Document 0854
 DOCN  M95A0854
 TI    Antitat gene therapy: a candidate for late-stage AIDS patients.
 DT    9510
 AU    Lisziewicz J; Sun D; Lisziewicz A; Gallo RC; Laboratory of Tumor Cell
       Biology, National Cancer Institute,; National Institutes of Health,
       Bethesda, MD 20892-4255, USA.
 SO    Gene Ther. 1995 May;2(3):218-22. Unique Identifier : AIDSLINE
       MED/95339008
 AB    Antitat is an autoregulated gene expressing an inhibitory RNA with dual
       function: it sequesters the Tat protein by polymeric-TAR and blocks the
       translation of the Tat messenger RNA by antisense-Tat. Using human T
       cell lines and peripheral blood lymphocytes as the in vitro target, we
       have previously shown that antitat is an effective long-term suppressor
       of HIV-1, including 'field' isolates. To assess the efficacy of this
       inhibitory gene better in the setting of an infected individual with
       late-stage AIDS, we examined its antiviral activity in an in vivo
       established infection. Peripheral blood mononuclear cells isolated from
       AIDS patients were transduced with replication defective retroviral
       vectors carrying the antitat gene. In the absence of cell selection, the
       antitat gene blocked virus replication and allowed infected CD4+ T cells
       to expand in culture. These results suggest that antitat gene therapy
       may be beneficial to block HIV-1 replication and reconstitute the immune
       system of late-phase AIDS patients. We introduced a new parameter, CRF,
       which defines the effectiveness of the ex vivo gene therapy treatment of
       AIDS patients. Antitat treatment was efficient in cells of all patients
       regardless of viral quasispecies, however, it was most potent in
       severely immunocompromised individuals.
 DE    Acquired Immunodeficiency Syndrome/IMMUNOLOGY/*THERAPY  CD4 Lymphocyte
       Count  CD4-Positive T-Lymphocytes/IMMUNOLOGY/*VIROLOGY  Gene Products,
       tat/METABOLISM  Gene Therapy/METHODS  *Gene Transfer  Genes,
       tat/*GENETICS  Genetic Vectors/GENETICS  Human  HIV Core Protein
       p24/BIOSYNTHESIS  HIV Infections/IMMUNOLOGY/THERAPY  HIV Long Terminal
       Repeat/*GENETICS  HIV-1/*GENETICS/PHYSIOLOGY  Leukocytes, Mononuclear
       Lymphocyte Transformation  Retroviridae/GENETICS  RNA,
       Antisense/GENETICS  Virus Replication/GENETICS  JOURNAL ARTICLE

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