       Document 0816
 DOCN  M9620816
 TI    Inhibition of HIV-1 in CEM cells by a potent TAR decoy.
 DT    9602
 AU    Lee SW; Gallardo HF; Gaspar O; Smith C; Gilboa E; Program of Molecular
       Biology, Memorial Sloan-Kettering Cancer; Center, New York, NY 10021,
       USA.
 SO    Gene Ther. 1995 Aug;2(6):377-84. Unique Identifier : AIDSLINE
       MED/96002913
 AB    TAR decoys are short RNA oligonucleotides, corresponding to the HIV TAR
       sequence, which inhibit HIV expression and replication by blocking the
       binding of the HIV regulatory protein Tat to the authentic TAR region.
       In previous studies, TAR decoys expressed from a tRNA polIII promoter
       were moderately effective at inhibiting HIV in isolated human T cell
       lines and less effective at inhibiting HIV in peripheral blood CD4+ T
       cells. In this study, a series of modifications was introduced into the
       tRNA expression cassette in order to improve their effectiveness. These
       modifications included the addition of sequences which are predicted to
       have stem-loop secondary structures and addition of a wild-type tRNA
       processing site. TAR decoy RNA expressed in CEM cells from modified
       tRNA-based expression cassettes yielded five- to 20-fold more TAR
       transcripts than unmodified tRNA-based expression cassettes. HIV
       replication, as measured by a flow cytometric method to quantify
       intracellular viral p24 expression, was significantly reduced in
       polyclonal populations of CEM cells expressing a modified tRNA-TAR
       transcript that contains a wild-type tRNA processing site and stem-loops
       5' and 3' to the TAR sequence. Similar modifications to the tRNA
       expression cassette also increased the intracellular concentration of a
       random test oligonucleotide, indicating that this improved expression
       system may also be useful for antisense and ribozyme based gene
       inhibition strategies.
 DE    Antiviral Agents/*PHARMACOLOGY  Base Sequence  Cell Line  Cells,
       Cultured  Comparative Study  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY/VIROLOGY  Gene Expression  Gene Products,
       tat/*METABOLISM  *Genetic Vectors  Human  HIV Core Protein
       p24/ANALYSIS/BIOSYNTHESIS  HIV-1/DRUG EFFECTS/GENETICS/*PHYSIOLOGY
       Molecular Sequence Data  Moloney Leukemia Virus/GENETICS  Nucleic Acid
       Conformation  Oligodeoxyribonucleotides
       Oligoribonucleotides/METABOLISM/*PHARMACOLOGY  Promoter Regions
       (Genetics)  *Regulatory Sequences, Nucleic Acid  RNA,
       Catalytic/METABOLISM  RNA, Transfer/*BIOSYNTHESIS/CHEMISTRY  Support,
       U.S. Gov't, P.H.S.  T-Lymphocytes/IMMUNOLOGY/*VIROLOGY  Transcription,
       Genetic  *Transfection  Tumor Cells, Cultured  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).

