1. The Multiple Inhibitory Mechanisms of GEM 91®, agagAntisense Phosphorothioate Oligonucleotide, for Human Immunodeficiency Virus Type 1
- Author
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Sudhir Agrawal, Ahmad N. Ali, Randal A. Byrn, Béla Papp, Koushi Yamaguchi, and Dezhen Zhang
- Subjects
DNA Replication ,Transcription, Genetic ,Anti-HIV Agents ,viruses ,Immunology ,HIV Infections ,Biology ,Virus Replication ,Virus ,Oligodeoxyribonucleotides, Antisense ,Zidovudine ,Virion binding ,Viral entry ,Virology ,Gene expression ,medicine ,Humans ,RNA, Messenger ,Cells, Cultured ,Oligonucleotide ,Virus Assembly ,Drug Resistance, Microbial ,Oligonucleotides, Antisense ,Thionucleotides ,Blotting, Northern ,Molecular biology ,Reverse transcriptase ,Infectious Diseases ,Viral replication ,HIV-1 ,RNA, Viral ,medicine.drug - Abstract
GEM 91 (gene expression modulator) is a 25-mer oligonucleotide phosphorothioate complementary to the gag initiation site of HIV-1. GEM 91 has been studied in various in vitro cell culture models to examine inhibitory effects on different stages of HIV-1 replication. Experiments were focused on the binding of virions to the cell surface, inhibition of virus entry, reverse transcription (HIV DNA production), inhibition of steady state viral mRNA levels, inhibition of virus production from chronically infected cells, and inhibition of HIV genome packaging within virions. Experiments were also performed in vitro in an attempt to generate strains of HIV with reduced sensitivity to GEM 91. We observed sequence-dependent inhibition of virus entry/reverse transcription and a reduction in steady state viral RNA levels. We also observed sequence-independent inhibition of virion binding to cells and inhibition of virus production by chronically infected cells. Using in vitro methods that were successful in generating HIV strains with reduced sensitivity to AZT, we were unable to generate strains with reduced sensitivity to GEM 91.
- Published
- 1997