Document 0119
 DOCN  M9580119
 TI    Inhibition of HIV-1 Tat-mediated LTR transactivation and HIV-1 infection
       by anti-Tat single chain intrabodies.
 DT    9506
 AU    Mhashilkar AM; Bagley J; Chen SY; Szilvay AM; Helland DG; Marasco WA;
       Department of Pathology, Dana-Farber Cancer Institute, Harvard; Medical
       School, Boston, MA 02115, USA.
 SO    EMBO J. 1995 Apr 3;14(7):1542-51. Unique Identifier : AIDSLINE
       MED/95246747
 AB    Genes encoding the rearranged immunoglobulin heavy and light chain
       variable regions of anti-HIV-1 Tat, exon 1 or exon 2 specific monoclonal
       antibodies have been used to construct single chain intracellular
       antibodies 'intrabodies' for expression in the cytoplasm of mammalian
       cells. These anti-Tat single chain intrabodies (anti-Tat sFvs) are
       additionally modified with a C-terminal human C kappa domain to increase
       cytoplasmic stability and/or the C-terminal SV40 nuclear localization
       signal to direct the nascent intrabody to the nuclear compartment,
       respectively. The anti-Tat sFvs with specific binding activity against
       the N-terminal activation domain of Tat, block Tat-mediated
       transactivation of HIV-1 LTR as well as intracellular trafficking of Tat
       in mammalian cells. As a result, the transformed lymphocytes expressing
       anti-Tat sFvs are resistant to HIV-1 infection. Thus, these studies
       demonstrate that stably expressed single chain intrabodies and their
       modified forms can effectively target molecules in the cytoplasm and
       nuclear compartments of eukaryotic cells. Furthermore, these studies
       suggest that anti-Tat sFvs used either alone or in combination with
       other genetically based strategies may be useful for the gene therapy of
       HIV-1 infection and AIDS.
 DE    Animal  *Antibodies, Monoclonal/BIOSYNTHESIS  Antigenic
       Determinants/*ANALYSIS  Base Sequence  Cell Line  Cell Line, Transformed
       Cercopithecus aethiops  DNA Primers  Exons  Gene Products,
       tat/IMMUNOLOGY/*METABOLISM  Gene Rearrangement  Genes, Immunoglobulin
       Hela Cells  Human  HIV Long Terminal Repeat/*PHYSIOLOGY
       HIV-1/GENETICS/*PHYSIOLOGY  Immunoglobulin Variable
       Region/BIOSYNTHESIS/GENETICS  Immunoglobulins,
       Heavy-Chain/BIOSYNTHESIS/GENETICS  Immunoglobulins,
       Light-Chain/BIOSYNTHESIS/GENETICS  Kidney  Mice  Mice, Inbred BALB
       C/IMMUNOLOGY  Molecular Sequence Data  Polymerase Chain Reaction
       Recombinant Proteins/IMMUNOLOGY/METABOLISM  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  T-Lymphocytes  Transfection  JOURNAL
       ARTICLE

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