Abstract:
The use of antisense oligomers has been shown to be effective in inhibiting replication of another retrovirus, human immunodeficiency virus (HIV). The purpose of this study was to investigate antisense oligomers which may be useful in inhibiting MMTV infection and/or replication. We have synthesized five 20-mer oligomers which are complementary to the MMTV proviral DNA. The targets chosen were based on previously published work for HIV. The effect of the oligomers on reducing initial infection of a normal mouse mammary epithelial line (NMuMG) with MMTV is determined by using immunofluorescent cell staining to the GP52/36 viral membrane proteins to measure the infection centers. A chronically MMTV-infected cell line (Mm5MT) is used to determine the effect of the oligomers on viral production. At days 1, 3 and 5 after treatment of cell cultures with the various antisense oligomers, the production and release of MMTV into the media are measured by competition ELISA using an anti-GP52/36 serum. The level of reverse transcriptase activity in each culture condition is also determined daily by RDDP assay on days 1-6 after treatment. Initial results indicate that inhibition of MMTV replication by antisense oligomers is dose- and site-dependent and ranges from 20-90% for the culture condition used.
Keywords: Animal Cell Line Dose-Response Relationship, Drug Mammary Tumor Viruses, Mouse/*DRUG EFFECTS Mice Oligonucleotides, Antisense/*PHARMACOLOGY Tumor Cells, Cultured/*MICROBIOLOGY Virus Replication/*DRUG EFFECTS ABSTRACT 912130
M91C4076
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