Document 0038
 DOCN  M9460038
 TI    A Rev-inducible mutant gag gene stably transferred into T lymphocytes:
       an approach to gene therapy against human immunodeficiency virus type 1
       infection.
 DT    9408
 AU    Smythe JA; Sun D; Thomson M; Markham PD; Reitz MS Jr; Gallo RC;
       Lisziewicz J; Laboratory of Tumor Cell Biology, National Cancer
       Institute,; National Institutes of Health, Bethesda, MD 20892.
 SO    Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3657-61. Unique Identifier :
       AIDSLINE MED/94224800
 AB    One strategy for somatic gene therapy for human immunodeficiency virus
       type 1 (HIV-1) infection is based on the regulated expression of
       dominant negative mutants of the HIV-1 gag gene. To limit expression of
       the mutant Gag polypeptide to HIV-1-infected cells, we have constructed
       a replication-defective retroviral vector that contains a Rev-responsive
       element. By using this construct we have obviated problems that can be
       associated with constitutive expression of an exogenous gene, an
       important step toward developing a human therapy. In uncloned T
       lymphocytes infected (transduced) with this retroviral construct, HIV-1
       replication was inhibited by 94% with a concomitant decrease in the
       cytopathic effects of the virus. In addition, simian immunodeficiency
       virus (SIV) replication was also shown to be significantly inhibited,
       suggesting that this mutant Gag protein may have antiviral efficacy
       against a broad range of primate lentiviruses and that an SIV/macaque
       model can be used for further in vivo studies. These results have
       important implications in assessing the potential of somatic gene
       therapy in the treatment of HIV-1 infection.
 DE    Amino Acid Sequence  Base Sequence  Gene Expression Regulation, Viral
       Gene Therapy  *Genes, gag  *Genes, rev  Hela Cells  Human  HIV
       Infections/*THERAPY  HIV-1/GROWTH & DEVELOPMENT/GENETICS  In Vitro
       Molecular Sequence Data  Mutation  RNA, Viral/GENETICS  Support,
       Non-U.S. Gov't  SIV/GROWTH & DEVELOPMENT/GENETICS
       T-Lymphocytes/*MICROBIOLOGY  Transduction, Genetic  Virus Replication
       JOURNAL ARTICLE

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