinical rabies.
为开发抗狂犬病病毒特异性药物,合成了8种与狂犬病病毒基因组RNA(负链)或狂犬病病毒转录本(mRNA)互补的寡脱氧核苷酸(ODN),并检测了它们在细胞培养物中抑制狂犬病病毒感染的活性。结果发现,与狂犬病病毒基因组RNA互补的ODN RH+1在低至2微摩尔的浓度下几乎能完全阻断狂犬病病毒感染,而与病毒转录本互补的ODN即使在高达20微摩尔的浓度下效果也很差。反基因组ODN也有抑制狂犬病病毒细胞间传播的能力,这是体内保护狂犬病病毒感染的一个指标。这些结果表明,与狂犬病病毒基因组RNA互补的ODN在细胞培养中有很强的抑制狂犬病病毒感染的能力,可能有潜力用于临床狂犬病的治疗。