Document 0819
 DOCN  M9620819
 TI    Block of HIV-1 infection by a combination of antisense tat RNA and TAR
       decoys: a strategy for control of HIV-1.
 DT    9602
 AU    Chang HK; Gendelman R; Lisziewicz J; Gallo RC; Ensoli B; Laboratory of
       Tumor Cell Biology, National Cancer Institute,; National Institutes of
       Health, Bethesda, MD 20892, USA.
 SO    Gene Ther. 1994 May;1(3):208-16. Unique Identifier : AIDSLINE
       MED/96050942
 AB    The tat gene product (Tat) of HIV-1 is an early regulatory protein
       necessary for viral gene expression and replication. Tat may also play a
       role as an extracellular protein in both HIV-1 replication and
       AIDS-associated disorders such as Kaposi's sarcoma. Thus, Tat represents
       a good target for gene therapy against AIDS. Here we show that when
       vectors expressing antisense tat RNA are transiently transfected into
       CD4+ cells, they block about 70% of HIV-1 replication and inhibit the
       rescue of Tat-defective HIV-1 proviruses by inhibition of Tat protein
       expression and consequent lack of transcriptional activation of the
       HIV-promoter. However, antisense tat vectors cannot block the activity
       of extracellular Tat protein. Another tat inhibitory construct
       (poly-Tat-activation response; TAR) previously suggested to inhibit
       HIV-1 transactivation by sequestering the Tat protein, inhibited the
       activity of extracellular Tat, but like antisense tat RNA did not
       completely block viral gene expression and replication. These results
       suggested that one mode of inhibition is not sufficient to block Tat
       function. However, when the antisense tat and the poly-TAR constructs
       were combined HIV-1 gene expression was completely blocked (94-98%),
       suggesting that a combination of inhibitory genes blocking Tat by
       sequential steps may be a better approach for AIDS gene therapy.
 DE    Acquired Immunodeficiency Syndrome/THERAPY  Antisense Elements
       (Genetics)/GENETICS  Base Sequence  Cell Line  CD4-Positive
       T-Lymphocytes/VIROLOGY  Gene Expression/DRUG EFFECTS  Gene Therapy
       *Genes, tat  Hela Cells  Human  HIV Infections/*PREVENTION &
       CONTROL/VIROLOGY  *HIV-1/DRUG EFFECTS/GENETICS/PHYSIOLOGY  Molecular
       Sequence Data  Plasmids/GENETICS  RNA, Antisense/GENETICS/*PHARMACOLOGY
       Transfection  Virus Replication/DRUG EFFECTS/GENETICS  JOURNAL ARTICLE

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