Document 0368
 DOCN  M9490368
 TI    Antisense oligodeoxynucleotide phosphorothioate complementary to Gag
       mRNA blocks replication of human immunodeficiency virus type 1 in human
       peripheral blood cells.
 DT    9411
 AU    Lisziewicz J; Sun D; Weichold FF; Thierry AR; Lusso P; Tang J; Gallo RC;
       Agrawal S; Laboratory of Tumor Cell Biology, National Cancer Institute,;
       National Institutes of Health, Bethesda, MD 20892.
 SO    Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):7942-6. Unique Identifier :
       AIDSLINE MED/94336663
 AB    Gene-expression modulator 91 (GEM91) is a 25-nt antisense
       oligodeoxynucleotide phosphorothioate complementary to the Gag mRNA of
       human immunodeficiency virus type 1 (HIV-1). Cellular uptake and
       intracellular distribution of GEM91 within cells suggest that this
       oligomer is readily available for antisense activity. GEM91 inhibited
       HIV-1 replication in a dose-dependent and sequence-specific manner. In a
       comparative study, 2 microM GEM91 was as effective as 5 microM
       3'-azido-3'-deoxythymidine in blocking virus replication during the
       28-day treatment of an HIV-1-infected T-cell line. GEM91 also completely
       inhibited (> 99%) the growth of three different HIV-1 isolates in
       primary lymphocytes and prevented the cytopathic effect of the virus in
       primary CD4+ T cells. Similarly, treatment with GEM91 for 3 weeks of
       HIV-1/BaL-infected primary macrophages blocked virus replication. Based
       on GEM91 anti-HIV-activity, safety, and pharmacokinetic profile in
       animals, a clinical trial was started using this compound as an
       antisense oligonucleotide drug for the treatment of the acquired
       immunodeficiency syndrome.
 DE    Antigens, CD/BIOSYNTHESIS  Antigens, CD4/BIOSYNTHESIS  Antigens,
       CD8/BIOSYNTHESIS  Antiviral Agents/*TOXICITY  Base Sequence  Biological
       Transport  Cell Line  Cells, Cultured  Flow Cytometry  Gene Products,
       gag/*BIOSYNTHESIS  Genes, gag  Human  HIV-1/*DRUG EFFECTS/PHYSIOLOGY
       Kinetics  Lymphocytes/CYTOLOGY/DRUG EFFECTS/*MICROBIOLOGY
       Macrophages/CYTOLOGY/*MICROBIOLOGY  Molecular Sequence Data
       Oligonucleotides, Antisense/PHARMACOKINETICS/*TOXICITY  RNA,
       Messenger/*DRUG EFFECTS  Thionucleotides/PHARMACOKINETICS/*TOXICITY
       Virus Replication/*DRUG EFFECTS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).